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Ibrahim A, Allam J, Rockey DC. Octreotide therapy in patients with a left ventricular assist device and bleeding gastrointestinal angiodysplasias. Am J Med Sci 2025:S0002-9629(25)00956-5. [PMID: 40086695 DOI: 10.1016/j.amjms.2025.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 03/05/2025] [Accepted: 03/10/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND Angiodysplasias commonly develop in patients with left ventricular assist devices (LVADs) and often bleed recurrently. Whether octreotide reduces the burden of angiodysplasia or the frequency of bleeding in these patients is controversial. Hence, we aimed to study the effect of long-acting octreotide on angiodysplasia bleeding in LVAD patients. METHODS Between May 2012 and December 2023, 65 patients with LVAD and angiodysplasia were identified at our tertiary care medical center. Of those, 33 patients received octreotide therapy. Complete clinical data were abstracted from the medical record, and outcomes pre and post octreotide therapy were examined. RESULTS In 33 patients (61 ± 8 years old and 9 women) who received long-acting octreotide for recurrent angiodysplasia bleeding that failed to respond to endoscopic therapy, the small intestine was the most common site involved. Prior to octreotide, patients received an average of 2.0 ± 3.0 units/month of PRBCs over an average of 16 months, which decreased to 0.5 ± 0.8 units/month over 31 months on therapy. Over an average period of 31 months on octreotide therapy, GI bleeding events and the number of endoscopic therapies per month decreased from 0.4 ± 0.2 to 0.1 ± 0.2 (p = 0.01) and from 0.7 ± 0.8 to 0.1 ± 0.2 (p = 0.001), respectively. Finally, hemoglobin and hematocrit levels increased over the 31 month follow-up period while on octreotide therapy. CONCLUSION In patients with an LVAD and recurrent angiodysplasia bleeding, octreotide appeared to reduce the number of GI bleeding events, the need for GI endoscopic therapies, and the frequency of PRBC transfusions.
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Affiliation(s)
- Ahmed Ibrahim
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Jad Allam
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Don C Rockey
- Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC 29425, USA.
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2
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Bhattarai S, Algarin Perneth S, Padilla Zambrano H, Leggett CL. Clinical approach to the diagnosis and management of small bowel bleeding. Minerva Med 2025; 116:31-42. [PMID: 39328002 DOI: 10.23736/s0026-4806.24.09361-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2024]
Abstract
The diagnosis and management of small bowel bleeding (SBB) can be a clinical challenge. Advances in video capsule endoscopy, balloon-assisted enteroscopy, and multiphasic computed tomography allow for localization and therapeutic intervention. Etiologies of SBB including vascular, neoplastic, and inflammatory conditions are associated with age and comorbidities. The present review highlights terminologies that describe SBB, provides a differential diagnosis for bleeding etiologies, and summarizes a clinical approach to managing this condition.
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Affiliation(s)
- Sanket Bhattarai
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | | | - Cadman L Leggett
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA -
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3
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Bermont A, Abu-Freha N, Cohen DL, Abu-Kaf H, Abu Juma A, Abu Galion F, Aminov R, Shirin H. Epidemiology and risk factors for angiodysplasias of the upper and lower gastrointestinal tract: A large population-based study. Dig Liver Dis 2025; 57:220-224. [PMID: 39155204 DOI: 10.1016/j.dld.2024.07.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 06/25/2024] [Accepted: 07/31/2024] [Indexed: 08/20/2024]
Abstract
BACKGROUND Gastrointestinal angiodysplasia (GIAD) is a rare diagnosis among the general population. We aimed to identify risk factors for GIADs and to determine the frequency rate in the general population. METHODS A population-based retrospective study was performed including patients diagnosed with upper (stomach/duodenum) or lower (small bowel/colon) GIADs based on diagnostic codes from a large health maintenance organization. Control groups were matched for age and gender. Additional data including demographics, comorbidities, malignancies, and medications were collected. RESULTS 991 upper GIADs and 3336 lower GIADs were included, compared to 7217 and 32,802 controls. The overall prevalence of GIAD was 0.092 %. 88 % of the upper and 85 % of the lower GIADs were diagnosed at ages ≥60, peaking at a prevalence of 0.37 % for ages 71-80. The most significant risk factors for GIADs included liver cirrhosis (OR 4.0 for lower GIAD and OR 7.0 for upper GIAD, p < 0.001), hypertension (OR 2.3 for lower GIAD and OR 2.8 for upper GIAD, p < 0.001) and aortic stenosis (OR 2.8 for lower GIAD and OR 2.0 for upper GIAD, p < 0.001). Other significant risk factors included ischemic heart disease, chronic renal failure, female gender, and chronic obstructive pulmonary disease. Interestingly, both upper and lower GIADs were found to be significantly less frequent in patients with malignancy. CONCLUSION Identification of the clinical conditions and demographic factors associated with GIAD may improve our understanding of the etiology and the optimal treatment modalities for this rare condition.
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Affiliation(s)
- Anton Bermont
- The Gonczarowski Family Institute of Gastroenterology and Liver Diseases, Shamir (Assaf Harofeh) Medical Center, School of Medicine Faculty of Medical and Health Sciences, Tel Aviv University, Zerifin, Israel.
| | - Naim Abu-Freha
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Daniel L Cohen
- The Gonczarowski Family Institute of Gastroenterology and Liver Diseases, Shamir (Assaf Harofeh) Medical Center, School of Medicine Faculty of Medical and Health Sciences, Tel Aviv University, Zerifin, Israel
| | - Heba Abu-Kaf
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Ali Abu Juma
- Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Fahmi Abu Galion
- Internal Medicine Department, Soroka University Medical Center, Beer-Sheva, Israel
| | - Refael Aminov
- Internal Medicine Department, Shamir (Assaf Harofeh) Medical Center, Israel
| | - Haim Shirin
- The Gonczarowski Family Institute of Gastroenterology and Liver Diseases, Shamir (Assaf Harofeh) Medical Center, School of Medicine Faculty of Medical and Health Sciences, Tel Aviv University, Zerifin, Israel
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Becq A, Sidhu R, Goltstein LCMJ, Dray X. Recent advances in the treatment of refractory gastrointestinal angiodysplasia. United European Gastroenterol J 2024; 12:1128-1135. [PMID: 39229890 PMCID: PMC11485408 DOI: 10.1002/ueg2.12648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 07/17/2024] [Indexed: 09/05/2024] Open
Abstract
Gastrointestinal angiodysplasia (GIA) is a common, acquired, vascular abnormality of the digestive tract, and a frequent cause of bleeding. Refractory GIA criteria usually include recurrent bleeding, transfusions and/or repeat endoscopy. Pharmacological and interventional treatments have been the subject of recent high-quality publications. This review provides an overview of the latest updates on non-endoscopic management of refractory GIA. Aortic valve replacement has shown its efficacy in Heyde syndrome and should be considered if indicated. Anti-angiogenic drugs, such as Octreotide and Thalidomide, are efficient treatments of refractory GIA-related bleeding. Somatostatin analogs should, based on efficacy and tolerance profile, be considered first. In the future, a better understanding of the physiopathology of GIA might help develop new-targeted therapies.
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Affiliation(s)
- Aymeric Becq
- Gastroenterology DepartmentParis‐Est Créteil UniversityHenri Mondor Hospital, AP HPCréteilFrance
| | - Reena Sidhu
- Division of Clinical MedicineSchool of Medicine and Population HealthUniversity of SheffieldSheffieldUK
- Academic Unit of Gastroenterology and HepatologySheffield Teaching HospitalsNHS Foundation TrustSheffieldUK
| | - Lia C. M. J. Goltstein
- Department of Gastroenterology and HepatologyRadboud University Medical CenterNijmegenThe Netherlands
| | - Xavier Dray
- Sorbonne UniversityCenter for Digestive EndoscopySaint Antoine Hospital, AP HPParisFrance
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Aldiabat M, Kilani Y, Alahmad M, Alhuneafat L, Aljabiri Y, Horoub A, Alabdallah K, Alrahamneh H, Manvar A. Inpatient Outcomes of Gastric Antral Vascular Ectasia in Those With Aortic Stenosis: A Retrospective Study of 85,000 Hospitalizations. J Clin Gastroenterol 2024; 58:769-775. [PMID: 37994146 DOI: 10.1097/mcg.0000000000001932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 08/31/2023] [Indexed: 11/24/2023]
Abstract
GOALS To investigate the outcomes of hospitalized patients with gastric antral vascular ectasia (GAVE) in the setting of aortic stenosis (AS). BACKGROUND Although AS is associated with gastrointestinal arteriovenous malformations, its association with GAVE, a rare cause of upper gastrointestinal bleeding, remains unknown. STUDY The National Inpatient Sample database from the years 2016 to 2019 was searched for patients admitted with a diagnosis of GAVE, with and without a history of AS. Univariate and multivariate logistic regression analysis was performed to determine the risk of mortality and in-hospital complications in the GAVE/AS group compared with the GAVE-only group. RESULTS Patients with AS had a 2-fold increase in the risk of GAVE [odds ratio (OR): 2.08, P < 0.001], with no statistically significant difference in inpatient mortality between the study groups (OR: 1.36, P = 0.268). Patients with GAVE-AS had a higher risk of hypovolemic shock (OR: 2.00, P = 0.001) and acute coronary syndromes (OR: 2.25, P < 0.001) with no difference in risk of cardiogenic shock ( P = 0.695), acute kidney injury ( P = 0.550), blood transfusion ( P = 0.270), sepsis ( P = 0.598), respiratory failure ( P = 0.200), or in-hospital cardiac arrest ( P = 0.638). The cost of care in patients with GAVE-AS was increased by a mean of $4729 ( P = 0.022), with no increase in length of stay ( P = 0.320) when compared with patients with GAVE-only. CONCLUSIONS Patients with AS have a 2-fold increase in the risk of development of GAVE. Patients with AS admitted for GAVE-related bleeding are at higher rates of hypovolemic shock, acute coronary syndrome, and higher resource utilization when compared with admitted patients with GAVE without AS.
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Affiliation(s)
- Mohammad Aldiabat
- Department of Medicine, Washington University in St. Louis, St. Louis
| | - Yassine Kilani
- Department of Medicine, Lincoln Medical Center/Weil Cornell Medicine
| | - Majd Alahmad
- Department of Medicine, University of Missouri-Columbia, Columbia, MO
| | - Laith Alhuneafat
- Department of Cardiovascular Medicine, University of Minnesota, Minneapolis, MN
| | - Yazan Aljabiri
- Department of Medicine, Washington University in St. Louis, St. Louis
| | - Ali Horoub
- Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx
| | - Khaled Alabdallah
- Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA
| | - Hebah Alrahamneh
- Department of Medicine, Mountainview Regional Medical Center, Las Cruces, NM
| | - Amar Manvar
- Division of Gastroenterology, Department of Medicine, NYU Langone Health, Mineola, NY
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Warkentin TE. A career in solving clinical-pathological conundrums: Heyde syndrome, anti-platelet factor 4 disorders, and microvascular limb ischemic necrosis. Int J Lab Hematol 2024; 46 Suppl 1:12-26. [PMID: 38432651 DOI: 10.1111/ijlh.14261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 02/14/2024] [Indexed: 03/05/2024]
Abstract
Hematology is a clinical specialty with strong roots in the laboratory; accordingly, the lab can help solve perplexing clinical problems. This review highlights clinical-pathological conundrums addressed during my 35-year hematology career at McMaster University. Heyde syndrome is the association between aortic stenosis and bleeding gastrointestinal (GI) angiodysplasia where the bleeding is usually cured by aortic valve replacement; the chance reading of a neonatal study showing reversible deficiency of high-molecular-weight (HMW) multimers of von Willebrand factor (vWF) following surgical correction of congenital heart disease provided the key insight that a subtle deficiency of HMW multimers of vWF explains Heyde syndrome. The unusual immunobiology of heparin-induced thrombocytopenia (HIT)-a highly prothrombotic, antibody-mediated, anti-platelet factor 4 (PF4) disorder featuring rapid appearance and then disappearance (seroreversion) of the pathological heparin-dependent platelet-activating antibodies-permitted identification of key clinical features that informed development of a scoring system (4Ts) to aid in HIT diagnosis. Atypical clinical presentations of HIT prompted identification of heparin-independent anti-PF4 antibodies, now recognized as the explanation for vaccine-induced immune thrombotic thrombocytopenia (VITT), as well as VITT-like disorders triggered by adenovirus infection. Another unusual feature of HIT is its strong association with limb ischemia, including limb necrosis secondary to deep-vein/microvascular thrombosis (venous limb gangrene). The remarkable observation that supratherapeutic warfarin anticoagulation predisposes to HIT- and cancer-associated venous limb gangrene provided insight into disturbed procoagulant/anticoagulant balance; these concepts are relevant to microvascular thrombosis in critical illness (symmetrical peripheral gangrene), including a pathophysiological role for proximate "shock liver" (impaired hepatic synthesis of natural anticoagulants).
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Affiliation(s)
- Theodore E Warkentin
- Department of Pathology and Molecular Medicine, and Department of Medicine, McMaster University, Hamilton, Ontario, Canada
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Sun D, Schaff HV, Lentz Carvalho J, Nishimura RA, Dearani JA, Ommen SR, Blackshear JL, Geske JB. Improvement in gastrointestinal bleeding after septal myectomy for hypertrophic cardiomyopathy. J Thorac Cardiovasc Surg 2024; 167:157-163. [PMID: 35577596 DOI: 10.1016/j.jtcvs.2022.04.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 03/10/2022] [Accepted: 04/03/2022] [Indexed: 11/29/2022]
Abstract
OBJECTIVE Patients with obstructive hypertrophic cardiomyopathy may have occult gastrointestinal bleeding. In this study, we analyzed outcomes of septal myectomy in patients who had a history of gastrointestinal bleeding preoperatively to understand patient characteristics and impact of septal reduction on recurrent gastrointestinal bleeding. METHODS We analyzed 73 adult patients who had a history of gastrointestinal bleeding before transaortic septal myectomy for obstructive hypertrophic cardiomyopathy and compared outcomes to 219 patients without gastrointestinal bleeding preoperatively. RESULTS Patients with preoperative history of gastrointestinal bleeding were older (median (IQR) age, 65 (59-69) years, P < .001) and were more likely to have systemic hypertension (70% vs 53%, P = .020) and coronary artery disease (25% vs 13%, P = .026). Preoperatively, patients with gastrointestinal bleeding had a larger left atrial volume index (median, 53 mL/m2; interquartile range, 42-67; P = .006) and greater right ventricular systolic pressure (median, 36 mm Hg; interquartile range, 32-49; mm Hg, P = .005) but no significant difference in severity of outflow tract obstruction (P = .368). There were no perioperative deaths. The estimated 5- and 10-year survivals were 96.6% and 81.8%, respectively. At a median of 3.4 (interquartile range, 1.9-9.1) years after septal myectomy, 11 patients (15%) had recurrence of gastrointestinal bleeding, which was attributed to angiodysplasia or unknown causes in 6 patients (8%). CONCLUSIONS Patients with a preoperative history of gastrointestinal bleeding have favorable short- and long-term outcomes after septal myectomy for obstructive hypertrophic cardiomyopathy. Remission of gastrointestinal bleeding was observed in 85% of patients postprocedure, and only 8% of the patients had recurrent gastrointestinal bleeding due to angiodysplasia or unknown causes.
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Affiliation(s)
- Daokun Sun
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minn
| | | | | | - Rick A Nishimura
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minn
| | - Joseph A Dearani
- Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minn
| | - Steve R Ommen
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minn
| | | | - Jeffrey B Geske
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minn
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8
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Goltstein LCMJ, Rooijakkers MJP, Hoeks M, Li WWL, van Wely MH, Rodwell L, van Royen N, Drenth JPH, van Geenen EJM. Effectiveness of aortic valve replacement in Heyde syndrome: a meta-analysis. Eur Heart J 2023; 44:3168-3177. [PMID: 37555393 PMCID: PMC10471563 DOI: 10.1093/eurheartj/ehad340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 03/22/2023] [Accepted: 04/13/2023] [Indexed: 08/10/2023] Open
Abstract
AIMS Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding. METHODS AND RESULTS A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002). CONCLUSION Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.
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Affiliation(s)
- Lia C M J Goltstein
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Geert Grooteplein Zuid 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Maxim J P Rooijakkers
- Department of Cardiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Marlijn Hoeks
- Department of Haematology, Radboud University Medical Center, Geert Grooteplein Zuid 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Wilson W L Li
- Department of Cardiothoracic Surgery, Radboud University Medical Center, Geert Grooteplein Zuid 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Marleen H van Wely
- Department of Cardiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Laura Rodwell
- Department of Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Section Biostatistics, Geert Grooteplein Zuid 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Niels van Royen
- Department of Cardiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Joost P H Drenth
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Geert Grooteplein Zuid 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
| | - Erwin-Jan M van Geenen
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Geert Grooteplein Zuid 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
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Ocran E, Chornenki NLJ, Bowman M, Sholzberg M, James P. Gastrointestinal bleeding in von Willebrand patients: special diagnostic and management considerations. Expert Rev Hematol 2023; 16:575-584. [PMID: 37278227 DOI: 10.1080/17474086.2023.2221846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 06/01/2023] [Indexed: 06/07/2023]
Abstract
INTRODUCTION Severe and recurrent gastrointestinal (GI) bleeding caused by angiodysplasia is a significant problem in patients with von Willebrand disease (VWD) and in those with acquired von Willebrand syndrome (AVWS). At present, angiodysplasia-related GI bleeding is often refractory to standard treatment including replacement therapy with von Willebrand factor (VWF) concentrates and continues to remain a major challenge and cause of significant morbidity in patients despite advances in diagnostics and therapeutics. AREAS COVERED This paper reviews the available literature on GI bleeding in VWD patients, examines the molecular mechanisms implicated in angiodysplasia-related GI bleeding, and summarizes existing strategies in the management of bleeding GI angiodysplasia in patients with VWF abnormalities. Suggestions are made for further research directions. EXPERT OPINION Bleeding from angiodysplasia poses a significant challenge for individuals with abnormal VWF. Diagnosis remains a challenge and may require multiple radiologic and endoscopic investigations. Additionally, there is a need for enhanced understanding at a molecular level to identify effective therapies. Future studies of VWF replacement therapies using newer formulations as well as other adjunctive treatments to prevent and treat bleeding will hopefully improve care.
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Affiliation(s)
- Edwin Ocran
- Department of Medicine, Queen's University, Kingston, Canada
| | | | | | - Michelle Sholzberg
- Division of Hematology-Oncology, St. Michael's Hospital, Li Ka Shing Knowledge Institute, University of Toronto, Toronto, Canada
| | - Paula James
- Department of Medicine, Queen's University, Kingston, Canada
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Pennazio M, Cortegoso Valdivia P, Triantafyllou K, Gralnek IM. Diagnosis and management of small-bowel bleeding. Best Pract Res Clin Gastroenterol 2023; 64-65:101844. [PMID: 37652647 DOI: 10.1016/j.bpg.2023.101844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 07/02/2023] [Indexed: 09/02/2023]
Abstract
Small-bowel (SB) bleeding is a challenging problem for the clinician, presenting many pitfalls in both diagnosis and subsequent treatment. Videocapsule endoscopy (VCE) and device-assisted enteroscopy (DAE) have revolutionized the approach to the patient with SB bleeding, allowing for the endoscopic diagnosis and management of what was previously only a surgical matter. The patients' assessment in SB bleeding is of foremost importance, as treatment success relies on a detailed evaluation of clinical history, suspicion for underlying lesions, and a careful selection and timing of diagnostic and therapeutic tools. This review will summarize current state-of-the-art evidence and practice points, to provide the clinician with a comprehensive guide towards the management of SB bleeding.
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Affiliation(s)
- Marco Pennazio
- University Division of Gastroenterology, City of Health and Science University Hospital, University of Turin, Turin, Italy.
| | - Pablo Cortegoso Valdivia
- Gastroenterology and Endoscopy Unit, University Hospital of Parma, University of Parma, Parma, Italy
| | - Konstantinos Triantafyllou
- Hepatogastroenterology Unit, Second Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece
| | - Ian M Gralnek
- Ellen and Pinchas Mamber Institute of Gastroenterology and Hepatology, Emek Medical Center, Afula, Israel; Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
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11
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Coisne A, Aghezzaf S, Butruille L, Woitrain E, Ninni S, Juthier F, Sudre A, Vincentelli A, Lamblin N, Lemesle G, Montaigne D, Bauters C. Incidence, source, and prognostic impact of major bleeding across the spectrum of aortic stenosis. Am Heart J 2023; 262:140-147. [PMID: 37100186 DOI: 10.1016/j.ahj.2023.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 03/30/2023] [Accepted: 04/07/2023] [Indexed: 05/30/2023]
Abstract
BACKGROUND Severe aortic stenosis (AS) has been associated with bleeding. However, there is a lack of prospective assessment of bleeding events and their clinical significance in a large population of outpatients with variable degree of AS severity. OBJECTIVES To assess the incidence, source, determinants, and prognostic impact of major bleeding in patients with variable degree of AS severity. METHODS Between May 2016 and December 2017, consecutive outpatients were included. Major bleeding was defined as type ≥3 bleed using the Bleeding Academic Research Consortium definition. Cumulative incidence was calculated with death as the competing event. Data was censored at time of aortic valve replacement. RESULTS Among 2,830 patients, 46 major bleeding events occurred (0.7%/year) during a median follow-up of 2.1 years (interquartile range: 1.4-2.7). Most frequent sites of bleeding were gastrointestinal (50%) and intracranial (30.4%). Major bleeding was significantly associated with all-cause mortality (hazard ratio: 5.93 (95% confidence interval 3.64-9.65); P < .001). AS severity was associated with major bleedings (P = .041). By multivariable analysis, severe AS was an independent determinant of major bleeding (hazard ratio vs mild AS: 3.59 [95% confidence interval 1.56-8.29]; P = .003). The increased risk of bleeding associated with severe AS was significantly exacerbated in patients using oral anticoagulation. CONCLUSION In AS patients, major bleeding is rare but a strong independent predictor of death. AS severity is a determinant of bleeding events. Severe AS and oral anticoagulation should be identified as an association at very high risk of major bleeding.
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Affiliation(s)
- Augustin Coisne
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France; Cardiovascular Research Foundation, New York, NY.
| | - Samy Aghezzaf
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Laura Butruille
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Eloise Woitrain
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Sandro Ninni
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Francis Juthier
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Arnaud Sudre
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - André Vincentelli
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Nicolas Lamblin
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Gilles Lemesle
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France; Heart and Lung Institute, University hospital of Lille, Lille, France; FACT (French Alliance for Cardiovascular Trials), Paris, France
| | - David Montaigne
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Christophe Bauters
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
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12
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Strategic Management of Bleeding Small Bowel Gastrointestinal Angiodysplasias (GIADs): A 12 Year Retrospective Review in a Veteran Population and Cost Comparison. Diagnostics (Basel) 2023; 13:diagnostics13030525. [PMID: 36766630 PMCID: PMC9914120 DOI: 10.3390/diagnostics13030525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/18/2023] [Accepted: 01/25/2023] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Gastrointestinal angiodysplasias (GIADs), also known as gastrointestinal angioectasias, are dilated, abnormally thin-walled blood vessels that occur in the mucosa and submucosa throughout the gastrointestinal tract. As a common cause of small bowel bleeding, GIADs have a significant impact on patient's morbidity and healthcare costs. Presently, somatostatin has been used widely to treat GIADs, but it is unclear if other therapies are as beneficial and cost-effective as somatostatin in managing GIADs. (2) Methods: A retrospective chart review was performed, which included subjects treated with Lanreotide, a somatostatin analog, and other therapies at the VA Loma Linda Healthcare System (VALLHCC) from January 2006 to December 2018. Patients who had symptomatic GIADs were detected by video capsule endoscopy (VCE), a device-assisted enteroscopy (DAE) or, in our case, push enteroscopy (PE) with an Endocuff. (3) Results: Three hundred twelve patients were diagnosed with GIADs. In this group of patients, 72 underwent ablation (endoscopic BICAP) with the addition of Lanreotide (SST), 63 underwent ablation therapy, eight were treated with SST only, 128 received iron replacement only, 25 received iron plus SST therapy, and 61 were observed with no therapy. Each group was followed via their hemoglobin (Hgb) level immediately thereafter, and Hgb levels were then obtained every 3 months for a 12-month period. After ablation therapy, 63 patients maintained stable Hgb levels over the course of the study, suggesting a significant therapeutic effect by controlling active bleeding. The 27 patients receiving ablation +SST therapy did not show improvements when compared to ablation only and the 128 patients who received iron therapy alone. (4) Conclusions: Importantly, 12 years of managing these patients has given us a cost- and time-sensitive strategy to maintain the patients' Hgb levels and avoid hospital admissions for acute bleeding. Iron treatment alone is effective compared to SST treatment in recovering from GIADs. Eliminating SST treatment from therapeutic intervention would save $89,100-445,550 per patient, depending on the number of doses for private care patients and $14,286-28,772 for VA patients, respectively. A suggested therapy would be to perform DAE on actively bleeding patients, ablate the lesions using a coagulation method, and place the patient on iron. If that fails, gastroenterologists should repeat VCE and perform either PE with Endocuff or balloon enteroscopy (all DAEs).
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13
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Yang X, Zhang J, Lai Y, Yan X, Guo X, Han J, Liu J, Wang J, Zhu H. Acquired von Willebrand Syndrome Secondary to Normally Functioning Mechanical Aortic Valve and High-Output Cardiac State. J Cardiovasc Dev Dis 2022; 9:jcdd9120454. [PMID: 36547451 PMCID: PMC9786303 DOI: 10.3390/jcdd9120454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 12/04/2022] [Accepted: 12/09/2022] [Indexed: 12/14/2022] Open
Abstract
Acquired von Willebrand syndrome (AVWS) is caused by an acquired deficiency of von Willebrand factor (VWF), a multimeric protein required for primary hemostasis. For patients with heart valve diseases, high gradient across the malfunctioning valves could cause elevated shear stress and damage the most effective large VWF, eventually resulting in AVWS. However, AVWS has not been reported in association with normally functioning mechanical valves. Herein, we reported a 74-year-old female who suffered from recurrent gastrointestinal bleeding with a history of mechanical aortic and mitral valve replacement. This patient's function/antigen ratio of VWF was decreased and gel electrophoresis revealed the loss of large VWF, which confirmed the diagnosis of AVWS. Echocardiogram showed that the function of the prostheses was normal. However, the gradient across aortic valve was increased due to a high cardiac state which is secondary to chronic anemia, resulting in the disruption of large VWF multimers and exacerbation of gastrointestinal (GI) bleeding. After managing the patient's anemia with transfusion, the gradient across the aortic valve had improved, with the resolution of GI bleeding. This is the first case report of AVWS that is associated with a normally functioning mechanical valve. AVWS should be considered one of the differential diagnoses if patients present with unexplained GI bleeding on the background of having prosthetic heart valves. The management of the underlying condition is essential.
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Affiliation(s)
- Xinglin Yang
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Jinghong Zhang
- Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
| | - Yamin Lai
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Xuemin Yan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Xiaoxiao Guo
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Jianhua Han
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Jihai Liu
- Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Jiangshan Wang
- Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
- Correspondence:
| | - Huadong Zhu
- Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
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14
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Kozlov S, Okhota S, Avtaeva Y, Melnikov I, Matroze E, Gabbasov Z. Von Willebrand factor in diagnostics and treatment of cardiovascular disease: Recent advances and prospects. Front Cardiovasc Med 2022; 9:1038030. [PMID: 36531725 PMCID: PMC9755348 DOI: 10.3389/fcvm.2022.1038030] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 11/21/2022] [Indexed: 10/10/2023] Open
Abstract
Von Willebrand factor (VWF) is a large multimeric glycoprotein involved in hemostasis. It is essential for platelet adhesion to the subendothelium of the damaged endothelial layer at high shear rates. Such shear rates occur in small-diameter arteries, especially at stenotic sites. Moreover, VWF carries coagulation factor VIII and protects it from proteolysis in the bloodstream. Deficiency or dysfunction of VWF predisposes to bleeding. In contrast, an increase in the concentration of high molecular weight multimers (HMWM) of VWF is closely associated with arterial thrombotic events. Severe aortic stenosis (AS) or hypertrophic obstructive cardiomyopathy (HOCM) can deplete HMWM of VWF and lead to cryptogenic, gastrointestinal, subcutaneous, and mucosal bleeding. Considering that VWF facilitates primary hemostasis and a local inflammatory response at high shear rates, its dysfunction may contribute to the development of coronary artery disease (CAD) and its complications. However, current diagnostic methods do not allow for an in-depth analysis of this contribution. The development of novel diagnostic techniques, primarily microfluidic, is underway. Such methods can provide physiologically relevant assessments of VWF function at high shear rates; however, they have not been introduced into clinical practice. The development and use of agents targeting VWF interaction with the vessel wall and/or platelets may be reasonable in prevention of CAD and its complications, given the prominent role of VWF in arterial thrombosis.
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Affiliation(s)
- Sergey Kozlov
- Department of Problems of Atherosclerosis, National Medical Research Centre of Cardiology Named After Academician E.I. Chazov of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Sergey Okhota
- Department of Problems of Atherosclerosis, National Medical Research Centre of Cardiology Named After Academician E.I. Chazov of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Yuliya Avtaeva
- Laboratory of Cell Hemostasis, National Medical Research Centre of Cardiology Named After Academician E.I. Chazov of the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Ivan Melnikov
- Laboratory of Cell Hemostasis, National Medical Research Centre of Cardiology Named After Academician E.I. Chazov of the Ministry of Health of the Russian Federation, Moscow, Russia
- Laboratory of Gas Exchange, Biomechanics and Barophysiology, State Scientific Center of the Russian Federation—The Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia
| | - Evgeny Matroze
- Laboratory of Cell Hemostasis, National Medical Research Centre of Cardiology Named After Academician E.I. Chazov of the Ministry of Health of the Russian Federation, Moscow, Russia
- Department of Innovative Pharmacy, Medical Devices and Biotechnology, Moscow Institute of Physics and Technology, Moscow, Russia
| | - Zufar Gabbasov
- Laboratory of Cell Hemostasis, National Medical Research Centre of Cardiology Named After Academician E.I. Chazov of the Ministry of Health of the Russian Federation, Moscow, Russia
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15
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Hung HJ, Chung CS, Tai CM, Chang CW, Tseng CM, Huang GS, Lin MC, Huang TY. Clinical characteristics and risk factors for rebleeding in uremic patients with obscure gastrointestinal bleeding undergoing deep enteroscopy: A multi-center retrospective study in Taiwan. PLoS One 2022; 17:e0277434. [PMID: 36449459 PMCID: PMC9710796 DOI: 10.1371/journal.pone.0277434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 10/26/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND/PURPOSE Recurrent obscure gastrointestinal bleeding (OGIB) in patients with chronic kidney disease is a challenge often faced by physicians, given the need for repeated hospitalizations, multiple extensive examinations, limited treatment options, and high medical costs. The purpose of this study was to identify the clinical characteristics of uremic patients undergoing deep enteroscopy for OGIB and analyze the risk factors for rebleeding in these patients after undergoing single-balloon enteroscopy (SBE). METHODS Out of 765 patients with OGIB who underwent 1004 procedures of SBE in four teaching hospitals, 78 uremic patients with OGIB were enrolled. Clinical characteristics and endoscopic findings were collected, and multiple variables were analyzed to determine the risk of rebleeding after SBE. RESULTS The diagnostic yield was 75.6%, and the rebleeding rate was 29.5% in the enrolled uremic patients. The most common etiology was angiodysplasia (74.6%) and the most common site was the jejunum (50.8%). The endoscopic intervention rate was 62.8% and most patients were treated with argon plasma coagulation (75.6%). Among the eight patients with valvular heart disease (VHD), four (50%) had severe aortic stenosis, and the remaining had non-aortic stenosis-VHD. VHD (p < 0.05) and angiodysplasia (p < 0.05) were both associated with a higher rebleeding rate. CONCLUSION VHD may be an independent risk factor associated with rebleeding after SBE in uremic patients with OGIB. Moreover, uremic patients with angiodysplasia-related bleeding appear to have a higher rebleeding rate than those with alternative causes of bleeding.
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Affiliation(s)
- Hsuan-Jen Hung
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chen-Shuan Chung
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
- Taiwan Association for the Study of Small Intestinal Diseases, Taoyuan, Taiwan
| | - Chi-Ming Tai
- Taiwan Association for the Study of Small Intestinal Diseases, Taoyuan, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan
| | - Chen-Wang Chang
- Taiwan Association for the Study of Small Intestinal Diseases, Taoyuan, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan
| | - Chao-Ming Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan
| | - Go-Shine Huang
- Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Meng-Chiung Lin
- Division of Gastroenterology, Department of Internal Medicine, Taichiung Armed Forces General Hospital, Taichiung, Taiwan
| | - Tien-Yu Huang
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Taiwan Association for the Study of Small Intestinal Diseases, Taoyuan, Taiwan
- * E-mail:
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16
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Dweik A, Al-Jabory O, Rasheed W, Anees MA, Dweik N. An Important Association With Lower GI Bleed: A Case of Heyde Syndrome. Cureus 2022; 14:e26232. [PMID: 35898365 PMCID: PMC9308369 DOI: 10.7759/cureus.26232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/23/2022] [Indexed: 11/11/2022] Open
Abstract
The association between aortic stenosis and angiodysplastic gastrointestinal bleed is known as Heyde syndrome. It was first described in 1958 and has since received further medical attention. We present a case of an 86-year-old lady with a history of severe aortic stenosis that was admitted with gastrointestinal bleeding secondary to colonic angiodysplasia. A review of the literature showed mixed opinions with respect to the idea of causation versus coincidence; both theories are valid. However, studies that supported causation had a bigger study population and overall seem to be more plausible.
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17
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Circulating Monocyte Subsets and Transcatheter Aortic Valve Replacement. Int J Mol Sci 2022; 23:ijms23105303. [PMID: 35628113 PMCID: PMC9141814 DOI: 10.3390/ijms23105303] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/02/2022] [Accepted: 05/07/2022] [Indexed: 11/17/2022] Open
Abstract
Transcatheter aortic valve replacement (TAVR), as an alternative to open heart surgery, has revolutionized the treatment of severe aortic valve stenosis (AVS), the most common valvular disorder in the elderly. AVS is now considered a form of atherosclerosis and, like the latter, partly of inflammatory origin. Patients with high-grade AVS have a highly disturbed blood flow associated with high levels of shear stress. The immediate reopening of the valve during TAVR leads to a sudden restoration of a normal blood flow hemodynamic. Despite its good prognosis for patients, TAVR remains associated with bleeding or thrombotic postprocedural complications, involving mechanisms that are still poorly understood. Many studies report the close link between blood coagulation and inflammation, termed thromboinflammation, including monocytes as a major actor. The TAVR procedure represents a unique opportunity to study the influence of shear stress on human monocytes, key mediators of inflammation and hemostasis processes. The purpose of this study was to conduct a review of the literature to provide a comprehensive overview of the impact of TAVR on monocyte phenotype and subset repartition and the association of these parameters with the clinical outcomes of patients with severe AVS who underwent TAVR.
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18
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Minamimoto Y, Hibi K, Kirigaya J, Takahashi H, Matsushita K, Iwahashi N, Matsuzawa Y, Maejima N, Kosuge M, Ebina T, Sugano T, Ishikawa T, Tamura K, Kimura K. Feasibility and safety of transradial balloon aortic valvuloplasty in patients with severe aortic stenosis. Cardiovasc Interv Ther 2022; 37:558-565. [PMID: 34981414 DOI: 10.1007/s12928-021-00825-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 11/08/2021] [Indexed: 11/26/2022]
Abstract
Balloon aortic valvuloplasty (BAV) was developed as a technique to treat aortic stenosis (AS) and is associated with significant improvements in aortic valve area and trans-aortic valve gradient in the early and immediate periods after the procedure. BAV is commonly performed using a trans-femoral retrograde approach; however, trans-femoral access is associated with frequent access-site bleeding. Among 146 patients with symptomatic severe AS who were treated with BAV in our institution, 123 patients received BAV treatment via a trans-radial approach using a 7-Fr Glidesheath. The balloon size was 16-20 mm for all patients. Echocardiograms were obtained before and after BAV. Patients who received BAV alone (n = 119) were followed up for 3 months, and major adverse events (stroke, re-hospitalization for heart failure, and death) and procedural complications were recorded. At post-procedural echocardiography, the mean trans-valvular gradient (49.7 ± 21.5-42.5 ± 17.6 mmHg; p < 0.0001) was reduced significantly. All patients in this study did not die or require valve surgery within the first 7 days after BAV. Successful BAV was obtained in 45.6% of the patients. No patients had severe aortic insufficiency or BAV access-site bleeding. Three patients died suddenly and 4 patients were readmitted for heart failure. Trans-radial BAV is safe and may be useful as a bridging therapy for trans-catheter aortic valve replacement or surgical aortic valve replacement.
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Affiliation(s)
- Yugo Minamimoto
- Division of Cardiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kiyoshi Hibi
- Division of Cardiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan.
| | - Jin Kirigaya
- Division of Cardiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan
| | - Hironori Takahashi
- Division of Cardiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan
| | - Kensuke Matsushita
- Division of Cardiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan
| | - Noriaki Iwahashi
- Division of Cardiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan
| | - Yasushi Matsuzawa
- Division of Cardiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan
| | - Nobuhiko Maejima
- Division of Cardiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan
| | - Masami Kosuge
- Division of Cardiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan
| | - Toshiaki Ebina
- Division of Cardiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan
| | - Teruyasu Sugano
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Toshiyuki Ishikawa
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kouichi Tamura
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kazuo Kimura
- Division of Cardiology, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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19
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Al-Radaideh O, Farouji I, Abed H, Shaaban H. Recurrent gastrointestinal bleeding in a patient with Heyde syndrome with elevated factor VIII levels: A case report. Int J Crit Illn Inj Sci 2021; 11:253-256. [PMID: 35070916 PMCID: PMC8725811 DOI: 10.4103/ijciis.ijciis_151_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Revised: 03/11/2021] [Accepted: 03/26/2021] [Indexed: 11/23/2022] Open
Abstract
Heyde syndrome is the association between gastrointestinal (GI) bleeding from intestinal angiodysplasia (IA) and aortic stenosis (AS). Although the course of disease progression that links AS and GI bleeding has not been determined, overlaps among AS, intestinal dysplasia, and acquired von Willebrand's syndrome is thought to result in GI bleeding. Proper repair of the aortic valve can result in significant improvement of GI bleeding and its recurrence. Herein, we are reporting this rare case, in which a patient with moderate AS on echocardiogram presents with recurrent GI bleeding from multiple IA in the setting of elevated factor VIII levels, to propose a theory that angiodysplasia could potentially develop due to intermittent, recurrent low-grade obstruction of submucosal veins at the level of the muscularis propria secondary to venous thrombosis related to elevated factor VIII levels.
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Affiliation(s)
- Omar Al-Radaideh
- Department of Medical Education, Saint Michael's Medical Center, New York Medical College, Newark, NJ, USA
| | - Iyad Farouji
- Department of Medical Education, Saint Michael's Medical Center, New York Medical College, Newark, NJ, USA
| | - Hossam Abed
- Department of Medical Education, Saint Michael's Medical Center, New York Medical College, Newark, NJ, USA
| | - Hamid Shaaban
- Department of Medical Education, Saint Michael's Medical Center, New York Medical College, Newark, NJ, USA.,Department of Hematology/Oncology, Saint Michael's Medical Center, New York Medical College, Newark, NJ, USA
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20
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Lourdusamy D, Mupparaju VK, Sharif NF, Ibebuogu UN. Aortic stenosis and Heyde’s syndrome: A comprehensive review. World J Clin Cases 2021; 9:7319-7329. [PMID: 34616798 PMCID: PMC8464459 DOI: 10.12998/wjcc.v9.i25.7319] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 07/07/2021] [Accepted: 07/26/2021] [Indexed: 02/06/2023] Open
Abstract
Heyde’s syndrome is an under reported systemic disease of gastrointestinal and cardiac manifestation in older adults. It is characterized by a triad of aortic stenosis, angiodysplasia with bleeding and acquired von Willebrand syndrome. It is characterized by proteolysis of high molecular weight multimers of von Willebrand Factor and loss of platelet mediated homeostasis. Heyde’s syndrome is a treatable condition in most cases, especially in the current era of evolution in interventional cardiology and gastroenterology. There are currently no established guidelines in the management of this condition due to paucity of high quality studies, which warrant future trials. High index of suspicion and increasing the awareness of the syndrome among the general practitioners and sub-specialists will improve the diagnostic potential of Heyde’s syndrome. Future studies may change the management aspect of Heyde's syndrome and pave a path for drawing specific guidelines and algorithms. The aim of our review article is to summarize the basic pathophysiology, diagnostics and management of Heyde’s syndrome with a special attention to Transcatheter aortic valve replacement.
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Affiliation(s)
| | | | - Navila Fahmida Sharif
- Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38103, United States
| | - Uzoma N Ibebuogu
- Cardiovascular Diseases, University of Tennessee Health Science Center, Memphis, TN 38163, United States
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21
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Abstract
Acquired von Willebrand syndrome can occur in the setting of myeloproliferative neoplasms; plasma cell dyscrasias and other lymphoproliferative disorders; autoimmune conditions; and causes of increased shear forces, such as aortic stenosis or other structural heart disease and mechanical circulatory support. The depletion of von Willebrand factor, especially high-molecular-weight multimers, can lead to mucocutaneous bleeding and the formation of arteriovenous malformations, particularly in the gastrointestinal tract. Management focuses on correction of the underlying cause when possible, but may include intravenous immunoglobulins, von Willebrand factor concentrate, rituximab, or antiangiogenic therapy depending on the clinical context.
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Affiliation(s)
- Arielle L Langer
- Division of Hematology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
| | - Nathan T Connell
- Division of Hematology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
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22
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Johnson AM, Chovwen PE, Akpan EJ, Patel A. Aortic Valve Stenosis, a Precipitating Factor of Recurrent Bleed in Colonic Angiodysplasia: A Literature Review. Cureus 2021; 13:e15903. [PMID: 34322347 PMCID: PMC8310456 DOI: 10.7759/cureus.15903] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/24/2021] [Indexed: 12/16/2022] Open
Abstract
Angiodysplasia (also known as angioectasia) is a lesion characterized by abnormal, dilated small blood vessels in the mucosa and submucosal layers of the GI tract. With the estimated low incidence of active GI bleeding from these lesions, angiodysplasia can be challenging to diagnose. The presence of aortic stenosis has increased the recognition rate of angiodysplasia, especially in the elderly. Despite the associations between aortic stenosis and angiodysplasia (Heyde's syndrome) revealed in several studies, the etiology of Heyde syndrome is still debatable, which has led to the proposition of several hypotheses that are reviewed in this article. This activity will help review the meaning of Heyde's syndrome, epidemiology, proposed pathophysiology, diagnosis, and management by surveying articles published between 1955 and 2021 on PubMed. We used search terms such as "colonic angiodysplasia," "arteriovenous malformation," "Heyde syndrome," "refractory gastrointestinal bleed," "aortic valve stenosis," and "acquired von Willebrand disease." Findings revealed an association between aortic stenosis and lower gastrointestinal (GI) bleed.
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Affiliation(s)
| | | | - Ezekiel J Akpan
- Medicine, All Saints University College of Medicine, Kingstown, VCT
| | - Anna Patel
- Gastroenterology and Hepatology, Community First Medical Center, Chicago, USA
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23
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Thakar S, Gabarin N, Gupta A, Radford M, Warkentin TE, Arnold DM. Anemia-Induced Bleeding in Patients with Platelet Disorders. Transfus Med Rev 2021; 35:22-28. [PMID: 34332828 DOI: 10.1016/j.tmrv.2021.06.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 06/06/2021] [Accepted: 06/07/2021] [Indexed: 11/26/2022]
Abstract
Anemia is not only a consequence of bleeding, but also a modifiable risk factor for bleeding in patients with thrombocytopenia or platelet function defects. In this review we outline the mechanism of anemia-induced bleeding in patients with platelet disorders, which involves a disturbance in normal red blood cell (RBC) rheology and reduced platelet margination to the endothelial surface due to a decrease in RBC mass, leading to impaired primary hemostasis and bleeding. Biologically, anemia reduces the mass of RBCs in the central column of flowing blood through a vessel resulting in fewer platelets coming into contact with the endothelial surface at the periphery of the flowing blood column. Thus, anemia results in impaired primary hemostasis. Von Willebrand factor (vWF) is another component of primary hemostasis and vWF deficiency, especially a deficiency of the highest vWF multimers, can also manifest with bleeding when concomitant anemia occurs. Clinically, patients at greatest risk for anemia-induced bleeding include patients with hematological malignancies in whom anemia and thrombocytopenia occur as a result of the underlying disease or the myelotoxic effects of treatment; patients with renal insufficiency with uremic thrombocytopathy and hypoproliferative anemia; and patients with inherited or acquired bleeding disorders affecting primary hemostasis (eg, Bernard-Soulier syndrome, von Willebrand disease) with chronic blood loss and iron deficiency anemia. Underlying abnormalities of any components of primary hemostasis plus concomitant anemia may result in major bleeding disorders; therefore, correction of remediable abnormalities-most notably, correction of the anemia- would be expected to have important clinical benefit. In this review we discuss how the correction of the anemia may lead to improvement of bleeding outcomes in patients with a primary hemostatic defect, supported by evidence from animal models, clinical trials and clinical experience.
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Affiliation(s)
- Swarni Thakar
- McMaster Center for Transfusion Research, McMaster University, Hamilton, Ontario, Canada
| | - Nadia Gabarin
- Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Akash Gupta
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Michael Radford
- Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Theodore E Warkentin
- McMaster Center for Transfusion Research, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Donald M Arnold
- McMaster Center for Transfusion Research, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
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24
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Wang S, Griffith BP, Wu ZJ. Device-Induced Hemostatic Disorders in Mechanically Assisted Circulation. Clin Appl Thromb Hemost 2021; 27:1076029620982374. [PMID: 33571008 PMCID: PMC7883139 DOI: 10.1177/1076029620982374] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Mechanically assisted circulation (MAC) sustains the blood circulation in the body of a patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) or on ventricular assistance with a ventricular assist device (VAD) or on extracorporeal membrane oxygenation (ECMO) with a pump-oxygenator system. While MAC provides short-term (days to weeks) support and long-term (months to years) for the heart and/or lungs, the blood is inevitably exposed to non-physiological shear stress (NPSS) due to mechanical pumping action and in contact with artificial surfaces. NPSS is well known to cause blood damage and functional alterations of blood cells. In this review, we discussed shear-induced platelet adhesion, platelet aggregation, platelet receptor shedding, and platelet apoptosis, shear-induced acquired von Willebrand syndrome (AVWS), shear-induced hemolysis and microparticle formation during MAC. These alterations are associated with perioperative bleeding and thrombotic events, morbidity and mortality, and quality of life in MCS patients. Understanding the mechanism of shear-induce hemostatic disorders will help us develop low-shear-stress devices and select more effective treatments for better clinical outcomes.
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Affiliation(s)
- Shigang Wang
- Department of Surgery, 12264University of Maryland School of Medicine, Baltimore, MD, USA
| | - Bartley P Griffith
- Department of Surgery, 12264University of Maryland School of Medicine, Baltimore, MD, USA
| | - Zhongjun J Wu
- Department of Surgery, 12264University of Maryland School of Medicine, Baltimore, MD, USA.,Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD, USA
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25
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Belov DV, Garbuzenko DV, Lukin OP, Anufrieva SS. Heyde’s syndrome as a rare cause of gastrointestinal bleeding in aortic stenosis patients. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2021. [DOI: 10.15829/1728-8800-2021-2503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- D. V. Belov
- Federal Center for Cardiovascular Surgery; South Ural State Medical University
| | | | - O. P. Lukin
- Federal Center for Cardiovascular Surgery; South Ural State Medical University
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26
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Abstract
Heyde syndrome is a triad of bleeding colonic angiodysplasia, aortic stenosis, and acquired coagulopathy. It is most commonly seen in the elderly between 60-80 years of age. We present a case of Heyde syndrome presenting with severe anemia secondary to bleeding angiodysplasia or arteriovenous malformations (AVM) in the lower gastrointestinal (GI) tract.
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Affiliation(s)
- Samridhi Sinha
- Internal Medicine, The Brooklyn Hospital Center/Mount Sinai Heart, Brooklyn, USA
| | - Daniel Castro
- Hemotolgy and Oncology, The Brooklyn Hospital Center/Mount Sinai Heart, Brooklyn, USA.,Internal Medicine, The Brooklyn Hospital Center, Brooklyn, USA
| | - Shams Shakil
- Hematology and Oncology, The Brooklyn Hospital Center/Mount Sinai Heart, Brooklyn, USA
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27
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Dall'Ara G, Grotti S, Conficoni E, Poletti G, Valpiani D, Carletti R, Compagnone M, Tarantino F, Galvani M. Early Resolution of Heyde's Syndrome following Transcatheter Aortic Valve Replacement. Semin Thromb Hemost 2020; 47:102-104. [PMID: 33368116 DOI: 10.1055/s-0040-1718871] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Affiliation(s)
| | - Simone Grotti
- Cardiology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy
| | | | - Giovanni Poletti
- Clinical Pathology Unit, AUSL Romagna, Pievesestina, Cesena, Italy
| | - Daniela Valpiani
- Department of Gastroenterology and Digestive Endoscopy, Morgagni-Pierantoni Hospital, Forlì, Italy
| | | | | | | | - Marcello Galvani
- Cardiology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy.,Cardiovascular Research Unit, Myriam Zito Sacco Heart Foundation, Forlì, Italy
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28
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Shear Stress-Induced Activation of von Willebrand Factor and Cardiovascular Pathology. Int J Mol Sci 2020; 21:ijms21207804. [PMID: 33096906 PMCID: PMC7589699 DOI: 10.3390/ijms21207804] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 10/19/2020] [Accepted: 10/20/2020] [Indexed: 12/11/2022] Open
Abstract
The von Willebrand factor (vWF) is a plasma protein that mediates platelet adhesion and leukocyte recruitment to vascular injury sites and carries coagulation factor VIII, a building block of the intrinsic pathway of coagulation. The presence of ultra-large multimers of vWF in the bloodstream is associated with spontaneous thrombosis, whereas its deficiency leads to bleeding. In cardiovascular pathology, the progression of the heart valve disease results in vWF deficiency and cryptogenic gastrointestinal bleeding. The association between higher plasma levels of vWF and thrombotic complications of coronary artery disease was described. Of note, it is not the plasma levels that are crucial for vWF hemostatic activity, but vWF activation, triggered by a rise in shear rates. vWF becomes highly reactive with platelets upon unfolding into a stretched conformation, at shear rates above the critical value (more than 5000 s−1), which might occur at sites of arterial stenosis and injury. The activation of vWF and its counterbalance by ADAMTS-13, the vWF-cleaving protease, might contribute to complications of cardiovascular diseases. In this review, we discuss vWF involvement in complications of cardiovascular diseases and possible diagnostic and treatment approaches.
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29
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Casonato A, Galletta E, Cella G, Barbon G, Daidone V. Acquired von Willebrand Syndrome Hiding Inherited von Willebrand Disease Can Explain Severe Bleeding in Patients With Aortic Stenosis. Arterioscler Thromb Vasc Biol 2020; 40:2187-2194. [PMID: 32640909 DOI: 10.1161/atvbaha.120.314656] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE Aortic stenosis may be complicated by an acquired von Willebrand syndrome that rarely causes significant bleeding, raising the question of why it does so in a few cases. To seek an explanation, we studied 5 severe bleeder aortic stenosis patients in a cohort of 49 patients, using the flowchart for inherited von Willebrand disease. Approach and Results: All 5 patients were lacking in large and intermediate VWF (von Willebrand factor) multimers, 3 had reduced plasma and platelet VWF levels, and none showed PFA100 closure. Two patients (those with most multimers missing) also had a short VWF half-life. Genetic analyses on the 3 patients with reduced platelet VWF levels revealed that one carried both the c.1164C>G and the c.7880G>A mutations, and another carried the c.3390C>T mutation, while the third had one of the 2 VWF alleles relatively less expressed than the other (25% versus 75%). No genetic alterations emerged in the other 2 patients. Successful replacement of the stenotic aortic valve, performed in the 2 patients with VWF mutations, did not correct their abnormal VWF multimer picture-unlike what happened in the aortic stenosis patients without bleeding symptoms. CONCLUSIONS Our findings suggest that acquired von Willebrand syndrome can develop in patients with hitherto-undiagnosed inherited von Willebrand disease. Since von Willebrand disease is the most common bleeding disorder, this possibility should be considered in aortic stenosis patients-especially those with a more severe bleeding history and more disrupted VWF laboratory patterns-because they risk hemorrhage during aortic valve replacement.
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Affiliation(s)
- Alessandra Casonato
- From the Department of Medicine, First Chair of Internal Medicine (A.C., E.G., G.B., V.D.), University of Padua Medical School, Italy
| | - Eva Galletta
- From the Department of Medicine, First Chair of Internal Medicine (A.C., E.G., G.B., V.D.), University of Padua Medical School, Italy
| | - Giuseppe Cella
- Department of Cardiac, Thoracic and Vascular Sciences (G.C.), University of Padua Medical School, Italy
| | - Giovanni Barbon
- From the Department of Medicine, First Chair of Internal Medicine (A.C., E.G., G.B., V.D.), University of Padua Medical School, Italy
| | - Viviana Daidone
- From the Department of Medicine, First Chair of Internal Medicine (A.C., E.G., G.B., V.D.), University of Padua Medical School, Italy
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30
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Otani T, Hatakeyama K, Yamashita K, Hayata Y, Hayakawa M, Matsumoto M, Taniguchi S, Ohbayashi C. A histological description of intestinal 'angiodysplasia' in an autopsy case of Heyde's syndrome. Pathol Int 2020; 69:727-729. [PMID: 31872535 DOI: 10.1111/pin.12874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Tomoyuki Otani
- Department of Diagnostic Pathology, Nara Medical University, Nara, Japan.,Department of Pathology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Kinta Hatakeyama
- Department of Diagnostic Pathology, Nara Medical University, Nara, Japan
| | - Keigo Yamashita
- Department of Thoracic and Cardiovascular Surgery, Nara Medical University, Nara, Japan
| | - Yoshihiro Hayata
- Department of Thoracic and Cardiovascular Surgery, Nara Medical University, Nara, Japan
| | - Masaki Hayakawa
- Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan
| | - Masanori Matsumoto
- Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan
| | - Shigeki Taniguchi
- Department of Thoracic and Cardiovascular Surgery, Nara Medical University, Nara, Japan
| | - Chiho Ohbayashi
- Department of Diagnostic Pathology, Nara Medical University, Nara, Japan
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31
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Van Belle E, Vincent F, Rauch A, Casari C, Jeanpierre E, Loobuyck V, Rosa M, Delhaye C, Spillemaeker H, Paris C, Debry N, Verdier B, Vincentelli A, Dupont A, Lenting PJ, Susen S. von Willebrand Factor and Management of Heart Valve Disease: JACC Review Topic of the Week. J Am Coll Cardiol 2020; 73:1078-1088. [PMID: 30846101 DOI: 10.1016/j.jacc.2018.12.045] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 12/30/2018] [Indexed: 10/27/2022]
Abstract
For decades, numerous observations have shown an intimate relationship between von Willebrand factor (VWF) multimer profile and heart valve diseases (HVD). The current knowledge of the unique biophysical properties of VWF helps us to understand the longstanding observations concerning the bleeding complications in patients with severe HVD. Not only does the analysis of the VWF multimer profile provide an excellent evaluation of HVD severity, it is also a strong predictor of clinical events. Also of importance, VWF responds within minutes to any significant change in hemodynamic valve status, making it an accurate marker of the quality of surgical and transcatheter therapeutic interventions. The authors provide in this review a practical, comprehensive, and evidence-based framework of the concept of VWF as a biomarker in HVD, advocating for its implementation into the clinical decision-making process besides usual clinical and imaging evaluation. They also delineate critical knowledge gaps and research priorities to definitely validate this concept.
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Affiliation(s)
- Eric Van Belle
- CHU Lille, Université de Lille, Inserm U1011 - EGID, Institut Pasteur de Lille, Lille, France; CHU Lille, Institut Coeur Poumon, Cardiology, Lille, France
| | - Flavien Vincent
- CHU Lille, Université de Lille, Inserm U1011 - EGID, Institut Pasteur de Lille, Lille, France; CHU Lille, Institut Coeur Poumon, Cardiology, Lille, France
| | - Antoine Rauch
- CHU Lille, Université de Lille, Inserm U1011 - EGID, Institut Pasteur de Lille, Lille, France; CHU Lille, Hematology and Transfusion, Lille, France
| | - Caterina Casari
- Inserm, UMR_S 1176, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Emmanuelle Jeanpierre
- CHU Lille, Université de Lille, Inserm U1011 - EGID, Institut Pasteur de Lille, Lille, France; CHU Lille, Hematology and Transfusion, Lille, France
| | - Valentin Loobuyck
- CHU Lille, Université de Lille, Inserm U1011 - EGID, Institut Pasteur de Lille, Lille, France; CHU Lille, Institut Coeur Poumon, Cardiac Surgery, Lille, France
| | - Mickael Rosa
- CHU Lille, Université de Lille, Inserm U1011 - EGID, Institut Pasteur de Lille, Lille, France
| | - Cedric Delhaye
- CHU Lille, Institut Coeur Poumon, Cardiology, Lille, France
| | | | - Camille Paris
- CHU Lille, Université de Lille, Inserm U1011 - EGID, Institut Pasteur de Lille, Lille, France; CHU Lille, Hematology and Transfusion, Lille, France
| | - Nicolas Debry
- CHU Lille, Institut Coeur Poumon, Cardiology, Lille, France
| | - Basile Verdier
- CHU Lille, Institut Coeur Poumon, Cardiology, Lille, France
| | - André Vincentelli
- CHU Lille, Université de Lille, Inserm U1011 - EGID, Institut Pasteur de Lille, Lille, France; CHU Lille, Institut Coeur Poumon, Cardiac Surgery, Lille, France
| | - Annabelle Dupont
- CHU Lille, Université de Lille, Inserm U1011 - EGID, Institut Pasteur de Lille, Lille, France
| | - Peter J Lenting
- Inserm, UMR_S 1176, Université Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Sophie Susen
- CHU Lille, Université de Lille, Inserm U1011 - EGID, Institut Pasteur de Lille, Lille, France; CHU Lille, Hematology and Transfusion, Lille, France.
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32
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Leebeek FWG, Muslem R. Bleeding in critical care associated with left ventricular assist devices: pathophysiology, symptoms, and management. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2019; 2019:88-96. [PMID: 31808855 PMCID: PMC6913502 DOI: 10.1182/hematology.2019000067] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
Chronic heart failure (HF) is a growing health problem, and it is associated with high morbidity and mortality. Left ventricular assist devices (LVADs) are nowadays an important treatment option for patients with end-stage HF not only as a bridging tool to heart transplantation but also, as a permanent therapy for end-stage HF (destination therapy). The use of LVAD is associated with a high risk for bleeding complications and thromboembolic events, including pump thrombosis and ischemic stroke. Bleeding is the most frequent complication, occurring in 30% to 60% of patients, both early and late after LVAD implantation. Although the design of LVADs has improved over time, bleeding complications are still the most common complication and occur very frequently. The introduction of an LVAD results in an altered hemostatic balance as a consequence of blood-pump interactions, changes in hemodynamics, acquired coagulation abnormalities, and the strict need for long-term anticoagulant treatment with oral anticoagulants and antiplatelet therapy. LVAD patients may experience an acquired coagulopathy, including platelet dysfunction and impaired von Willebrand factor activity, resulting in acquired von Willebrand syndrome. In this educational manuscript, the epidemiology, etiology, and pathophysiology of bleeding in patients with LVAD will be discussed. Because hematologist are frequently consulted in cases of bleeding problems in these individuals in a critical care setting, the observed type of bleeding complications and management strategies to treat bleeding are also reviewed.
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Affiliation(s)
| | - R Muslem
- Cardio-Thoracic Surgery, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
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33
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Mehran R, Sorrentino S, Claessen BE. Paravalvular Leak: An Interesting Interplay of Acquired vWF-Disease and Late Bleeding After TAVR. J Am Coll Cardiol 2019; 72:2149-2151. [PMID: 30360824 DOI: 10.1016/j.jacc.2018.09.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 09/01/2018] [Indexed: 10/28/2022]
Affiliation(s)
- Roxana Mehran
- Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
| | - Sabato Sorrentino
- Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Bimmer E Claessen
- Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
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34
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García-Compeán D, Del Cueto-Aguilera ÁN, Jiménez-Rodríguez AR, González-González JA, Maldonado-Garza HJ. Diagnostic and therapeutic challenges of gastrointestinal angiodysplasias: A critical review and view points. World J Gastroenterol 2019; 25:2549-2564. [PMID: 31210709 PMCID: PMC6558444 DOI: 10.3748/wjg.v25.i21.2549] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 04/19/2019] [Accepted: 04/29/2019] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal angiodysplasias (GIADs), also called angioectasias, are the most frequent vascular lesions. Its precise prevalence is unknown since most of them are asymptomatic. However, the incidence may be increasing since GIADs affect individuals aged more than 60 years and population life expectancy is globally increasing worldwide. They are responsible of about 5% to 10% of all gastrointestinal bleeding (GIB) cases. Most GIADs are placed in small bowel, where are the cause of 50 to 60% of obscure GIB diagnosed with video capsule endoscopy. They may be the cause of fatal severe bleeding episodes; nevertheless, recurrent overt or occult bleeding episodes requiring repeated expensive treatments and disturbing patient’s quality-of-life are more frequently observed. Diagnosis and treatment of GIADs (particularly those placed in small bowel) are a great challenge due to insidious disease behavior, inaccessibility to affected sites and limitations of available diagnostic procedures. Hemorrhagic causality out of the actively bleeding lesions detected by diagnostic procedures may be difficult to establish. No treatment guidelines are currently available, so there is a high variability in the management of these patients. In this review, the epidemiology and pathophysiology of GIADs and the status in the diagnosis and treatment, with special emphasis on small bowel angiodysplasias based on multiple publications, are critically discussed. In addition, a classification of GIADs based on their endoscopic characteristics is proposed. Finally, some aspects that need to be clarified in future research studies are highlighted.
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Affiliation(s)
- Diego García-Compeán
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital "Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Ángel N Del Cueto-Aguilera
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital "Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Alan R Jiménez-Rodríguez
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital "Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - José A González-González
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital "Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Héctor J Maldonado-Garza
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital "Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
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Abstract
Heyde described aortic stenosis and gastrointestinal bleeding in the 1950s. Since then, a link with intestinal angiodysplasia and abnormalities of von Willebrand factor (VWF) has been noted. Loss of the highest-molecular-weight multimers of VWF and bleeding also have been described in subaortic stenosis in hypertrophic cardiomyopathy, in isolated mitral and aortic insufficiency, in endocarditis, in patients with prosthetic valve stenosis or regurgitation, and in patients with left ventricular assist devices (LVADs). Bleeding tends to recur with local treatment of angiodysplasias, whereas cardiac repair or removal of LVAD eliminates VWF dysfunction is curative of bleeding in the majority.
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36
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Martinsson A, Li X, Torp-Pedersen C, Zöller B, Andell P, Andreasen C, Gislason G, Køber L, Sundquist K, Smith JG, Andersson C. Outcomes associated with dual antiplatelet therapy after myocardial infarction in patients with aortic stenosis. Int J Cardiol 2019; 281:140-145. [PMID: 30722957 DOI: 10.1016/j.ijcard.2019.01.063] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 12/12/2018] [Accepted: 01/16/2019] [Indexed: 11/30/2022]
Abstract
BACKGROUND Acquired loss of the largest von Willebrand factor multimers is a common hemostatic disturbance in patients with aortic valve stenosis (AS), resulting in impaired platelet adhesion and increased bleeding risk. AS is also associated with atherosclerosis and myocardial infarction (MI). Our aim was to study the clinical outcomes associated with AS in MI patients treated with dual antiplatelet therapy (DAPT) in a nationwide hospital-based register study. METHODS Based on nationwide hospital discharge registers from Sweden (2005-2010) and Denmark (2005-2015), we calculated 1-year incidence rates and hazard ratios of bleeding, recurrent MI, and all-cause mortality in MI patients with and without AS treated with DAPT. Results from both countries were also combined in a meta-analysis. RESULTS We included 50,460 MI patients from Sweden and 50,307 MI patients from Denmark, of which 3% had AS. The bleeding rates (per 100 person-years) in Sweden and Denmark were 3.2 and 3.3 among patients without AS vs. 9.2 and 8.3 among patients with AS. All-cause mortality rates were 7.1 vs. 28.7 in Sweden and 5.8 vs. 30.7 in Denmark among patients without and with AS, respectively. Patients with AS had an increased risk of bleeding, recurrent MI and all-cause mortality. Combined results from both countries were similar for bleeding (hazard ratio 1.59 [0.98-2.59]), recurrent MI (1.78 [1.25-2.54]), and all-cause mortality (1.76 [1.26-2.47]). CONCLUSION AS was associated with an increased risk of bleeding, recurrent MI and mortality after MI when treated with DAPT. Individualized selection of antiplatelet therapy may be warranted in this high-risk population.
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Affiliation(s)
- Andreas Martinsson
- Department of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden.
| | - Xinjun Li
- Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - Christian Torp-Pedersen
- Department of Health, Science and Technology, Aalborg University, Denmark; Department of Cardiology and Epidemiology/Biostatistics, Aalborg University Hospital, Denmark
| | - Bengt Zöller
- Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - Pontus Andell
- Department of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden
| | - Charlotte Andreasen
- Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark
| | - Gunnar Gislason
- Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark
| | - Lars Køber
- Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | | | - J Gustav Smith
- Department of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden
| | - Charlotte Andersson
- Department of Internal Medicine, Section of Cardiology, Copenhagen University Hospital Glostrup, Denmark
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37
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Horiuchi H, Doman T, Kokame K, Saiki Y, Matsumoto M. Acquired von Willebrand Syndrome Associated with Cardiovascular Diseases. J Atheroscler Thromb 2019; 26:303-314. [PMID: 30867356 PMCID: PMC6456452 DOI: 10.5551/jat.rv17031] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
The blood glycoprotein von Willebrand factor (VWF) plays an important role in hemostasis and thrombosis. VWF is produced and secreted as large multimers by endothelial cells and megakaryocytes. It is then cleaved in a sheer-stress dependent manner by a specific protease, ADAMTS13, into multimers consisting of 2–80 subunits. Among VWF multimers, high molecular weight (HMW) multimers play important roles in platelet aggregation. Therefore, their loss induces a hemostatic disorder known as von Willebrand disease (VWD) type 2A. Various cardiovascular diseases, such as aortic stenosis, hypertrophic obstructive cardiomyopathy (HOCM), and several congenital structural diseases, as well as mechanical circulatory support systems, generate excessive high shear stress in the bloodstream. These cause excessive cleavage of VWF multimers resulting in a loss of HMW multimers, known as acquired von Willebrand syndrome (AVWS), a hemostatic disorder similar to VWD type 2A. Bleeding often occurs in the gastrointestinal tract since a fragile angiodysplasia develops associated with these diseases. Radical treatment for AVWS is to remove the pathological high shear causing AVWS.
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Affiliation(s)
- Hisanori Horiuchi
- Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University
| | - Tsuyoshi Doman
- Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University
| | - Koichi Kokame
- Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center
| | - Yoshikatsu Saiki
- Division of Cardiovascular Surgery, Tohoku University Graduate School of Medicine
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Nagao K, Taniguchi T, Morimoto T, Shiomi H, Ando K, Kanamori N, Murata K, Kitai T, Kawase Y, Izumi C, Miyake M, Mitsuoka H, Kato M, Hirano Y, Matsuda S, Inada T, Murakami T, Takeuchi Y, Yamane K, Toyofuku M, Ishii M, Minamino-Muta E, Kato T, Inoko M, Ikeda T, Komasa A, Ishii K, Hotta K, Higashitani N, Kato Y, Inuzuka Y, Maeda C, Jinnai T, Morikami Y, Saito N, Minatoya K, Kimura T. Anemia in Patients with Severe Aortic Stenosis. Sci Rep 2019; 9:1924. [PMID: 30760807 PMCID: PMC6374463 DOI: 10.1038/s41598-018-36066-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 11/09/2018] [Indexed: 01/31/2023] Open
Abstract
Prognostic impact of anemia complicating severe aortic stenosis (AS) remains unclear. We assessed the impact of anemia on cardiovascular and bleeding outcomes in 3403 patients enrolled in the CURRENT AS registry. 835 patients (25%) had mild (hemoglobin 11.0–12.9 g/dl for men/11.0–11.9 g/dl for women) and 1282 patients (38%) had moderate/severe anemia (Hb ≤ 10.9 g/dl) at diagnosis of severe AS. Mild and moderate/severe anemia were associated with significantly increased risks relative to no anemia (hemoglobin ≥13.0 g/dl for men/≥12.0 g/dl for women) for the primary outcome measure (aortic valve-related death or heart failure hospitalization) in the entire population [hazard ratio (HR): 1.30; 95% confidence interval (CI): 1.07–1.57 and HR: 1.56; 95%CI: 1.31–1.87, respectively] and in the conservative management stratum (HR: 1.73; 95%CI: 1.40–2.13 and HR: 2.05; 95%CI: 1.69–2.47, respectively). Even in the initial aortic valve replacement stratum, moderate/severe anemia was associated with significantly increased risk for the primary outcome measure (HR: 2.12; 95%CI: 1.44–3.11). Moreover, moderate/severe anemia was associated with significantly increased risk for major bleeding while under conservative management (HR: 1.93; 95%CI: 1.21–3.06). These results warrant further study to explore whether better management of anemia would lead to improvement of clinical outcomes.
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Affiliation(s)
- Kazuya Nagao
- Cardiovascular Center, Osaka Red Cross Hospital, Osaka, Japan
| | - Tomohiko Taniguchi
- Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Takeshi Morimoto
- Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Hiroki Shiomi
- Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Kenji Ando
- Department of Cardiology, Kokura Memorial Hospital, Kokura, Japan
| | - Norio Kanamori
- Division of Cardiology, Shimada Municipal Hospital, Shimada, Japan
| | - Koichiro Murata
- Department of Cardiology, Shizuoka City Shizuoka Hospital, Shizuoka, Japan
| | - Takeshi Kitai
- Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Yuichi Kawase
- Department of Cardiovascular Medicine, Kurashiki Central Hospital, Kurashiki, Japan
| | - Chisato Izumi
- Department of Cardiology, Tenri Hospital, Tenri, Japan
| | - Makoto Miyake
- Department of Cardiology, Tenri Hospital, Tenri, Japan
| | - Hirokazu Mitsuoka
- Division of Cardiology, Nara Hospital, Kinki University Faculty of Medicine, Ikoma, Japan
| | - Masashi Kato
- Department of Cardiology, Mitsubishi Kyoto Hospital, Kyoto, Japan
| | - Yutaka Hirano
- Department of Cardiology, Kinki University Hospital, Osakasayama, Japan
| | - Shintaro Matsuda
- Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Tsukasa Inada
- Cardiovascular Center, Osaka Red Cross Hospital, Osaka, Japan
| | | | - Yasuyo Takeuchi
- Department of Cardiology, Shizuoka General Hospital, Shizuoka, Japan
| | | | - Mamoru Toyofuku
- Department of Cardiology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
| | - Mitsuru Ishii
- Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Eri Minamino-Muta
- Cardiovascular Center, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan
| | - Takao Kato
- Cardiovascular Center, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan
| | - Moriaki Inoko
- Cardiovascular Center, The Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan
| | - Tomoyuki Ikeda
- Department of Cardiology, Hikone Municipal Hospital, Hikone, Japan
| | - Akihiro Komasa
- Department of Cardiology, Kansai Electric Power Hospital, Osaka, Japan
| | - Katsuhisa Ishii
- Department of Cardiology, Kansai Electric Power Hospital, Osaka, Japan
| | - Kozo Hotta
- Department of Cardiology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan
| | | | - Yoshihiro Kato
- Department of Cardiology, Saiseikai Noe Hospital, Osaka, Japan
| | - Yasutaka Inuzuka
- Department of Cardiology, Shiga Medical Center for Adults, Moriyama, Japan
| | - Chiyo Maeda
- Department of Cardiology, Hamamatsu Rosai Hospital, Hamamatsu, Japan
| | - Toshikazu Jinnai
- Department of Cardiology, Japanese Red Cross Otsu Hospital, Otsu, Japan
| | - Yuko Morikami
- Department of Cardiology, Hirakata Kohsai Hospital, Hirakata, Japan
| | - Naritatsu Saito
- Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Kenji Minatoya
- Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Takeshi Kimura
- Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Rauch A, Susen S, Zieger B. Acquired von Willebrand Syndrome in Patients With Ventricular Assist Device. Front Med (Lausanne) 2019; 6:7. [PMID: 30805339 PMCID: PMC6371037 DOI: 10.3389/fmed.2019.00007] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Accepted: 01/11/2019] [Indexed: 01/27/2023] Open
Abstract
During the last decade the use of ventricular assist devices (VADs) for patients with severe heart failure has increased tremendously. However, flow disturbances, mainly high shear induced by the device is associated with bleeding complications. Shear stress-induced changes in VWF conformation are associated with a loss of high molecular weight multimers (HMW) of VWF and an increased risk of bleeding. This phenomenon and its cause will be elaborated and reviewed in the following.
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Affiliation(s)
- Antoine Rauch
- INSERM, U1011, Univ. Lille, U1011-EGID, Institut Pasteur de Lille, Lille, France.,CHU Lille, Hematology and Transfusion, Lille, France
| | - Sophie Susen
- INSERM, U1011, Univ. Lille, U1011-EGID, Institut Pasteur de Lille, Lille, France.,CHU Lille, Hematology and Transfusion, Lille, France
| | - Barbara Zieger
- Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Faculty of Medicine, Medical Center-University of Freiburg, University of Freiburg, Freiburg, Germany
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40
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Patel B, Shiani A, Rodriguez AC, Lipka S, Davis-Yadley AH, Nelson KK, Rabbanifard R, Kumar A, Brady PG. Outcomes in Patients with Left Ventricular Assist Devices, Pacemakers, and Implantable Cardioverter Defibrillators Undergoing Single Balloon Enteroscopy. South Med J 2019; 112:130-134. [PMID: 30708381 DOI: 10.14423/smj.0000000000000938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVES Obscure overt gastrointestinal bleeding can be challenging to evaluate in patients with electronic cardiac devices such as continuous flow left ventricular assist devices (LVADs), pacemakers (PPMs), and implantable cardioverter defibrillators (ICDs). Limited data exist on the utility and safety of single balloon enteroscopy (SBE) in patients with cardiac devices. We aimed to evaluate the safety, efficacy, diagnostic, and therapeutic outcomes of the aforementioned devices in patients undergoing SBE. METHODS A retrospective study was performed using the medical records of 57 patients undergoing SBE at our institution from 2010 to 2014. Patients were divided into two groups: those with cardiac devices and those without. Data on comorbidities, complications, findings, diagnostic, and therapeutic yield were compared. t Test and logistic regression assessed the association between dependent and independent variables. For continuous data, the results were summarized as mean difference and standard deviation. For dichotomous data, the results were summarized as odds ratio and 95% confidence intervals. RESULTS The overall age in patients with cardiac devices was 67.89 ± 6.96 versus 66.03 ± 11.95 years in the control. The cardiac device group was composed of 42.1% women; the control comprised 21.1% women. There were 19 patients with cardiac devices; 8 (LVAD + ICD), 1 (LVAD + PPM + ICD), 2 (PPM + ICD), 6 (PPM), 2 (ICD); 38 patients were in the control group. Patients with cardiac devices were hospitalized more often than patients without devices; this finding was not statistically significant (odds ratio 1.826, 95% confidence interval 0.544-6.128, P = 0.389). Procedure times were longer in the cardiac device group, 65.16 ± 49.92 minutes, when compared with the control, 57.40 ± 20.42, but it also did not reach statistical significance (mean difference 7.758, 95% confidence interval -11.360 to 26.876, P = 0.049). There was no statistically significant difference in major or minor events between patients with cardiac devices and the control group. Diagnostic and therapeutic yield and rebleeding rates were similar across both groups. CONCLUSIONS Patients in the cardiac device group did not appear to be at any more significant risk than those without cardiac devices. Furthermore, diagnostic and therapeutic yield and rebleeding rates appear to be similar across both groups. Clinicians may perform SBE in these patients safely and effectively, with good overall outcomes.
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Affiliation(s)
- Brijesh Patel
- From the Departments of Digestive Diseases and Nutrition, Internal Medicine, and Evidence-Based Medicine and Research Outcomes, University of South Florida, Tampa
| | - Ashok Shiani
- From the Departments of Digestive Diseases and Nutrition, Internal Medicine, and Evidence-Based Medicine and Research Outcomes, University of South Florida, Tampa
| | - Andrea C Rodriguez
- From the Departments of Digestive Diseases and Nutrition, Internal Medicine, and Evidence-Based Medicine and Research Outcomes, University of South Florida, Tampa
| | - Seth Lipka
- From the Departments of Digestive Diseases and Nutrition, Internal Medicine, and Evidence-Based Medicine and Research Outcomes, University of South Florida, Tampa
| | - Ashley H Davis-Yadley
- From the Departments of Digestive Diseases and Nutrition, Internal Medicine, and Evidence-Based Medicine and Research Outcomes, University of South Florida, Tampa
| | - Kirbylee K Nelson
- From the Departments of Digestive Diseases and Nutrition, Internal Medicine, and Evidence-Based Medicine and Research Outcomes, University of South Florida, Tampa
| | - Roshanak Rabbanifard
- From the Departments of Digestive Diseases and Nutrition, Internal Medicine, and Evidence-Based Medicine and Research Outcomes, University of South Florida, Tampa
| | - Ambuj Kumar
- From the Departments of Digestive Diseases and Nutrition, Internal Medicine, and Evidence-Based Medicine and Research Outcomes, University of South Florida, Tampa
| | - Patrick G Brady
- From the Departments of Digestive Diseases and Nutrition, Internal Medicine, and Evidence-Based Medicine and Research Outcomes, University of South Florida, Tampa
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Iyengar A, Sanaiha Y, Aguayo E, Seo YJ, Dobaria V, Toppen W, Shemin RJ, Benharash P. Comparison of Frequency of Late Gastrointestinal Bleeding With Transcatheter Versus Surgical Aortic Valve Replacement. Am J Cardiol 2018; 122:1727-1731. [PMID: 30316451 DOI: 10.1016/j.amjcard.2018.07.047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Revised: 07/22/2018] [Accepted: 07/31/2018] [Indexed: 12/17/2022]
Abstract
Improvements in technology and operator experience have led to exponential growth of transcatheter aortic valve implantation (TAVI) programs. Late bleeding complications were recently highlighted after TAVI with a high impact on morbidity. The purpose of the present study was to assess the incidence and financial impact of late Gastrointestinal (GI) bleeding after TAVI, and compare with the surgical cohort. Retrospective analysis of the National Readmissions Database was performed from January 2011 to December 2014, and patients who underwent TAVI or surgical aortic valve replacement (SAVR) were identified. Incidence of readmission with a diagnosis of GI bleeding was utilized as the primary end point. Overall, 43,357 patients were identified who underwent TAVI, whereas 310,013 patients underwent SAVR. Compared with SAVR, TAVI patients were older (81 vs 68y, p < 0.001), more women (48% vs 36%, p < 0.001), and had higher Elixhauser Comorbidity Index (6 vs 5, p < 0.001). Hospital stay was shorter with TAVI (5 vs 8 days, p < 0.001), but raw in-hospital mortality rates were similar (4.2% vs 3.8%, p = 0.022). In the TAVI cohort, 3.3% of patients were rehospitalized for GI bleeding compared with 1.5% of the SAVR cohort (p < 0.001). Average time to bleeding readmission was similar between cohorts (92 vs 84 days, p = 0.049). After multivariable adjustment, TAVI remained significantly associated with readmissions for GI bleeding compared with SAVR Adjusted Odds Ratio (AOR 1.54 [1.38 to 1.71], p < 0.001). In this national cohort study, TAVI was associated with more frequent readmissions for late GI bleeding compared with SAVR. In conclusion, strategies to reduce late GI bleeding may serve as important targets for improvement in overall quality of care.
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Affiliation(s)
- Amit Iyengar
- David Geffen School of Medicine, University of California, Los Angeles, CA.
| | - Yas Sanaiha
- Division of Cardiac Surgery, David Geffen School ofMedicine, University of California, Los Angeles, CA
| | - Esteban Aguayo
- David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Young-Ji Seo
- David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Vishal Dobaria
- Division of Cardiac Surgery, David Geffen School ofMedicine, University of California, Los Angeles, CA
| | - William Toppen
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA
| | - Richard J Shemin
- Division of Cardiac Surgery, David Geffen School ofMedicine, University of California, Los Angeles, CA
| | - Peyman Benharash
- Division of Cardiac Surgery, David Geffen School ofMedicine, University of California, Los Angeles, CA
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42
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Von Willebrand factor and the aortic valve: Concepts that are important in the transcatheter aortic valve replacement era. Thromb Res 2018; 170:20-27. [PMID: 30092557 DOI: 10.1016/j.thromres.2018.07.028] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2018] [Revised: 07/17/2018] [Accepted: 07/27/2018] [Indexed: 12/14/2022]
Abstract
Since the approval of the first transcatheter aortic valve replacement (TAVR) device in 2011, this technology has undergone substantial enhancements and exponential growth. However, valve thrombosis and residual paravalvular leaks (PVL) are among the challenges that require further investigation. Recently, monitoring von Willebrand factor (vWF) multimers has emerged as a tool to help evaluate the severity of PVL after TAVR. Following TAVR, vWF large multimers recovery have been documented. The role of large vWF multimers recovery and their interactions with platelets, and the endothelium have not been entirely elucidated. In this review, we discuss vWF synthesis and its role in aortic stenosis. We further provide an overview of the studies that investigated changes affecting vWF multimers following TAVR and the role of HMW vWF multimers monitoring in the determination of PVL severity. We also offer potential future directions for what will be fertile ground for research in this field.
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43
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Joly JM, El-Dabh A, Kirklin JK, Marshell R, Smith MG, Acharya D, Rajapreyar IN, Tallaj JA, Tresler M, Pamboukian SV. High Right Atrial Pressure and Low Pulse Pressure Predict Gastrointestinal Bleeding in Patients With Left Ventricular Assist Device. J Card Fail 2018; 24:487-493. [DOI: 10.1016/j.cardfail.2018.03.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Revised: 02/11/2018] [Accepted: 03/09/2018] [Indexed: 11/17/2022]
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44
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Mohee K, Aldalati O, Dworakowski R, Haboubi H. Aortic stenosis and anemia with an update on approaches to managing angiodysplasia in 2018. Cardiol J 2018; 27:72-77. [PMID: 30009379 DOI: 10.5603/cj.a2018.0068] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 06/11/2018] [Indexed: 11/25/2022] Open
Abstract
Angiodyplasia and aortic stenosis are both conditions that are highly prevalent in elderly people and can often co-exist. Recent studies suggest that this association is related to subtle alterations in plasma coagulation factors. The von Willebrand factor is the strongest link between aortic stenosis and bleeding associated with gastrointestinal angiodysplasia. With an ageing population, the disease burden of aortic stenosis and its association with angiodysplasia of the bowel makes this an incredibly underdiagnosed yet important condition. Clinicians should be aware of this association when dealing with elderly patients presenting either with unexplained anemia, gastrointestinal bleeding or with aortic stenosis. A high index of suspicion and appropriate diagnostic techniques followed by appropriate and prompt treatment could be life-saving. No clear guidelines exist on management but surgical aortic valve replacement is thought to offer the best hope for long-term resolution of bleeding. With a growing number of technological armamentarium in the management of such patients, especially with the advent of transcatheter aortic valve implantation, new options can be offered even to elderly patients with comorbidities for whom conventional surgery would have been impossible.
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Affiliation(s)
- Kevin Mohee
- Department of Cardiology, ABMU Health Board, Morriston Hospital, Swansea, SA6 6NL Swansea, United Kingdom
| | | | - Rafal Dworakowski
- Kings College London, London, United Kingdom. .,Department of Cardiology, Medical University of Gdansk, Poland.
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Vincent F, Rauch A, Loobuyck V, Moussa M, Juthier F, Debry N, Jeanpierre E, Lenting PJ, Susen S, Van Belle E. von Willebrand Factor for Aortic Valve Intervention. Circ Res 2018; 122:1499-1500. [DOI: 10.1161/circresaha.118.312859] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Flavien Vincent
- From the CHU Lille, Department of Cardiology, France (F.V., N.D., E.V.B.)
- University of Lille, Inserm U1011-EGID, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
- Institut Pasteur de Lille, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
| | - Antoine Rauch
- CHU Lille, Department of Hematology Transfusion, France (A.R., E.J., S.S.)
- University of Lille, Inserm U1011-EGID, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
- Institut Pasteur de Lille, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
| | - Valentin Loobuyck
- CHU Lille, Department of Cardiac Surgery, France (V.L., F.J.)
- University of Lille, Inserm U1011-EGID, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
- Institut Pasteur de Lille, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
| | - Mouhamed Moussa
- CHU Lille, Department of Anesthesia and Intensive Care, France (M.M.)
- University of Lille, Inserm U1011-EGID, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
- Institut Pasteur de Lille, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
| | - Francis Juthier
- CHU Lille, Department of Cardiac Surgery, France (V.L., F.J.)
- University of Lille, Inserm U1011-EGID, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
- Institut Pasteur de Lille, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
| | - Nicolas Debry
- From the CHU Lille, Department of Cardiology, France (F.V., N.D., E.V.B.)
| | | | - Peter J. Lenting
- Inserm, UMR-S 1176, University of Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France (P.J.L.)
| | - Sophie Susen
- CHU Lille, Department of Hematology Transfusion, France (A.R., E.J., S.S.)
- University of Lille, Inserm U1011-EGID, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
- Institut Pasteur de Lille, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
| | - Eric Van Belle
- From the CHU Lille, Department of Cardiology, France (F.V., N.D., E.V.B.)
- University of Lille, Inserm U1011-EGID, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
- Institut Pasteur de Lille, France (F.V., A.R., V.L., M.M., F.J., S.S., E.V.B.)
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Association of aortic valve disease with intestinal angioectasia: data from the Nationwide Inpatient Sample. Eur J Gastroenterol Hepatol 2018; 30:438-441. [PMID: 29369835 DOI: 10.1097/meg.0000000000001068] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
OBJECTIVE Since the description of a correlation between aortic stenosis and angioectasia, controversy has persisted about whether these diseases are truly associated or coincidental findings of older age. Our objective was to determine the association of aortic valve disease and bleeding intestinal angioectasia from a large database. PATIENTS AND METHODS We used the 2011 Nationwide Inpatient Sample database to identify hospitalizations in the USA in patients with bleeding intestinal angioectasia. International Classification of Diseases, 9th revision, Clinical Modification codes were used to identify patients with aortic valve disease, mitral valve disease, and known risk factors for angioectasia (including diagnosed von Willebrand disease, left ventricular assist device, and chronic kidney disease). Univariate and multivariate logistic regression were used to determine the odds of association between the valvular diseases and angioectasia. RESULTS A total of 32 079 intestinal angioectasia-related hospitalizations were identified of which 7.02% (n=2253) cases had coexistent aortic valve disease. The unadjusted odds of aortic valve disease in association with bleeding intestinal angioectasia versus those without bleeding angioectasia was 4.95 [95% confidence interval: (CI): 4.43-5.54, P<0.001]. The association of intestinal angioectasia with mitral valve disease was not significant (odds ratio=1.56, 95% CI: 0.59-4.14, P=0.38). When adjusted for age and known risk factors, the odds of aortic valve disease in bleeding intestinal angioectasia was still significant (odds ratio=2.37, 95% CI: 2.10-2.66, P<0.001). CONCLUSION Our findings support an important association between aortic valve disease and bleeding intestinal angioectasia, not identified in valvular heart valvular diseases with lower shear stress (mitral valve disease).
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Muslem R, Caliskan K, Leebeek FWG. Acquired coagulopathy in patients with left ventricular assist devices. J Thromb Haemost 2018; 16:429-440. [PMID: 29274191 DOI: 10.1111/jth.13933] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Indexed: 08/31/2023]
Abstract
Chronic heart failure (HF) is a major emerging healthcare problem, associated with a high morbidity and mortality. Left ventricular assist devices (LVADs) have emerged as a successful treatment option for patients with end-stage HF. Despite its great benefit, the use of LVAD is associated with a high risk of complications. Bleeding, pump thrombosis and thromboembolic events are frequently observed complications, with bleeding complications occurring in over a third of the patients. Although the design of the third-generation LVAD has improved greatly, these hemostatic complications still occur. The introduction of an LVAD into the circulatory system results in an altered hematological balance as a consequence of blood-pump interactions, changes in hemodynamics, the rheology, and the concomitant need for anticoagulation while implanted with an LVAD. The majority, if not all, LVAD patients experience a form of platelet dysfunction and impaired von Willebrand factor activity, leading to acquired coagulopathy disorders. Different diagnostic tools and treatment strategies have been reported; however, they require validation in LVAD patients. The present review focuses on acquired coagulopathies, describing the incidence, impact and underlying mechanism of acquired coagulopathy disorders in patients supported by LVADs. In addition, we will discuss diagnostic and management strategies for these acquired coagulopathies.
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Affiliation(s)
- R Muslem
- Department of Cardiothoracic Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
- Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - K Caliskan
- Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - F W G Leebeek
- Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
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Yasar SJ, Abdullah O, Fay W, Balla S. Von Willebrand factor revisited. J Interv Cardiol 2017; 31:360-367. [PMID: 29285810 DOI: 10.1111/joic.12478] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 11/12/2017] [Accepted: 11/13/2017] [Indexed: 01/18/2023] Open
Abstract
Degenerative aortic valve stenosis is the most common valvular heart disease seen in developed countries. Since the implementation of transcatheter aortic valve replacement, there has been a surge of efforts to improve procedural technique as well as reduce mortality. Until recently, the mainstay method of assessment of valve implantation as well as paravalvular regurgitation has relied heavily on imaging techniques including transesophageal echocardiography and aortic root angiography. There has been a lot of scientific inquiry to identify biomarkers in the management of patients with aortic stenosis. von Willebrand factor activity and high molecular weight multimer level assessment has emerged as an excellent biomarker with intraoperative, point of care potential. These implications can both supplement imaging modalities as well as potentially serve as a more accurate assessment TAVR complications.
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Affiliation(s)
| | | | - William Fay
- University of Missouri, Columbia, MissouriMissouri
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Balbo CP, Seabra LP, Galoro VG, Caputi G, Palma JH, Buffolo Ê. Heyde's Syndrome and Transcatheter Aortic Valve Implantation. Arq Bras Cardiol 2017; 108:378-380. [PMID: 28538766 PMCID: PMC5421479 DOI: 10.5935/abc.20160193] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Accepted: 04/04/2016] [Indexed: 01/25/2023] Open
Affiliation(s)
| | | | | | - Guido Caputi
- Hospital do Coração da Associação Sanatório Sírio, São Paulo, SP - Brazil
| | - José Honório Palma
- Hospital do Coração da Associação Sanatório Sírio, São Paulo, SP - Brazil
| | - Ênio Buffolo
- Hospital do Coração da Associação Sanatório Sírio, São Paulo, SP - Brazil
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Sponga S, Pontara E, Cattini MG, Basso C, Thiene G, Cella G, Daidone V, Gerosa G, Pagnan A, Casonato A. von Willebrand factor abnormalities in aortic valve stenosis: Pathophysiology and impact on bleeding. Thromb Haemost 2017; 106:58-66. [DOI: 10.1160/th10-10-0634] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2010] [Accepted: 03/14/2011] [Indexed: 11/05/2022]
Abstract
SummaryAcquired von Willebrand syndrome (AVWS) may complicate severe aortic valve stenosis, due to a reduction in the haemostatically more efficient large von Willebrand factor (VWF) multimers. This study was designed to analyse the relevance of VWF abnormalities and haemorrhagic diathesis in severe aortic valve stenosis. Forty-one consecutive patients undergoing valve replacement were investigated: seven had minor bleeding symptoms in their recent history; 10 (24.3%) had a reduced VWF collagen binding (VWF:CB) to VWF antigen ratio, and 33 (80.5%) had a decrease in large VWF multimers. The shortage of large multimers was not associated with any accumulation of small VWF multimers (apparently ruling out any increased VWF proteolysis), nor was there any increase in VWF propeptide, which excludes a shorter VWF survival. The risk of developing VWF abnormalities was higher in patients with rheumatic valve disease than in degenerative cases (p=0.025) and in valves with <50% of residual endothelial cells (p=0.004). Bleeders differed from non-bleeders in that they had a higher mean transvalvular gradient and a more marked decrease in large VWF multimers. VWF abnormalities did not exacerbate peri-operative blood loss, however – a finding consistent with the full correction of these VWF abnormalities, seen already on the first postoperative day and persisting for up to six months after surgery. According to the data obtained in our cohort of patients VWF abnormalities are common in severe aortic stenosis, particularly in cases of rheumatic valve disease, but loss of the largest multimers does not seem to cause clinical bleeding in most patients.
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