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Hamiko M, Gerdes L, Silaschi M, Seidel H, Westhofen P, Kruppenbacher J, Hertfelder HJ, Oldenburg J, Bakhtiary F, Velten M, Oezkur M, Duerr GD. Investigation of von Willebrand factor multimer abnormalities before and after aortic valve replacement using the Hydragel-5 assay. Thromb Res 2024; 241:109094. [PMID: 38991494 DOI: 10.1016/j.thromres.2024.109094] [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: 02/08/2024] [Revised: 06/24/2024] [Accepted: 07/05/2024] [Indexed: 07/13/2024]
Abstract
BACKGROUND Severe aortic stenosis (sAS) is associated with acquired von Willebrand syndrome (AVWS) by loss of high-molecular-weight multimers (HMWM) of von Willebrand factor (VWF), potentially resulting in perioperative bleeding. Analysis of VWF multimers remains challenging. Recently, the new, rapid Hydragel 5 assay has been developed, using electrophoretic protein separation for dividing VWF-multimers into low (LMWM), intermediate (IMWM), and HMWM, the hemostatically active part of VWF. Here, we evaluated its impact on predicting blood loss in presence of AVWS after surgical aortic valve replacement (SAVR). METHODS We prospectively examined 52 patients (age: 68 ± 7 years; 54 % male) admitted to SAVR. They were divided in two groups (A: normal VWF, n = 28; B: abnormal VWF, n = 24, defined as VWF-activity/antigen (VWF:Ac/Ag)-ratio < 0.7 and/or HMWM loss). Blood samples and echocardiographic data were collected before, seven days and three months after SAVR. Blood loss and transfusions were recorded. RESULTS Baseline characteristics and clinical data were similar in both groups. HMWM loss was present in 38.5 % of all patients. HMWM, the VWF:Ac/Ag- and HMWM/(IMWM+LMWM)-ratios were significantly decreased preoperatively in group B but normalized after SAVR. Bleeding, re-thoracotomy and transfusion rates were comparable. HMWM loss was inversely correlated with the peak aortic gradient (Pmax) and positively with the aortic valve area (AVA), while HMWM/(IMWM+LMWM)-ratio negatively correlated with the mean aortic gradient (Pmean). CONCLUSION HMWM and HMWM/(IMWM+LMWM)-ratio inversely correlate with severity of AS and normalize after SAVR. The Hydragel-5 assay's might be valuable for routine diagnostics to assess bleeding risk and postoperative normalization of AS and VWF abnormalities in SAVR patients.
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Affiliation(s)
- Marwan Hamiko
- Department of Cardiac Surgery, University Hospital Bonn, Bonn, Germany
| | - Lena Gerdes
- Department of Cardiac Surgery, University Hospital Bonn, Bonn, Germany
| | - Miriam Silaschi
- Department of Cardiac Surgery, University Hospital Bonn, Bonn, Germany
| | - Holger Seidel
- Center for Bleeding Disorders and Transfusion Medicine, (CBT), Bonn, Germany
| | - Philipp Westhofen
- Center for Bleeding Disorders and Transfusion Medicine, (CBT), Bonn, Germany
| | | | - Hans-Joerg Hertfelder
- Center for Bleeding Disorders and Transfusion Medicine, (CBT), Bonn, Germany; Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany
| | - Johannes Oldenburg
- Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany
| | - Farhad Bakhtiary
- Department of Cardiac Surgery, University Hospital Bonn, Bonn, Germany
| | - Markus Velten
- Department of Anesthesiology and Pain Management, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Mehmet Oezkur
- Department of Cardiovascular Surgery, University Medical Center, Johannes-Gutenberg University, Mainz, Germany
| | - Georg Daniel Duerr
- Department of Cardiovascular Surgery, University Medical Center, Johannes-Gutenberg University, Mainz, Germany
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Ledergerber K, Hollinger A, Zimmermann S, Todorov A, Trutmann M, Gallachi L, Gschwandtner LA, Ryser LA, Gebhard CE, Bolliger D, Buser A, Tsakiris DA, Siegemund M. Impact of Additional Administration of von Willebrand Factor Concentrates to Thrombocyte Transfusion in Perioperative Bleeding in Cardiac Surgery. Transfus Med Hemother 2024; 51:22-31. [PMID: 38314243 PMCID: PMC10836859 DOI: 10.1159/000530810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 04/16/2023] [Indexed: 02/06/2024] Open
Abstract
Background Von Willebrand factor (vWF) is an important part of blood coagulation since it binds platelets to each other and to endothelial cells. In traumatic and surgical haemorrhage, both blood cells and plasmatic factors are consumed, leading to consumption coagulopathy and fluid resuscitation. This often results in large amounts of crystalloids and blood products being infused. Additional administration of vWF complex and platelets might mitigate this problem. We hypothesize that administration of vWF concentrate additionally to platelet concentrates reduces blood loss and the amount of blood products (platelets, red blood cells [RBC], fresh frozen plasma [FFP]) administered. Methods We conducted a monocentric 6-year retrospective data analysis of cardiac surgery patients. Included were all patients receiving platelet concentrates within 48 h postoperatively. Patients who additionally received vWF concentrates were allocated to the intervention group and all others to the control group. Groups were compared in mixed regression models correcting for known confounders, based on nearest neighbour propensity score matching. Primary endpoints were loss of blood (day one and two) and amount of needed blood products on day one and two (platelets, RBC, FFP). Secondary endpoints were intensive care unit (ICU) and in-hospital length of stay, ICU and in-hospital mortality, and absolute difference of platelet counts before and after treatment. Results Of 497 patients analysed, 168 (34%) received vWF concentrates. 121 patients in both groups were considered for nearest neighbour matching. Patients receiving additional vWF were more likely to receive more blood products (RBC, FFP, platelets) in the first 24 h after surgery and had around 200 mL more blood loss at the same time. Conclusion In this retrospective analysis, no benefit in additional administration of vWF to platelet concentrates on perioperative blood loss, transfusion requirement (platelets, RBC, FFP), length of stay, and mortality could be found. These findings should be verified in a prospective randomized controlled clinical trial (www.clinicaltrials.gov identifier NCT04555785).
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Affiliation(s)
| | - Alexa Hollinger
- Intensive Care Unit, University Hospital Basel, Basel, Switzerland
- Medical Faculty, University of Basel, Basel, Switzerland
| | | | - Atanas Todorov
- Cardiovascular Gender Medicine, University Hospital Zürich, Zürich, Switzerland
| | - Maren Trutmann
- Intensive Care Unit, University Hospital Basel, Basel, Switzerland
| | - Laura Gallachi
- Intensive Care Unit, University Hospital Basel, Basel, Switzerland
| | | | | | - Caroline Eva Gebhard
- Intensive Care Unit, University Hospital Basel, Basel, Switzerland
- Medical Faculty, University of Basel, Basel, Switzerland
| | - Daniel Bolliger
- Medical Faculty, University of Basel, Basel, Switzerland
- Department of Anesthesiology, University Hospital Basel, Basel, Switzerland
| | - Andreas Buser
- Medical Faculty, University of Basel, Basel, Switzerland
- Department of Anesthesiology, University Hospital Basel, Basel, Switzerland
- Regional Blood Transfusion Service of the Swiss Red Cross, Basel, Switzerland
| | - Dimitrios Athanasios Tsakiris
- Medical Faculty, University of Basel, Basel, Switzerland
- Department of Transfusion Medicine and Hematology, Basel University Hospital, Basel, Switzerland
| | - Martin Siegemund
- Intensive Care Unit, University Hospital Basel, Basel, Switzerland
- Medical Faculty, University of Basel, Basel, Switzerland
- Department of Clinical Research, University of Basel, Basel, Switzerland
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Sun GH, Ortoleva JP, Lu SY, Vanneman MW, Tanaka K, Mazzeffi M, Dalia AA. ABO Blood Group and Bleeding and Survival in VA-ECMO Patients. J Intensive Care Med 2023; 38:1015-1022. [PMID: 37291851 DOI: 10.1177/08850666231178759] [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] [Indexed: 06/10/2023]
Abstract
ABO blood group has been shown to be a major determinant of plasma von Willebrand factor (vWF) levels. O blood group is associated with the lowest vWF levels and confers an increased risk of hemorrhagic events, while AB blood group has the highest levels and is associated with thromboembolic events. We hypothesized in extracorporeal membrane oxygenation (ECMO) patients that O blood type would have the highest and AB blood type would have the lowest transfusions, with an inverse relationship to survival. A retrospective analysis of 307 VA-ECMO patients at a major quaternary referral hospital was performed. The distribution of blood groups included 124 group O (40%), 122 group A (40%), 44 group B (14%), and 17 group AB (6%) patients. Regarding usage of packed red blood cells, fresh frozen plasma, and platelets, there was a non-statistically significant difference in transfusions, with group O having the least and group AB having the most requirements. However, there was a statistically significant difference in cryoprecipitate usage when comparing to group O: group A (1.77, 95% CI: 1.05-2.97, P < .05), group B (2.05, 95% CI: 1.16-3.63, P < .05), and group AB (3.43, 95% CI: 1.71-6.90, P < .001). Furthermore, a 20% increase in length of days on ECMO was associated with a 2-12% increase in blood product usage. The cumulative 30-day mortality rate for groups O and A was 60%, group B was 50%, and group AB was 40%; the 1-year mortality rate for groups O and A was 65%, group B was 57%, and group AB was 41%; however, the mortality differences were not statistically significant.
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Affiliation(s)
- Gina H Sun
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Jamel P Ortoleva
- Department of Anesthesiology and Perioperative Medicine, Tufts Medical Center, Boston, MA, USA
| | - Shu Y Lu
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Matthew W Vanneman
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford Hospital, Palo Alto, CA, USA
| | - Kenichi Tanaka
- Department of Anesthesiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Michael Mazzeffi
- Department of Anesthesiology, University of Virginia Health University Hospital, Charlottesville, VA, USA
| | - Adam A Dalia
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA
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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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Ramesh P, Kanagalingam S, Zargham Ul Haq F, Victory Srinivasan N, Khan AI, Mashat GD, Hazique M, Khan KI, Khan S. Acquired Von Willebrand Deficiency in Adults With Aortic Stenosis: A Systematic Review. Cureus 2022; 14:e28879. [PMID: 36225403 PMCID: PMC9541123 DOI: 10.7759/cureus.28879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 09/07/2022] [Indexed: 11/16/2022] Open
Abstract
Von Willebrand factor (VWF) deficiency is associated with bleeding complications. The congenital type of Von Willebrand disease(VWD) is a very well-known bleeding disorder and sometimes may be associated with life-threatening hemorrhage. This systematic review is aimed at gathering further knowledge regarding the pathology of an acquired VWD form within a population of patients with aortic stenosis (AS) by shortlisting quality articles on this theme, through the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 guidelines. High shear stress caused by the stenotic valve cleaves VWF multimers, causing a relative state of deficiency. The condition returns to baseline immediately following surgical replacement of the valve. Results across eight studies reviewed by a majority concluded that in an AS patient with bleeding, the most likely cause is an acquired deficiency of VWF, associated with factors influencing blood flow and caused by the in-situ valve. However, several studies suggested otherwise/were misclassifications. This review highlighted the relationship between AS and acquired VWF deficiency and should be foreseen as an adverse complication, attracting further research and future theragnostic strategies for this condition.
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Affiliation(s)
- Prasana Ramesh
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | | | - Fnu Zargham Ul Haq
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | | | - Aujala Irfan Khan
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Ghadi D Mashat
- Pediatrics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Mohammad Hazique
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Kokab Irfan Khan
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Zhang Y, Jiang F, Chen Y, Ju LA. Platelet Mechanobiology Inspired Microdevices: From Hematological Function Tests to Disease and Drug Screening. Front Pharmacol 2022; 12:779753. [PMID: 35126120 PMCID: PMC8811026 DOI: 10.3389/fphar.2021.779753] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Accepted: 12/28/2021] [Indexed: 12/30/2022] Open
Abstract
Platelet function tests are essential to profile platelet dysfunction and dysregulation in hemostasis and thrombosis. Clinically they provide critical guidance to the patient management and therapeutic evaluation. Recently, the biomechanical effects induced by hemodynamic and contractile forces on platelet functions attracted increasing attention. Unfortunately, the existing platelet function tests on the market do not sufficiently incorporate the topical platelet mechanobiology at play. Besides, they are often expensive and bulky systems that require large sample volumes and long processing time. To this end, numerous novel microfluidic technologies emerge to mimic vascular anatomies, incorporate hemodynamic parameters and recapitulate platelet mechanobiology. These miniaturized and cost-efficient microfluidic devices shed light on high-throughput, rapid and scalable platelet function testing, hematological disorder profiling and antiplatelet drug screening. Moreover, the existing antiplatelet drugs often have suboptimal efficacy while incurring several adverse bleeding side effects on certain individuals. Encouraged by a few microfluidic systems that are successfully commercialized and applied to clinical practices, the microfluidics that incorporate platelet mechanobiology hold great potential as handy, efficient, and inexpensive point-of-care tools for patient monitoring and therapeutic evaluation. Hereby, we first summarize the conventional and commercially available platelet function tests. Then we highlight the recent advances of platelet mechanobiology inspired microfluidic technologies. Last but not least, we discuss their future potential of microfluidics as point-of-care tools for platelet function test and antiplatelet drug screening.
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Affiliation(s)
- Yingqi Zhang
- School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, Sydney, NSW, Australia
- Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia
- Heart Research Institute, Newtown, NSW, Australia
| | - Fengtao Jiang
- School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, Sydney, NSW, Australia
| | - Yunfeng Chen
- The Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, United States
- The Department of Pathology, The University of Texas Medical Branch, Galveston, TX, United States
| | - Lining Arnold Ju
- School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, Sydney, NSW, Australia
- Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia
- Heart Research Institute, Newtown, NSW, Australia
- *Correspondence: Lining Arnold Ju,
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Mazur P, Natorska J, Ząbczyk M, Krzych Ł, Litwinowicz R, Kędziora A, Kapelak B, Undas A. Von Willebrand factor in aortic or mitral valve stenosis and bleeding after heart valve surgery. Thromb Res 2020; 198:190-195. [PMID: 33360153 DOI: 10.1016/j.thromres.2020.12.005] [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: 08/21/2020] [Revised: 10/05/2020] [Accepted: 12/09/2020] [Indexed: 11/25/2022]
Abstract
OBJECTIVES Low von Willebrand factor (VWF) increases the risk of bleeding. The objective was to assess the influence of VWF on bleeding after valvular surgery. METHODS We studied 82 consecutive patients in median age of 65.5 years with severe isolated aortic stenosis (AS, n = 62) or mitral stenosis (MS, n = 20), undergoing heart valve surgery in extracorporeal circulation. Preoperatively, we assessed VWF antigen (VWF:Ag) and activity (VWF:RCo), a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), and fibrinolysis inhibitors. RESULTS Compared with AS, MS patients were more frequently female (80 vs. 55%, p = 0.045) with atrial fibrillation (AF) (80 vs. 8%, p < 0.0001), with no difference in age or comorbidities. Median postoperative drainage was 420 ml for AS, and 425 ml for MS (p = 0.37). Patients with AS had lower VWF:RCo (125.8 [88.5-160.8] vs. 188.0 [140.3-207.3] IU/dl, p = 0.003) and VWF:Ag (135.8 [112.0-171.2] vs. 191.7 [147.3-236.4] IU/dl, p = 0.01) than MS patients. Mean VWF:RCo/Ag ratio was 0.88 ± 0.17, with no intergroup differences. ADAMTS13 levels and activity were similar in both groups. In AS, both VWF:RCo and VWF:Ag correlated inversely with maximal (r = -0.39, p = 0.0003 and r = -0.39, p = 0.0004, respectively) and mean (r = -0.40, p = 0.0004 and r = -0.39, p = 0.0006, respectively) transvalvular pressure gradients. There was no difference in perioperative bleeding between patients following mitral and aortic valve surgery, and bleeding was not associated with VWF:Ag or VWF:RCo. CONCLUSIONS In severe AS, VWF levels and activity correlate inversely with transvalvular pressure gradients, and are lower than in severe degenerative MS, but do not affect blood loss after valvular surgery in extracorporeal circulation.
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Affiliation(s)
- Piotr Mazur
- Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; The John Paul II Hospital, Krakow, Poland.
| | - Joanna Natorska
- Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; The John Paul II Hospital, Krakow, Poland
| | - Michał Ząbczyk
- Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; The John Paul II Hospital, Krakow, Poland
| | - Łukasz Krzych
- Department of Anaesthesiology and Intensive Care, Medical University of Silesia, Katowice, Poland
| | - Radosław Litwinowicz
- Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; The John Paul II Hospital, Krakow, Poland
| | | | - Bogusław Kapelak
- Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; The John Paul II Hospital, Krakow, Poland
| | - Anetta Undas
- Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland; The John Paul II Hospital, Krakow, Poland
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Mondal S, Hollander KN, Ibekwe SO, Williams B, Tanaka K. Heyde Syndrome-Pathophysiology and Perioperative Implications. J Cardiothorac Vasc Anesth 2020; 35:3331-3339. [PMID: 33132021 DOI: 10.1053/j.jvca.2020.10.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 10/02/2020] [Accepted: 10/04/2020] [Indexed: 11/11/2022]
Abstract
Gastrointestinal (GI) bleeding in patients with calcific aortic valve stenosis (AVS), termed Heyde syndrome, was first described by Edward C. Heyde. The strong association between valvular replacement and the eradication of clinically significant GI bleeding confirmed an underlying pathophysiologic relationship. The rheologic stress created by AVS increases proteolysis of von Willebrand factor (VWF), resulting in loss of predominantly high-molecular-weight VWF (Hmw VWF). Angiodysplastic vessels present in patients with AVS, coupled with the lack of functioning Hmw VWF, increase the risk for GI bleeds. Aortic valve replacement, both surgical and transcatheter-based, is often a definitive treatment for GI bleeding, leading to recovery of Hmw VWF multimers. Perioperative management of patients involves monitoring their coagulation profiles with relevant laboratory tests and instituting appropriate management. Management can be directed in the following two ways: by improving internal release of VWF or by administration of external therapeutics containing VWF. It is important for perioperative physicians to obtain an understanding of the pathophysiology of this disease process and closely monitor the bleeding pattern so that targeted therapies can be initiated.
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Affiliation(s)
- Samhati Mondal
- Department of Anesthesiology, Cardiac Anesthesia Division, University of Maryland School of Medicine, Baltimore, MD.
| | - Kimberly N Hollander
- Department of Anesthesiology, Cardiac Anesthesia Division, University of Maryland School of Medicine, Baltimore, MD
| | - Stephanie O Ibekwe
- Department of Anesthesiology, Cardiovascular Division, BTGH, Baylor College of Medicine, Houston, TX
| | - Brittney Williams
- Department of Anesthesiology, Cardiac Anesthesia Division, University of Maryland School of Medicine, Baltimore, MD
| | - Kenichi Tanaka
- Department of Anesthesiology, Cardiac Anesthesia Division, University of Maryland School of Medicine, Baltimore, MD
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9
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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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10
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Pre-procedural abnormal function of von Willebrand Factor is predictive of bleeding after surgical but not transcatheter aortic valve replacement. J Thromb Thrombolysis 2020; 48:610-618. [PMID: 31359325 PMCID: PMC6800844 DOI: 10.1007/s11239-019-01917-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
Both transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) have been proven to effectively correct von Willebrand Factor (vWF) pathologies, however there is limited data simultaneously comparing outcomes of both approaches. We prospectively enrolled patients with severe aortic stenosis referred for TAVI (n = 52) or SAVR (n = 48). In each case, vWF antigen (vWF:Ag), vWF activity (vWF:Ac) and activity-to-antigen (vWF:Ac/Ag) ratio were assessed at baseline, 24 h and 72 h after procedure. VWF abnormalities were defined as reduced vWF:Ac/Ag ratio (< 0.8). Bleeding events in both arms were classified according to Valve Academic Research Consortium (VARC-2) definitions. Overall, there was no difference between patients referred for TAVI and SAVR in vWF:Ac (1.62 ± 0.52 vs 1.71 ± 0.64; p = 0.593), vWF:Ag (1.99 ± 0.81 vs 2.04 ± 0.81; p = 0.942) or vWF:Ac/Ag ratio (0.84 ± 0.16 vs 0.85 ± 0.12; p = 0.950). Pathological vWF:Ac/Ag ratio was found in 20 (38%) TAVI and 15 (31%) SAVR patients (p = 0.407). Normalization of vWF:Ac/Ag ratio at day 3 after procedure was achieved in 19 (95%) TAVI and 13 (87%) SAVR patients (p = 0.439). Similar prevalence of major or life-threatening bleedings (MLTB) after TAVI and SAVR in entire groups was observed (19% vs. 23%, p = 0.652). VWF abnormalities were associated with higher incidence of MLTB in SAVR (53% vs 9%, p < 0.001), but not TAVI (15% vs. 22%, p = 0.132). Accordingly, in receiver-operating characteristic curve analysis vWF:Ac/Ag ratio < 0.8 showed significant sensitivity and specificity for predicting MLTB in SAVR group (AUC 0.735, 95% CI 0.538–0.931, p = 0.019). We proved that abnormal function of vWF is corrected successfully after both TAVI and SAVR, but vWF abnormalities are predictive of MLTB only in surgical patients.
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11
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Zindovic I, Sjögren J, Bjursten H, Ingemansson R, Larsson M, Svensson PJ, Strandberg K, Wierup P, Nozohoor S. The role of von Willebrand factor in acute type A aortic dissection and aortic surgery. Thromb Res 2019; 178:139-144. [DOI: 10.1016/j.thromres.2019.04.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 03/06/2019] [Accepted: 04/15/2019] [Indexed: 01/11/2023]
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12
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Henderson RA, Mazzeffi MA, Strauss ER, Williams B, Wipfli C, Dawood M, Taylor BS, Tanaka KA. Impact of intraoperative high‐volume autologous blood collection on allogeneic transfusion during and after cardiac surgery: a propensity score matched analysis. Transfusion 2019; 59:2023-2029. [DOI: 10.1111/trf.15253] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Revised: 02/01/2019] [Accepted: 02/03/2019] [Indexed: 11/29/2022]
Affiliation(s)
- Reney A. Henderson
- Division of Cardiovascular Anesthesia, Department of SurgeryUniversity of Maryland School of Medicine Baltimore Maryland
| | - Michael A. Mazzeffi
- Division of Cardiovascular Anesthesia, Department of SurgeryUniversity of Maryland School of Medicine Baltimore Maryland
| | - Erik R. Strauss
- Division of Cardiovascular Anesthesia, Department of SurgeryUniversity of Maryland School of Medicine Baltimore Maryland
| | - Brittney Williams
- Division of Cardiovascular Anesthesia, Department of SurgeryUniversity of Maryland School of Medicine Baltimore Maryland
| | - Camron Wipfli
- Division of Cardiovascular Anesthesia, Department of SurgeryUniversity of Maryland School of Medicine Baltimore Maryland
| | - Murtaza Dawood
- Division of Cardiovascular Anesthesia, Department of SurgeryUniversity of Maryland School of Medicine Baltimore Maryland
| | - Bradley S. Taylor
- Division of Cardiac Surgery, Department of SurgeryUniversity of Maryland School of Medicine Baltimore Maryland
| | - Kenichi A. Tanaka
- Division of Cardiovascular Anesthesia, Department of SurgeryUniversity of Maryland School of Medicine Baltimore Maryland
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13
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Brandenburger C, Unislawski V, Budde U, Zittermann A, Gummert J, Knabbe C, Birschmann I. The von Willebrand factor ratio and perioperative bleeding in patients with aortic valve stenosis. THE JOURNAL OF CARDIOVASCULAR SURGERY 2019. [DOI: 10.23736/s0021-9509.18.10209-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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14
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Jhun CS, Siedlecki C, Xu L, Lukic B, Newswanger R, Yeager E, Reibson J, Cysyk J, Weiss W, Rosenberg G. Stress and Exposure Time on von Willebrand Factor Degradation. Artif Organs 2018; 43:199-206. [PMID: 30374981 DOI: 10.1111/aor.13323] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 05/14/2018] [Accepted: 06/22/2018] [Indexed: 12/13/2022]
Abstract
Despite the prevailing use of the continuous flow left ventricular assist devices (cf-LVAD), acquired von Willebrand syndrome (AvWS) associated with cf-LVAD still remains a major complication. As AvWS is known to be dependent on shear stress (τ) and exposure time (texp ), this study examined the degradation of high molecular weight multimers (HMWM) of von Willebrand factor (vWF) in terms of τ and texp . Two custom apparatus, i.e., capillary-tubing-type degrader (CTD) and Taylor-Couette-type degrader (TCD) were developed for short-term (0.033 sec ≤ texp ≤ 1.05 s) and long-term (10 s ≤ texp ≤ 10 min) shear exposures of vWF, respectively. Flow conditions indexed by Reynolds number (Re) for CTD were 14 ≤ Re ≤ 288 with corresponding laminar stress level of 52 ≤ τ CTD ≤ 1042 dyne/cm2 . Flow conditions for TCD were 100 ≤ Re ≤ 2500 with corresponding rotor speed of 180 ≤ o ≤ 4000 RPM and laminar stress level of 50 ≤ τ TCD ≤ 1114 dyne/cm2 . Due to transitional and turbulent flows in TCD at Re > 1117, total stress (i.e., τ total = laminar + turbulent) was also calculated using a computational fluid dynamics (CFD) solver, Converge CFD (Converge Science Inc., Madison, WI, USA). Inhibition of ADAMTS13 with different concentration of EDTA (5 mM and 10 mM) was also performed to investigate the mechanism of cleavage in terms of mechanical and enzymatic aspects. Degradation of HMWM with CTD was negligible at all given testing conditions. Although no degradation of HMWM was observed with TCD at Re < 1117 ( τ total = 1012 dyne/cm2 ), increase in degradation of HMWM was observed beyond Re of 1117 for all given exposure times. At Re ~ 2500 ( τ total = 3070 dyne/cm2 ) with texp = 60 s, a severe degradation of HMWM (90.7 ± 3.8%, abnormal) was observed, and almost complete degradation of HMWM (96.1 ± 1.9%, abnormal) was observed with texp = 600 s. The inhibition studies with 5 mM EDTA at Re ~ 2500 showed that loss of HMWM was negligible (<10%, normal) for all given exposure times except for texp = 10 min (39.5 ± 22.3%, borderline-abnormal). With 10 mM EDTA, no degradation of HMWM was observed (11.1 ± 4.4%, normal) even for texp = 10 min. This study investigated the effect of shear stress and exposure time on the HMWM of vWF in laminar and turbulent flows. The inhibition study by EDTA confirms that degradation of HMWM is initiated by shear-induced unfolding followed by enzymatic cleavage at given conditions. Determination of magnitude of each mechanism needs further investigation. It is also important to note that the degradation of vWF is highly dependent on turbulence regardless of the time exposed within our testing conditions.
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Affiliation(s)
- Choon-Sik Jhun
- Division of Applied Biomedical Engineering, Department of Surgery, Penn State College of Medicine, Hershey PA, USA
| | - Christopher Siedlecki
- Division of Applied Biomedical Engineering, Department of Surgery, Penn State College of Medicine, Hershey PA, USA.,Department of Biomedical Engineering, Penn State University, University Park, PA, USA
| | - Lichong Xu
- Division of Applied Biomedical Engineering, Department of Surgery, Penn State College of Medicine, Hershey PA, USA
| | - Branka Lukic
- Division of Applied Biomedical Engineering, Department of Surgery, Penn State College of Medicine, Hershey PA, USA
| | - Raymond Newswanger
- Division of Applied Biomedical Engineering, Department of Surgery, Penn State College of Medicine, Hershey PA, USA
| | - Eric Yeager
- Division of Applied Biomedical Engineering, Department of Surgery, Penn State College of Medicine, Hershey PA, USA
| | - John Reibson
- Division of Applied Biomedical Engineering, Department of Surgery, Penn State College of Medicine, Hershey PA, USA
| | - Joshua Cysyk
- Division of Applied Biomedical Engineering, Department of Surgery, Penn State College of Medicine, Hershey PA, USA
| | - William Weiss
- Division of Applied Biomedical Engineering, Department of Surgery, Penn State College of Medicine, Hershey PA, USA.,Department of Biomedical Engineering, Penn State University, University Park, PA, USA
| | - Gerson Rosenberg
- Division of Applied Biomedical Engineering, Department of Surgery, Penn State College of Medicine, Hershey PA, USA.,Department of Biomedical Engineering, Penn State University, University Park, PA, USA
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15
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Dimberg A, Alström U, Ståhle E, Christersson C. Higher Preoperative Plasma Thrombin Potential in Patients Undergoing Surgery for Aortic Stenosis Compared to Surgery for Stable Coronary Artery Disease. Clin Appl Thromb Hemost 2018; 24:1282-1290. [PMID: 29768939 PMCID: PMC6714769 DOI: 10.1177/1076029618776374] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Aortic stenosis (AS) and coronary artery disease (CAD) influence the coagulation system, potentially affecting hemostasis during cardiac surgery. Our aim was to evaluate 2 preoperative global hemostasis assays, plasma thrombin potential and thromboelastometry, in patients with severe aortic valve stenosis compared to patients with CAD. A secondary aim was to test whether the assays were associated with postoperative bleeding. Calibrated automated thrombogram (CAT) in platelet-poor plasma and rotational thromboelastometry (ROTEM) in whole blood were analyzed in patients scheduled for elective surgery due to severe AS (n = 103) and stable CAD (n = 68). Patients with AS displayed higher plasma thrombin potential, both thrombin peak with median 252 nmol/L (interquartile range 187-319) and endogenous thrombin potential (ETP) with median 1552 nmol/L/min (interquartile range 1340-1838), when compared to patients with CAD where thrombin peak was median 174 nmol/L (interquartile range 147-229) and ETP median 1247 nmol/L/min (interquartile range 1034-1448; both P < .001). Differences persisted after adjustment for age, gender, comorbidity, and antithrombotic treatment. Differences observed in thromboelastometry between the groups did not persist after adjustment for baseline characteristics. Bleeding amount showed no relationship with plasma thrombin potential but weakly to thromboelastometry (R2 = .064, P = .001). Patients with AS exhibited preoperatively increased plasma thrombin potential compared to patients with CAD. Plasma thrombin potential was not predictive for postoperative bleeding in patients scheduled for elective surgery.
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Affiliation(s)
- Axel Dimberg
- 1 Section of Thoracic Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Ulrica Alström
- 1 Section of Thoracic Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Elisabeth Ståhle
- 1 Section of Thoracic Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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16
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Oury C, Nchimi A, Lancellotti P, Bergler-Klein J. Can Blood Biomarkers Help Predicting Outcome in Transcatheter Aortic Valve Implantation? Front Cardiovasc Med 2018; 5:31. [PMID: 29644220 PMCID: PMC5882866 DOI: 10.3389/fcvm.2018.00031] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 03/16/2018] [Indexed: 12/14/2022] Open
Abstract
Transcatheter aortic valve implantation (TAVI) has become the method of choice for patients with severe aortic valve stenosis, who are ineligible or at high risk for surgery. In this high risk patient population, early and late mortality and rehospitalization rates after TAVI are still relatively high. In spite of recent improvements in procedural TAVI, and establishment of risk models for poor outcome, determining individual risk remains challenging. In this context, current data from several small studies strongly suggest that blood biomarkers of myocardial injury, cardiac mechanical stretch, inflammation, and hemostasis imbalance might play an important role by providing informations on patient risk at baseline, and postprocedural progression of patient clinical conditions from days up to years post-TAVI. Although the role of biomarkers for predicting survival post-TAVI remains to be validated in large randomized studies, implementing biomarkers in clinical practice might improve risk stratification, thereby further reducing TAVI-associated morbidity and mortality.
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Affiliation(s)
- Cécile Oury
- Department of Cardiology, Heart Valve Clinic, University of Liège Hospital, GIGA Cardiovascular Sciences, CHU Sart Tilman, Liège, Belgium
| | - Alain Nchimi
- Department of Cardiology, Heart Valve Clinic, University of Liège Hospital, GIGA Cardiovascular Sciences, CHU Sart Tilman, Liège, Belgium
| | - Patrizio Lancellotti
- Department of Cardiology, Heart Valve Clinic, University of Liège Hospital, GIGA Cardiovascular Sciences, CHU Sart Tilman, Liège, Belgium.,Gruppo Villa Maria Care and Research, Anthea Hospital, Bari, Italy
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17
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Jalaer I, Tsakiris D, Solecka-Witulska B, Kannicht C. The role of von Willebrand factor in primary haemostasis under conditions of haemodilution. Thromb Res 2017; 157:142-146. [DOI: 10.1016/j.thromres.2017.07.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 06/24/2017] [Accepted: 07/18/2017] [Indexed: 10/19/2022]
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18
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Murphy GJ, Mumford AD, Rogers CA, Wordsworth S, Stokes EA, Verheyden V, Kumar T, Harris J, Clayton G, Ellis L, Plummer Z, Dott W, Serraino F, Wozniak M, Morris T, Nath M, Sterne JA, Angelini GD, Reeves BC. Diagnostic and therapeutic medical devices for safer blood management in cardiac surgery: systematic reviews, observational studies and randomised controlled trials. PROGRAMME GRANTS FOR APPLIED RESEARCH 2017. [DOI: 10.3310/pgfar05170] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BackgroundAnaemia, coagulopathic bleeding and transfusion are strongly associated with organ failure, sepsis and death following cardiac surgery.ObjectiveTo evaluate the clinical effectiveness and cost-effectiveness of medical devices used as diagnostic and therapeutic tools for the management of anaemia and bleeding in cardiac surgery.Methods and resultsWorkstream 1 – in the COagulation and Platelet laboratory Testing in Cardiac surgery (COPTIC) study we demonstrated that risk assessment using baseline clinical factors predicted bleeding with a high degree of accuracy. The results from point-of-care (POC) platelet aggregometry or viscoelastometry tests or an expanded range of laboratory reference tests for coagulopathy did not improve predictive accuracy beyond that achieved with the clinical risk score alone. The routine use of POC tests was not cost-effective. A systematic review concluded that POC-based algorithms are not clinically effective. We developed two new clinical risk prediction scores for transfusion and bleeding that are available as e-calculators. Workstream 2 – in the PAtient-SPecific Oxygen monitoring to Reduce blood Transfusion during heart surgery (PASPORT) trial and a systematic review we demonstrated that personalised near-infrared spectroscopy-based algorithms for the optimisation of tissue oxygenation, or as indicators for red cell transfusion, were neither clinically effective nor cost-effective. Workstream 3 – in the REDWASH trial we failed to demonstrate a reduction in inflammation or organ injury in recipients of mechanically washed red cells compared with standard (unwashed) red cells.LimitationsExisting studies evaluating the predictive accuracy or effectiveness of POC tests of coagulopathy or near-infrared spectroscopy were at high risk of bias. Interventions that alter red cell transfusion exposure, a common surrogate outcome in most trials, were not found to be clinically effective.ConclusionsA systematic assessment of devices in clinical use as blood management adjuncts in cardiac surgery did not demonstrate clinical effectiveness or cost-effectiveness. The contribution of anaemia and coagulopathy to adverse clinical outcomes following cardiac surgery remains poorly understood. Further research to define the pathogenesis of these conditions may lead to more accurate diagnoses, more effective treatments and potentially improved clinical outcomes.Study registrationCurrent Controlled Trials ISRCTN20778544 (COPTIC study) and PROSPERO CRD42016033831 (systematic review) (workstream 1); Current Controlled Trials ISRCTN23557269 (PASPORT trial) and PROSPERO CRD4201502769 (systematic review) (workstream 2); and Current Controlled Trials ISRCTN27076315 (REDWASH trial) (workstream 3).FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 5, No. 17. See the NIHR Journals Library website for further project information.
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Affiliation(s)
- Gavin J Murphy
- Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Leicester, UK
| | - Andrew D Mumford
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
| | - Chris A Rogers
- Clinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, UK
| | - Sarah Wordsworth
- Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Elizabeth A Stokes
- Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Veerle Verheyden
- Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Leicester, UK
| | - Tracy Kumar
- Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Leicester, UK
| | - Jessica Harris
- Clinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, UK
| | - Gemma Clayton
- Clinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, UK
| | - Lucy Ellis
- Clinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, UK
| | - Zoe Plummer
- Clinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, UK
| | - William Dott
- Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Leicester, UK
| | - Filiberto Serraino
- Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Leicester, UK
| | - Marcin Wozniak
- Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Leicester, UK
| | - Tom Morris
- Leicester Clinical Trials Unit, University of Leicester, Leicester, UK
| | - Mintu Nath
- Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Unit in Cardiovascular Medicine, University of Leicester, Leicester, UK
| | - Jonathan A Sterne
- School of Social and Community Medicine, University of Bristol, Bristol, UK
| | - Gianni D Angelini
- Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK
| | - Barnaby C Reeves
- Clinical Trials and Evaluation Unit, School of Clinical Sciences, University of Bristol, Bristol, UK
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19
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Frank RD, Lanzmich R, Haager PK, Budde U. Severe Aortic Valve Stenosis. Clin Appl Thromb Hemost 2016; 23:229-234. [DOI: 10.1177/1076029616660759] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Aortic valve stenosis (AVS) is the most common valve disease in adults. Severe forms are associated with acquired von Willebrand syndrome (aVWS) with loss of the largest von Willebrand factor (VWF) multimers. Diagnostic gold standard is the VWF multimer analysis. Valve replacement rapidly restores the VWF structure. Uncertainty exists if this effect is permanent and how functional VWF assays perform compared with multimer analysis. We studied 21 consecutive patients with severe AVS before and 6 to 18 months after valve surgery and compared them with 14 controls without valve disease referred for coronary angiography. The VWF multimers, VWF antigen (VWF:Ag), VWF collagen binding capacity (VWF:CB), VWF:CB/VWF:Ag ratio, in vitro bleeding time (PFA-100), factor VIII coagulation activity (FVIII:C), and VWF ristocetin cofactor activity (VWF:RCo) were determined. In all patients with AVS, the large VWF multimers were strongly reduced (56 ± 13% of normal plasma); all controls had normal multimers. The PFA-100 collagen/ADP closure times (coll/ADP CT) were prolonged in patients with AVS compared with the controls (175 ± 56 seconds vs 86 ± 14 seconds, P < .001). The VWF:CB/VWF:Ag ratio was pathological in 20 of the 21 patients but normal in controls. After surgery, the multimers normalized in all patients and coll/ADP CT shortened (pre 184 ± 65 seconds vs post 102 ± 22 seconds; P < .001). The VWF:CB/VWF:Ag ratio strongly improved ( P < .001) and normalized in 14 of 17 patients. In conclusion, all consecutive patients with severe AVS had an aVWS. The combination of coll/ADP CT and VWF:CB/VWF:Ag ratio detected the aVWS in all patients. More than 6 months after valve replacement, the VWF multimers were still normalized in all patients indicating a permanent cure of the aVWS.
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Affiliation(s)
- Rolf Dario Frank
- Department of Nephrology and Clinical Immunology, University Hospital, RWTH Aachen, Eschweiler, Germany
| | - Regina Lanzmich
- Department of Nephrology and Clinical Immunology, University Hospital, RWTH Aachen, Eschweiler, Germany
| | - Philipp K. Haager
- Department of Cardiology, Kantonsspital St Gallen, St Gallen, Switzerland
| | - Ulrich Budde
- Medilys Laboratory, Asklepios Klinik Altona, Hamburg, Germany
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20
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Increased bleeding risk in patients with aortic valvular stenosis: From new mechanisms to new therapies. Thromb Res 2016; 139:85-9. [PMID: 26916301 DOI: 10.1016/j.thromres.2016.01.016] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Revised: 01/18/2016] [Accepted: 01/19/2016] [Indexed: 01/21/2023]
Abstract
Aortic stenosis (AS), the most prevalent acquired valvular disease in the adults that requires invasive treatment, coexists with coagulopathy, resulting in bleeding in approximately 20% of patients. In the current review, we summarize the available knowledge on the mechanisms underlying the bleeding tendency observed in AS, and discuss potential compensatory mechanisms preventing most patients with severe AS from experiencing bleeding. We offer an update on Heyde's syndrome and other types of bleeding, and study extensively their pathobiology, providing insights into the new emerging concepts on coagulation regulation in AS. The focus is given to the impact of valvular interventions on coagulation abnormalities in AS. Both surgical valve replacement and transcatheter aortic valve implantation are discussed. Finally, we discuss current treatment recommendations in AS related bleeding.
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21
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Swieringa F, Lancé MD, Fuchs B, Feijge MAH, Solecka BA, Verheijen LPJ, Hughes KR, van Oerle R, Deckmyn H, Kannicht C, Heemskerk JWM, van der Meijden PEJ. Desmopressin treatment improves platelet function under flow in patients with postoperative bleeding. J Thromb Haemost 2015; 13:1503-13. [PMID: 25988848 DOI: 10.1111/jth.13007] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2014] [Accepted: 05/05/2015] [Indexed: 01/31/2023]
Abstract
BACKGROUND Patients undergoing major cardiothoracic surgery are subjected to dilution, owing to massive fluid infusion and blood component transfusion. These patients may experience bleeding perioperatively, and are frequently treated with the endothelium-activating agent desmopressin. OBJECTIVES To investigate the effect of desmopressin administration on von Willebrand factor (VWF)-dependent coagulant and platelet functions under flow conditions. PATIENTS/METHODS Blood from 16 patients with postoperative bleeding was obtained before and after desmopressin treatment (0.3 μg kg(-1) body weight), and assessed for coagulant properties and platelet function. Furthermore, VWF antigen levels and multimer composition were determined in both samples. RESULTS Desmopressin treatment did not change thrombin generation in plasma or whole blood thromboelasticity. Also coagulation factor levels (other than factor VIII) and coagulation times were unchanged, suggesting that desmopressin treatment did not have a major effect on the coagulant activity. On the other hand, desmopressin treatment raised the already high plasma levels of VWF from a median of 116 IU mL(-1) (interquartile range [IQR] 102-154 IU mL(-1) ) to a median of 160 IU mL(-1) (IQR 126-187 IU mL(-1) ) (P = 0.007), owing to accumulation of the high molecular weight VWF multimers. Furthermore, desmopressin treatment caused an increase in collagen-dependent thrombus formation and platelet phosphatidylserine exposure. Markers of thrombus formation correlated with the plasma levels of VWF. In vitro control experiments confirmed a major contribution of VWF to thrombus formation and procoagulant activity under conditions of blood dilution. CONCLUSIONS Desmopressin treatment of patients with bleeding complications after cardiothoracic surgery induces the release of high molecular weight VWF multimers, which enhance platelet activation and thrombus formation under flow conditions.
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Affiliation(s)
- F Swieringa
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
| | - M D Lancé
- Department of Anesthesiology, Maastricht University Medical Center, Maastricht, the Netherlands
| | - B Fuchs
- Department of Molecular Biochemistry Berlin, Octapharma R&D, Berlin, Germany
| | - M A H Feijge
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
| | - B A Solecka
- Department of Molecular Biochemistry Berlin, Octapharma R&D, Berlin, Germany
| | - L P J Verheijen
- Department of Anesthesiology, Diakonessenhuis, Utrecht, the Netherlands
| | - K R Hughes
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
| | - R van Oerle
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
| | - H Deckmyn
- Laboratory for Thrombosis Research, IRF-Life Sciences, KU Leuven Kulak, Kortrijk, Belgium
| | - C Kannicht
- Department of Molecular Biochemistry Berlin, Octapharma R&D, Berlin, Germany
| | - J W M Heemskerk
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
| | - P E J van der Meijden
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
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22
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Abstract
In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation – adhesion, shape change, release reaction, and aggregation – have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT) dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry [MEA]). POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well-tried and innovative platelet function tests and their methodological features and clinical applications are considered.
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Affiliation(s)
- Rita Paniccia
- Department of Experimental and Clinical Medicine, Thrombosis Center, University of Florence, Florence, Italy ; Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | - Raffaella Priora
- Department of Experimental and Clinical Medicine, Thrombosis Center, University of Florence, Florence, Italy ; Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | | | - Rosanna Abbate
- Department of Experimental and Clinical Medicine, Thrombosis Center, University of Florence, Florence, Italy ; Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
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Paniccia R, Priora R, Liotta AA, Maggini N, Abbate R. Assessment of platelet function: Laboratory and point-of-care methods. World J Transl Med 2014; 3:69-83. [DOI: 10.5528/wjtm.v3.i2.69] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2014] [Revised: 03/14/2014] [Accepted: 04/29/2014] [Indexed: 02/05/2023] Open
Abstract
In the event of blood vessel damage, human platelets are promptly recruited on the site of injury and, after their adhesion, activation and aggregation, prevent blood loss with the formation of a clot. The consequence of abnormal regulation can be either hemorrhage or the development of thrombosis. Qualitative and/or quantitative defects in platelets promote bleeding, whereas the residual reactivity of platelets, despite antiplatelet therapies, play an important role in promoting arterial thrombotic complications. Platelet function is traditionally assessed to investigate the origin of a bleeding syndrome, to predict the risk of bleeding prior surgery or during pregnancy or to monitor the efficacy of antiplatelet therapy in thrombotic syndromes that, now, can be considered a new discipline. “Old” platelet function laboratory tests such as the evaluation of bleeding time and the platelet aggregation analysis in platelet-rich plasma are traditionally utilized to aid in the diagnosis and management of patients with platelet and hemostatic disorders and used as diagnostic tools both in bleeding and thrombotic diathesis in specialized laboratories. Now, new and renewed automated systems have been introduced to provide a simple, rapid assessment of platelet function including point of care methods. These new methodologies are also suitable for being used in non-specialized laboratories and in critical area for assessing platelet function in whole blood without the requirement of sample processing. Some of these methods are also beginning to be incorporated into routine clinical use and can be utilized as not only as first panel for the diagnosis of platelet dysfunction, but also for monitoring anti-platelet therapy and to potentially assess risk of both bleeding and/or thrombosis.
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