|
1
|
Rössler J, Li Y, Ott S, Divito A, Sleiman VB, Ruetzler K, Argalious MY. Intrinsic or Nonintrinsic End-stage Liver Disease and Its Association With Thromboelastography-based Coagulation States in Patients Undergoing Liver Transplantation: A Retrospective Cohort Study. J Cardiothorac Vasc Anesth 2024; 38:2368-2376. [PMID: 39129096 DOI: 10.1053/j.jvca.2024.07.036] [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: 05/08/2024] [Revised: 07/17/2024] [Accepted: 07/19/2024] [Indexed: 08/13/2024]
Abstract
OBJECTIVES Perioperative coagulation management in liver transplantation recipients is challenging. Viscoelastic testing with rotational thromboelastography (TEG) can help quantify hemostatic profiles. The current work aimed to investigate whether the etiology of end-stage liver disease, pretransplant disease severity, or pretransplant thrombotic or bleeding complications are associated with specific TEG patterns. DESIGN Retrospective cohort study. SETTING Single quaternary care hospital. PARTICIPANTS A total of 1,078 adult liver transplant patients. INTERVENTIONS The primary exposure was the etiology of end-stage liver disease classified as either intrinsic or nonintrinsic (eg, biliary obstruction or cardiovascular). Secondary exposures were patients' preoperative Model for End-Stage Liver Disease (MELD) score, Child-Pugh class, presence of major preoperative thrombotic complications, and major bleeding complications. MEASUREMENTS AND MAIN RESULTS Patients with intrinsic liver disease (84%) showed higher odds of hypocoagulable (odds ratio [OR]: 3.70, 95% confidence interval [CI]: 1.94-7.07, p < 0.0001) and mixed TEG patterns (OR: 4.59, 95% CI: 2.07-10.16, p = 0.0002) compared with those with nonintrinsic disease. Increasing MELD scores correlated with higher odds of hypocoagulable (OR: 1.14, 95% CI: 1.08-1.19, p < 0.0001) and mixed TEG patterns (OR: 1.08, 95% CI: 1.03-1.14, p = 0.0036). Child-Pugh class C was associated with higher odds of hypocoagulable (OR: 8.55, 95% CI: 3.26-22.42, p < 0.0001) and mixed patterns (OR: 12.48, 95% CI: 3.89-40.03, p < 0.0001). Major preoperative thrombotic complications were not associated with specific TEG patterns, although an interaction with liver disease severity was observed. CONCLUSIONS Liver transplantation candidates with intrinsic liver disease tend to exhibit hypocoagulable TEG patterns, while nonintrinsic disease is associated with hypercoagulability. Increasing end-stage liver disease severity, as evidenced by increasing MELD scores and higher Child-Pugh classification, was also associated with hypocoagulable TEG patterns.
Collapse
Affiliation(s)
- Julian Rössler
- Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH
| | - Yufei Li
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
| | - Sascha Ott
- Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH
| | - Anthony Divito
- Multispecialty Anesthesiology, Anesthesiology Department, Integrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH
| | - Vanessa Bou Sleiman
- Multispecialty Anesthesiology, Anesthesiology Department, Integrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH
| | - Kurt Ruetzler
- Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH; Multispecialty Anesthesiology, Anesthesiology Department, Integrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH
| | - Maged Y Argalious
- Multispecialty Anesthesiology, Anesthesiology Department, Integrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH.
| |
Collapse
|
|
2
|
Lin YL, Yao T, Wang YW, Yu JS, Zhen C, Lin JF, Chen SB. Association between primary biliary cholangitis with diabetes and cardiovascular diseases: A bidirectional multivariable Mendelian randomization study. Clin Res Hepatol Gastroenterol 2024; 48:102419. [PMID: 38992425 DOI: 10.1016/j.clinre.2024.102419] [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: 04/29/2024] [Revised: 07/04/2024] [Accepted: 07/09/2024] [Indexed: 07/13/2024]
Abstract
BACKGROUND AND AIMS Primary biliary cholangitis (PBC) is an autoimmune disease often accompanied by multisystem damage. This study aimed to explore the causal association between genetically predicted PBC and diabetes, as well as multiple cardiovascular diseases (CVDs). METHODS Genome-wide association studies (GWAS) summary data of PBC in 24,510 individuals of European ancestry from the European Association for the Study of the Liver was used to identify genetically predicted PBC. We conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to estimate the impacts of PBC on diabetes (N = 17,685 to 318,014) and 20 CVDs from the genetic consortium (N = 171,875 to 1,030,836). RESULTS SVMR provided evidence that genetically predicted PBC is associated with an increased risk of type 1 diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), heart failure (HF), hypertension, atrial fibrillation (AF), stroke, ischemic stroke, and small-vessel ischemic stroke. Additionally, there was no evidence of a causal association between PBC and coronary atherosclerosis. In the MVMR analysis, PBC maintained independent effects on T1D, HF, MI, and small-vessel ischemic stroke in most models. CONCLUSION Our findings revealed the causal effects of PBC on diabetes and 7 CVDs, and no causal relationship was detected between PBC and coronary atherosclerosis.
Collapse
Affiliation(s)
- Yun-Lu Lin
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
| | - Tao Yao
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
| | - Ying-Wei Wang
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
| | - Jia-Sheng Yu
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
| | - Cheng Zhen
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
| | - Jia-Feng Lin
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China
| | - Shui-Bing Chen
- The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China.
| |
Collapse
|
|
3
|
Di Y, Li J, Ye C, Wang Z, Zhu Q. Thromboelastography parameters in chronic viral liver disease and liver resection: a retrospective study. Singapore Med J 2024; 65:438-443. [PMID: 37077056 PMCID: PMC11382816 DOI: 10.4103/singaporemedj.smj-2021-404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 07/26/2022] [Indexed: 04/21/2023]
Abstract
INTRODUCTION Thromboelastography (TEG) provides a global assessment of haemostasis and is potentially applicable to liver disease. The present study aimed to explore the utility of TEG for the evaluation of patients with chronic viral liver disease, which has previously not been investigated. METHODS Demographic characteristics and TEG parameters were collected before surgery. Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores were used to categorise stages of liver cirrhosis. Liver resections were classified as low, medium and high complexity. RESULTS A total of 344 patients were included. Results showed significantly longer K-time, smaller α-angle and lower maximum amplitude (MA) with increasing liver disease severity as measured by the CTP and MELD scores ( P < 0.05 for all). After multivariable adjustment (including age, sex, liver disease aetiology, alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin, total bilirubin, haemoglobin and platelet count), TEG parameters (except R-times) were either weakly or inversely related to the severity of liver disease as defined by the MELD score (absolute r < 0.2 and P < 0.05 for all except R-times). R-times obtained before surgery were weakly correlated with perioperative blood loss ( r < 0.2 and P < 0.05 for all). CONCLUSIONS The correlation between TEG parameters and severity of liver disease was weak. In addition, R-times obtained before liver resection were weakly associated with perioperative blood loss after multivariable adjustments. TEG utility for haemostasis assessment and prediction of blood loss during liver resection should be further explored in high-quality studies.
Collapse
Affiliation(s)
- Ying Di
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, Shaanxi Province, China
| | - Jialu Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, Shaanxi Province, China
| | - Chunjuan Ye
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, Shaanxi Province, China
| | - Zheng Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an City, Shaanxi Province, China
| | - Qianqian Zhu
- Department of Anesthesiology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen City, People's Republic of China
| |
Collapse
|
|
4
|
Zanetto A, Campello E, Senzolo M, Simioni P. The evolving knowledge on primary hemostasis in patients with cirrhosis: A comprehensive review. Hepatology 2024; 79:460-481. [PMID: 36825598 DOI: 10.1097/hep.0000000000000349] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 02/13/2023] [Indexed: 02/25/2023]
Abstract
Patients with cirrhosis develop complex alterations in primary hemostasis that include both hypocoagulable and hypercoagulable features. This includes thrombocytopenia, multiple alterations of platelet function, and increased plasma levels of von Willebrand factor. Contrary to the historical view that platelet dysfunction in cirrhosis might be responsible for an increased bleeding tendency, the current theory posits a rebalanced hemostasis in patients with cirrhosis. Severe thrombocytopenia is not indicative of the bleeding risk in patients undergoing invasive procedures and does not dictate per se the need for pre-procedural prophylaxis. A more comprehensive and individualized risk assessment should combine hemostatic impairment, the severity of decompensation and systemic inflammation, and the presence of additional factors that may impair platelet function, such as acute kidney injury and bacterial infections. Although there are multiple, complex alterations of platelet function in cirrhosis, their net effect is not yet fully understood. More investigations evaluating the association between alterations of platelet function and bleeding/thrombosis may improve risk stratification in patients with decompensated cirrhosis. Besides hemostasis, the assessment of von Willebrand factor Ag and ADP-induced, whole-blood platelet aggregation normalized by platelet count (VITRO score and PLT ratio) are promising biomarkers to predict the risk of hepatic decompensation and survival in both compensated and decompensated patients. Further investigations into the in vivo interplay between platelets, circulating blood elements, and endothelial cells may help advance our understanding of cirrhotic coagulopathy. Here, we review the complex changes in platelets and primary hemostasis in cirrhosis and their potential clinical implications.
Collapse
Affiliation(s)
- Alberto Zanetto
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università Padova, Padova, Italy
- Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy
| | - Elena Campello
- Department of Medicine, General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Padova University Hospital, Padova, Italy
| | - Marco Senzolo
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università Padova, Padova, Italy
- Department of Surgery, Oncology, and Gastroenterology, University of Padova, Padova, Italy
| | - Paolo Simioni
- Department of Medicine, General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Padova University Hospital, Padova, Italy
| |
Collapse
|
|
5
|
Akbari Aghdam M, Romecín P, García-Estañ J, Atucha NM. Role of Nitric Oxide in the Altered Calcium Homeostasis of Platelets from Rats with Biliary Cirrhosis. Int J Mol Sci 2023; 24:10948. [PMID: 37446122 DOI: 10.3390/ijms241310948] [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: 06/01/2023] [Revised: 06/26/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
INTRODUCTION Previously, we found that intracellular calcium (Ca2+) homeostasis is altered in platelets from an experimental model of liver cirrhosis, namely the bile-duct-ligated (BDL) rat. These alterations are compatible with the existence of a hypercoagulable state. OBJECTIVE In the present study, we analyzed the role of nitric oxide in the abnormal calcium signaling responses of an experimental cirrhosis model, the bile duct-ligated rat. METHODS Chronic treatment with L-NAME was used to inhibit NO production in a group of control and BDL animals, and the responses compared to those obtained in a control and BDL untreated group (n = 6 each). The experiments were conducted on isolated platelets loaded with fura-2, using fluorescence spectrometry. RESULTS Chronic treatment with L-NAME increased thrombin-induced Ca2+ release from internal stores in both control and BDL rats. However, the effect was significantly greater in the BDL rats (p < 0.05). Thrombin-induced calcium entry from the extracellular space was also elevated but at lower doses and, similarly in both control and BDL platelets, treated with the NO synthesis inhibitor. Capacitative calcium entry was also enhanced in the control platelets but not in platelets from BDL rats treated with L-NAME. Total calcium in intracellular stores was elevated in untreated platelets from BDL rats, and L-NAME pretreatment significantly (p < 0.05) elevated these values both in controls and in BDL but significantly more in the BDL rats (p < 0.05). CONCLUSIONS Our results suggest that nitric oxide plays a role in the abnormal calcium signaling responses observed in platelets from BDL rats by interfering with the mechanism that releases calcium from the internal stores.
Collapse
Affiliation(s)
- Masoud Akbari Aghdam
- Departamento de Fisiología, Facultad de Medicina, Instituto Murciano de Investigación Biosanitaria, Universidad de Murcia, 30120 Murcia, Spain
| | - Paola Romecín
- Departamento de Fisiología, Facultad de Medicina, Instituto Murciano de Investigación Biosanitaria, Universidad de Murcia, 30120 Murcia, Spain
| | - Joaquín García-Estañ
- Departamento de Fisiología, Facultad de Medicina, Instituto Murciano de Investigación Biosanitaria, Universidad de Murcia, 30120 Murcia, Spain
| | - Noemí M Atucha
- Departamento de Fisiología, Facultad de Medicina, Instituto Murciano de Investigación Biosanitaria, Universidad de Murcia, 30120 Murcia, Spain
| |
Collapse
|
|
6
|
Pérez-Calatayud AA, Hofmann A, Pérez-Ferrer A, Escorza-Molina C, Torres-Pérez B, Zaccarias-Ezzat JR, Sanchez-Cedillo A, Manuel Paez-Zayas V, Carrillo-Esper R, Görlinger K. Patient Blood Management in Liver Transplant—A Concise Review. Biomedicines 2023; 11:biomedicines11041093. [PMID: 37189710 DOI: 10.3390/biomedicines11041093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 03/09/2023] [Accepted: 03/13/2023] [Indexed: 04/07/2023] Open
Abstract
Transfusion of blood products in orthotopic liver transplantation (OLT) significantly increases post-transplant morbidity and mortality and is associated with reduced graft survival. Based on these results, an active effort to prevent and minimize blood transfusion is required. Patient blood management is a revolutionary approach defined as a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient’s own blood while promoting patient safety and empowerment. This approach is based on three pillars of treatment: (1) detecting and correcting anemia and thrombocytopenia, (2) minimizing iatrogenic blood loss, detecting, and correcting coagulopathy, and (3) harnessing and increasing anemia tolerance. This review emphasizes the importance of the three-pillar nine-field matrix of patient blood management to improve patient outcomes in liver transplant recipients.
Collapse
Affiliation(s)
| | - Axel Hofmann
- Faculty of Health and Medical Sciences, Discipline of Surgery, The University of Western Australia, Perth 6907, WA, Australia
- Institute of Anesthesiology, University of Zurich and University Hospital Zurich, 8057 Zurich, Switzerland
| | - Antonio Pérez-Ferrer
- Department of Anesthesiology, Infanta Sofia University Hospital, 28700 San Sebastián de los Reyes, Spain
- Department of Anesthesiology, European University of Madrid, 28702 Madrid, Spain
| | - Carla Escorza-Molina
- Departmen of Anesthesiology, Hospital General de México Dr. Eduardo Liceaga, Mexico City 06720, Mexico
| | - Bettina Torres-Pérez
- Department of Anesthesiology, Pediatric Transplant, Centro Medico de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44329, Mexico
| | | | - Aczel Sanchez-Cedillo
- Transplant Department Hospital General de México Dr. Eduardo Liceaga, Mexico City 06720, Mexico
| | - Victor Manuel Paez-Zayas
- Gastroenterology Department Hospital General de México Dr. Eduardo Liceaga, Mexico City 06720, Mexico
| | | | - Klaus Görlinger
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, 45131 Essen, Germany
- TEM Innovations GmbH, 81829 Munich, Germany
| |
Collapse
|
|
7
|
Stewart E, Nydam TL, Hendrickse A, Pomposelli JJ, Pomfret EA, Moore HB. Viscoelastic Management of Coagulopathy during the Perioperative Period of Liver Transplantation. Semin Thromb Hemost 2023; 49:119-133. [PMID: 36318962 PMCID: PMC10366939 DOI: 10.1055/s-0042-1758058] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Viscoelastic testing (VET) in liver transplantation (LT) has been used since its origin, in combination with standard laboratory testing (SLT). There are only a few, small, randomized controlled trials that demonstrated a reduction in transfusion rates using VET to guide coagulation management. Retrospective analyses contrasting VET to SLT have demonstrated mixed results, with a recent concern for overtreatment and the increase in postoperative thrombotic events. An oversight of many studies evaluating VET in LT is a single protocol that does not address the different phases of surgery, in addition to pre- and postoperative management. Furthermore, the coagulation spectrum of patients entering and exiting the operating room is diverse, as these patients can have varying anatomic and physiologic risk factors for thrombosis. A single transfusion strategy for all is short sighted. VET in combination with SLT creates the opportunity for personalized resuscitation in surgery which can address the many challenges in LT where patients are at a paradoxical risk for both life-threatening bleeding and clotting. With emerging data on the role of rebalanced coagulation in cirrhosis and hypercoagulability following LT, there are numerous potential roles in VET management of LT that have been unaddressed.
Collapse
Affiliation(s)
- Erin Stewart
- Department of Anesthesia, University of Colorado School of Medicine, Aurora, Colorado
| | - Trevor L. Nydam
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Adrian Hendrickse
- Department of Anesthesia, University of Colorado School of Medicine, Aurora, Colorado
| | - James J. Pomposelli
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Elizabeth A. Pomfret
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| | - Hunter B. Moore
- Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado
| |
Collapse
|
|
8
|
Rogalski P, Bogdanowska-Charkiewicz D, Rogalska-Plonska M, Lukaszewicz-Zajac M, Kostecka-Roslen I, Mroczko B, Dabrowska M, Wasielica-Berger J, Aleksiejuk E, Antonowicz S, Dabrowski A, Daniluk J, Janica J. Elevated levels of soluble glycoprotein V - The plasma marker of platelet activation by thrombin in patients with early stage primary biliary cholangitis (PBC). Adv Med Sci 2023; 68:71-78. [PMID: 36758500 DOI: 10.1016/j.advms.2023.01.002] [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: 07/14/2022] [Revised: 10/30/2022] [Accepted: 01/19/2023] [Indexed: 02/09/2023]
Abstract
PURPOSE There is a growing body of evidence for a prothrombotic tendency in patients with primary biliary cholangitis (PBC). The aim of the study was to evaluate coagulation disorders in patients with early stage PBC compared to healthy controls and evaluation of their relationship with clinical data, with particular emphasis on minimal hepatic encephalopathy (MHE). PATIENTS AND METHODS Fifty-one participants (PBC group - 38 patients, all patients but one Child-Pugh A; control group - 13 healthy controls) were included in our prospective, single center study. We assessed the plasma levels of sGPV, plasma procoagulant phospholipids (PPL) and rotational thromboelastometry (ROTEM) profiles in all study participants. Porto-systemic encephalopathy syndrome test was used to assess MHE. RESULTS The sGPV levels were higher in the PBC group compared to the controls: 36.07 ± 11.32 ng/mL vs 27.04 ± 11.72 ng/mL, p = 0.031. The PPL level was lower in the PBC group compared to controls resulting in increased clotting time in a factor Xa-based coagulation assay: 54.65 (47.83-58.83) sec. vs 45.90 (43.3-50.5) sec., p = 0.0065. PPL levels were correlated with platelet count (rho = -0.46, p = 0.001). ROTEM parameters did not differ significantly between groups. Coagulation parameters did not differ significantly between patients with and without MHE. CONCLUSIONS We have showed increased levels of sGPV - a plasma marker of platelet activation by thrombin in patients with early stage PBC compared to healthy controls. We found no relationship between the coagulation disorders and the occurrence of MHE. The PPL level was lower in the PBC group.
Collapse
Affiliation(s)
- Pawel Rogalski
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
| | | | | | | | - Ines Kostecka-Roslen
- Department of Haematological Diagnostics, Medical University of Bialystok, Bialystok, Poland
| | - Barbara Mroczko
- Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok, Poland
| | - Milena Dabrowska
- Department of Haematological Diagnostics, Medical University of Bialystok, Bialystok, Poland
| | - Justyna Wasielica-Berger
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Elzbieta Aleksiejuk
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Stefania Antonowicz
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Andrzej Dabrowski
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Jaroslaw Daniluk
- Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Jacek Janica
- Department of Radiology, Medical University of Bialystok, Bialystok, Poland; Department of Paediatric Radiology, Medical University of Bialystok, Bialystok, Poland
| |
Collapse
|
|
9
|
Tomić Mahečić T, Baronica R, Mrzljak A, Boban A, Hanžek I, Karmelić D, Babić A, Mihaljević S, Meier J. Individualized Management of Coagulopathy in Patients with End-Stage Liver Disease. Diagnostics (Basel) 2022; 12:diagnostics12123172. [PMID: 36553179 PMCID: PMC9777026 DOI: 10.3390/diagnostics12123172] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/02/2022] [Accepted: 12/14/2022] [Indexed: 12/23/2022] Open
Abstract
Over the last decades, individualized approaches and a better understanding of coagulopathy complexity in end-stage liver disease (ESLD) patients has evolved. The risk of both thrombosis and bleeding during minimally invasive interventions or surgery is associated with a worse outcome in this patient population. Despite deranged quantitative and qualitative coagulation laboratory parameters, prophylactic coagulation management is unnecessary for patients who do not bleed. Transfusion of red blood cells (RBCs) and blood products carries independent risks for morbidity and mortality, including modulation of the immune system with increased risk for nosocomial infections. Optimal coagulation management in these complex patients should be based on the analysis of standard coagulation tests (SCTs) and viscoelastic tests (VETs). VETs represent an individualized approach to patients and can provide information about coagulation dynamics in a concise period of time. This narrative review will deliver the pathophysiology of deranged hemostasis in ESLD, explore the difficulties of evaluating the coagulopathies in liver disease patients, and examine the use of VET assays and management of coagulopathy using coagulation factors. Methods: A selective literature search with PubMed as the central database was performed with the following.
Collapse
Affiliation(s)
- Tina Tomić Mahečić
- Clinic of Anesthesiology, Reanimatology and Intensive Care Medicine, and Pain Treatment, University Hospital Center Zagreb, 10000 Zagreb, Croatia
- Correspondence: ; Tel.: +385-98-457-189
| | - Robert Baronica
- Clinic of Anesthesiology, Reanimatology and Intensive Care Medicine, and Pain Treatment, University Hospital Center Zagreb, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
- Liver Transplant Center, Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Ana Boban
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
- Department of Hematology, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Ivona Hanžek
- Clinic of Anesthesiology, Reanimatology and Intensive Care Medicine, and Pain Treatment, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Dora Karmelić
- Clinic of Anesthesiology, Reanimatology and Intensive Care Medicine, and Pain Treatment, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Anđela Babić
- Clinic of Anesthesiology, Reanimatology and Intensive Care Medicine, and Pain Treatment, University Hospital Center Zagreb, 10000 Zagreb, Croatia
| | - Slobodan Mihaljević
- Clinic of Anesthesiology, Reanimatology and Intensive Care Medicine, and Pain Treatment, University Hospital Center Zagreb, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Jens Meier
- Clinic of Anesthesiology and Intensive Care Medicine, Kepler University Clinic, Johannes Kepler University, 4040 Linz, Austria
| |
Collapse
|
|
10
|
Garg P, Harrison B, Gane EJ. Incident portal vein thrombosis in liver transplant recipients in New Zealand: Predictors of risk and validation of portal vein thrombosis risk index calculator. FRONTIERS IN TRANSPLANTATION 2022; 1:1042684. [PMID: 38994395 PMCID: PMC11235241 DOI: 10.3389/frtra.2022.1042684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 10/20/2022] [Indexed: 07/13/2024]
Abstract
The risk of spontaneous portal vein thrombosis (PVT) is increased in patients on the waiting list for liver transplantation and increases perioperative risks. A predictive PVT risk-index (PVT-RI) calculator has been proposed to determine the risk of incident PVT. We performed a retrospective analysis on adult liver transplant recipients at the NZ Liver Transplant Unit between January 1998 and February 2020. Variables reviewed included age at listing and transplantation, wait time from listing to transplant, indication for listing, gender, ethnicity, etiology of liver disease, listing MELD score, hepatocellular carcinoma (HCC), moderate-to-severe ascites, hepatic encephalopathy (>grade 2), transjugular intrahepatic portosystemic shunt (TIPSS), spontaneous bacterial peritonitis (SBP), and diabetes. Incident PVT was determined by imaging of patients while on the waiting list and assessment at transplantation. A total of 553 out of 706 patients met the inclusion criteria. Of those 553, 18 (3.3%) patients had incident PVT. The PVT-RI calculator was not validated in our cohort with only one of those 18 (6%) patients having a score of >4.6 (high risk cut-off score). Longer waiting time for transplant and listing for liver failure rather than HCC were independent predictors of the risk of incident PVT. There was no statistically significant difference in the incidence of PVT in viral vs. non-viral and cholestatic vs. non-cholestatic etiology of chronic liver disease. Patients with longer waiting times on the transplant waiting list should be monitored regularly for PVT.
Collapse
Affiliation(s)
- Paras Garg
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - Barry Harrison
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - Edward J Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
- Faculty of Medicine, University of Auckland, Auckland, New Zealand
| |
Collapse
|
|
11
|
Takeuchi M, Onoda M, Iwamura M, Inokuchi T, Kawano K, Katoh T, Furutani A. A Case of Preserved Blood Flow to the Portal Vein Due to the Concurrent Reconstruction of the Superior Mesenteric Vein and the Splenic Vein Using an Artificial Blood Vessel. Cureus 2022; 14:e31457. [DOI: 10.7759/cureus.31457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/13/2022] [Indexed: 11/15/2022] Open
|
|
12
|
He Y, Yao H, Ageno W, Méndez-Sánchez N, Guo X, Qi X. Review article: thromboelastography in liver diseases. Aliment Pharmacol Ther 2022; 56:580-591. [PMID: 35698893 DOI: 10.1111/apt.17080] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 05/16/2022] [Accepted: 05/29/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Patients with liver diseases have complicated haemostatic alternations, resulting in both bleeding and thromboembolic complications, which cannot be sufficiently evaluated by conventional coagulation tests (CCTs), such as platelet count or prothrombin time. Thromboelastography (TEG) is a whole blood viscoelastic test which globally reflects changes in the haemostatic system, and its utility in evaluating patients with liver disease is increasingly recognised. AIMS To review the current evidence and clinical significance of TEG in liver diseases. METHODS Literature regarding TEG and liver diseases was comprehensively searched. RESULTS TEG is associated closely with the severity and aetiology of liver disease, the course of infection and the risk of bleeding and death, but not the risk of portal venous system thrombosis. Additionally, TEG-guided transfusion protocols can significantly decrease the requirement for blood products compared to those guided by CCTs. CONCLUSION TEG can reflect the haemostatic status of liver diseases more comprehensively than CCTs. It has the potential to assess the severity of liver diseases, predict the risk of bleeding and death in patients with liver disease and guide blood product transfusion. Future studies should standardise the use of TEG for assessing disease severity and development of clinical events and guiding blood product transfusion in patients with liver diseases.
Collapse
Affiliation(s)
- Yanglan He
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China.,Postgraduate College, China Medical University, Shenyang, China
| | - Haijuan Yao
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Walter Ageno
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Nahum Méndez-Sánchez
- Liver Research Unit Medica Sur Clinic & Foundation and Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | - Xiaozhong Guo
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| |
Collapse
|
|
13
|
Validation of 5 models predicting transfusion, bleeding, and mortality in liver transplantation: an observational cohort study. HPB (Oxford) 2022; 24:1305-1315. [PMID: 35131142 DOI: 10.1016/j.hpb.2022.01.002] [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: 05/25/2021] [Revised: 12/08/2021] [Accepted: 01/03/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Historically, orthotopic liver transplantation (OLT) has been associated with massive blood loss, blood transfusion and morbidity. In order to predict such outcomes five nomograms have been published relating to transfusions and morbidity associated with OLTs. These nomograms, developed on the basis of three cohorts of patients consisting of 406, 750, and 800 having undergone OLTs, aimed to predict a transfusion of ≥1 red blood cell unit (RBC), a transfusion of >2 RBC units, a blood loss of >900 ml, as well as one-month and one-year survival rates. The aim of this study was to validate these five nomograms in a contemporary, independent cohort of patients. METHODS Five nomograms were previously developed based on 406, 750, and 800 OLTs. In this study we performed a temporal validation of these nomograms on contemporary patients that consisted of three cohorts of 800, 250, and 200 OLTs. Logistic regression coefficients from the historic development cohorts were applied to the three contemporary temporal validation cohorts. RESULTS The most accurate nomogram was able to predict transfusion of ≥1 RBC units with an area under the curve (AUC) was 0.91. The second-best nomogram was able to predict bleeding of >900 ml with an AUC of 0.70. T he AUC of the third nomogram (transfusion of >2 RBC units) was 0.70. However, is temporal validation was suboptimal, due to a low prevalence of OLTs transfused with >2 RBC units. The last 2 nomograms exhibited clearly suboptimal AUC values of 0.54 and 0.61. CONCLUSION Two of the five nomograms predict blood transfusion and blood loss with excellent accuracy. Transfusion of ≥1 RBC unit and blood loss of >900 ml can be predicted on the basis of these nomograms. However, these nomograms are not accurate to predict one-month and one-year survival rates. These results should be further cross-validated, ideally prospectively, in additional external independent cohorts.
Collapse
|
|
14
|
Pavlick M, DeLaforcade A, Penninck DG, Webster CRL. Evaluation of coagulation parameters in dogs with gallbladder mucoceles. J Vet Intern Med 2021; 35:1763-1772. [PMID: 34196054 PMCID: PMC8295708 DOI: 10.1111/jvim.16203] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 06/05/2021] [Accepted: 06/15/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Gallbladder mucocele (GBM) is a common biliary disorder in dogs. Limited information is available on the coagulation status of dogs with GBM. HYPOTHESIS/OBJECTIVES To determine patterns of coagulation alterations in dogs with GBM and correlate them with clinicopathologic abnormalities and ultrasonographic findings of disease severity. ANIMALS Twenty-three dogs with GBM identified on ultrasound examination were prospectively enrolled. METHODS At the time of GBM identification, blood and urine were collected for CBC, serum biochemical panel, urinalysis, prothrombin time, activated partial thromboplastin time (aPTT), factor VIII, protein C (PC), von Willebrand's factor (vWF), antithrombin activity, fibrinogen, D-dimers, and thromboelastrography (TEG). Gallbladder mucoceles were classified into ultrasound types 1 to 5. Medical records were reviewed for clinical presentation, underlying conditions and to determine if systemic inflammatory response syndrome (SIRS) was present. RESULTS Based on TEG parameters, maximal amplitude, and G, 19/23 (83%) of dogs with GBM had evaluations consistent with hypercoagulability. On plasma-based coagulation testing, dogs with GBM had increased total PC activity (20/23, 87%), fibrinogen (9/23, 39%), platelet count (9/23, 39%), and D-dimers (6/15, 40%) as well as prolongations in aPTT (9/22, 41%) and low vWF activity (5/21, 24%). No correlation was found between TEG G value and any coagulation or clinical pathology variables, ultrasound stage of GBM or disease severity as assessed by the presence of SIRS. CONCLUSIONS AND CLINICAL IMPORTANCE Dogs with ultrasonographically identified GBM have changes in whole blood kaolin-activated TEG supporting a hypercoagulable state although traditional plasma-based coagulation testing suggests that a complex state of hemostasis exists.
Collapse
Affiliation(s)
- Michelle Pavlick
- Cummings School of Veterinary Medicine at Tufts University, Grafton, Massachusetts, USA
| | - Armelle DeLaforcade
- Cummings School of Veterinary Medicine at Tufts University, Grafton, Massachusetts, USA
| | - Dominique G Penninck
- Cummings School of Veterinary Medicine at Tufts University, Grafton, Massachusetts, USA
| | - Cynthia R L Webster
- Cummings School of Veterinary Medicine at Tufts University, Grafton, Massachusetts, USA
| |
Collapse
|
|
15
|
Buliarca A, Horhat A, Mocan T, Craciun R, Procopet B, Sparchez Z. Viscoelastic tests in liver disease: where do we stand now? World J Gastroenterol 2021; 27:3290-3302. [PMID: 34163112 PMCID: PMC8218367 DOI: 10.3748/wjg.v27.i23.3290] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 03/17/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Hemostasis is a complex physiological process based on the balance between pro-coagulant and anticoagulant systems to avoid pathological bleeding or thrombosis. The changes in standard coagulation tests in liver disease were assumed to reflect an acquired bleeding disorder, and cirrhotic patients were considered naturally anticoagulated. In the light of the new evidence, the theory of rebalanced hemostasis replaced the old concept. According to this model, the hemostatic alteration leads to a unique balance between pro-coagulant, anticoagulant, and fibrinolytic systems. But the balance is fragile and may prone to bleeding or thrombosis depending on various risk factors. The standard coagulation tests [INR (international normalized ratio), platelet count and fibrinogen] only explore parts of the hemostasis, not offering an entire image of the process. Rotational thromboelastometry (ROTEM) and thromboelastography (TEG) are both point of care viscoelastic tests (VET) that provide real-time and dynamic information about the entire hemostasis process, including clot initiation (thrombin generation), clot kinetics, clot strength, and clot stability (lysis). Despite prolonged PT/INR (international normalized ratio of prothrombin time) and low platelet counts, VET is within the normal range in many patients with both acute and chronic liver disease. However, bleeding remains the dominant clinical issue in patients with liver diseases, especially when invasive interventions are required. VET has been shown to asses more appropriately the risk of bleeding than conventional laboratory tests, leading to decrial use of blood products transfusion. Inappropriate clotting is common but often subtle and may be challenging to predict even with the help of VET. Although VET has shown its benefit, more studies are needed to establish cut-off values for TEG and ROTEM in these populations and standardization of transfusion guidelines before invasive interventions in cirrhotic patients/orthotopic liver transplantation.
Collapse
Affiliation(s)
- Alina Buliarca
- The Third Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca 400162, Romania
| | - Adelina Horhat
- The Third Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca 400162, Romania
| | - Tudor Mocan
- The Third Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca 400162, Romania
| | - Rares Craciun
- The Third Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca 400162, Romania
| | - Bogdan Procopet
- The Third Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca 400162, Romania
| | - Zeno Sparchez
- The Third Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and Hepatology “Prof. Dr. O. Fodor”, Cluj-Napoca 400162, Romania
| |
Collapse
|
|
16
|
Rangaswamy C, Mailer RK, Englert H, Konrath S, Renné T. The contact system in liver injury. Semin Immunopathol 2021; 43:507-517. [PMID: 34125270 PMCID: PMC8202222 DOI: 10.1007/s00281-021-00876-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 05/27/2021] [Indexed: 01/18/2023]
Abstract
Coagulation is controlled by a delicate balance of prothrombotic and antithrombotic mechanisms, to prevent both excessive blood loss from injured vessels and pathologic thrombosis. The liver plays a pivotal role in hemostasis through the synthesis of plasma coagulation factors and their inhibitors that, in addition to thrombosis and hemostasis, orchestrates an array of inflammatory responses. As a result, impaired liver function has been linked with both hypercoagulability and bleeding disorders due to a pathologic balance of pro- and anticoagulant plasma factors. At sites of vascular injury, thrombus propagation that finally may occlude the blood vessel depends on negatively charged biopolymers, such as polyphosphates and extracellular DNA, that provide a physiological surface for contact activation of coagulation factor XII (FXII). FXII initiates the contact system that drives both the intrinsic pathway of coagulation, and formation of the inflammatory mediator bradykinin by the kallikrein–kinin system. Moreover, FXII facilitates receptor-mediated signalling, thereby promoting mitogenic activities, angiogenesis, and neutrophil stimulation with implications for liver diseases. Here, we summarize current knowledge on the FXII-driven contact system in liver diseases and review therapeutic approaches to target its activities during impaired liver function.
Collapse
Affiliation(s)
- Chandini Rangaswamy
- Institute of Clinical Chemistry and Laboratory Medicine (O26), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany
| | - Reiner K Mailer
- Institute of Clinical Chemistry and Laboratory Medicine (O26), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany
| | - Hanna Englert
- Institute of Clinical Chemistry and Laboratory Medicine (O26), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany
| | - Sandra Konrath
- Institute of Clinical Chemistry and Laboratory Medicine (O26), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany
| | - Thomas Renné
- Institute of Clinical Chemistry and Laboratory Medicine (O26), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany.
| |
Collapse
|
|
17
|
Thrombocytopenia and Hemostatic Changes in Acute and Chronic Liver Disease: Pathophysiology, Clinical and Laboratory Features, and Management. J Clin Med 2021; 10:jcm10071530. [PMID: 33917431 PMCID: PMC8038677 DOI: 10.3390/jcm10071530] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 03/22/2021] [Accepted: 03/24/2021] [Indexed: 12/12/2022] Open
Abstract
Thrombocytopenia, defined as a platelet count <150,000/μL, is the most common complication of advanced liver disease or cirrhosis with an incidence of up to 75%. A decrease in platelet count can be the first presenting sign and tends to be proportionally related to the severity of hepatic failure. The pathophysiology of thrombocytopenia in liver disease is multifactorial, including (i) splenomegaly and subsequently increased splenic sequestration of circulating platelets, (ii) reduced hepatic synthesis of thrombopoietin with missing stimulation both of megakaryocytopoiesis and thrombocytopoiesis, resulting in diminished platelet production and release from the bone marrow, and (iii) increased platelet destruction or consumption. Among these pathologies, the decrease in thrombopoietin synthesis has been identified as a central mechanism. Two newly licensed oral thrombopoietin mimetics/receptor agonists, avatrombopag and lusutrombopag, are now available for targeted treatment of thrombocytopenia in patients with advanced liver disease, who are undergoing invasive procedures. This review summarizes recent advances in the understanding of defective but at low level rebalanced hemostasis in stable cirrhosis, discusses clinical consequences and persistent controversial issues related to the inherent bleeding risk, and is focused on a risk-adapted management of thrombocytopenia in patients with chronic liver disease, including a restrictive transfusion regimen.
Collapse
|
|
18
|
Vlachogiannakos J, Binas J, Siakavellas S, Karagiannakis DS, Voulgaris T, Papatheodoridis GV, Ladas SD. Platelet activation and hypercoagulability in patients with early primary biliary cholangitis compared with healthy controls. Ann Gastroenterol 2021; 34:229-234. [PMID: 33654364 PMCID: PMC7903578 DOI: 10.20524/aog.2021.0572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 09/23/2020] [Indexed: 11/23/2022] Open
Abstract
Background Patients with primary biliary cholangitis (PBC) who have advanced disease are hypercoagulable, with no thrombophilic factors compared to non-cholestatic cirrhotics. We investigated whether hypercoagulability is present in early-stage PBC. Methods PBC patients with biopsy-documented early disease and healthy controls matched by sex and age were asked to participate in the study. All were evaluated using rotational thromboelastometry (ROTEM), platelet aggregation, and flow cytometry. Four ROTEM parameters were evaluated (clotting time, clotting formation time, α-angle, and maximum clot firmness [MCF]). Platelet aggregation was determined as the maximal change in light transmission after the addition of adenosine diphosphate, collagen and epinephrine. Flow cytometry was used to evaluate the expression of glycoprotein (GP) IIb, GPIIa, and P-selectin on the platelet surface. Results We enrolled 50 individuals in the study (25 PBC patients, 25 controls). Prothrombin time and activated partial thromboplastin time did not differ significantly between PBC patients and controls (P-value not significant). In ROTEM, aaaaaaaa-angle and MCF parameters were abnormally elevated in 9 (36%) PBC patients compared to 3 (12%) healthy controls and the difference was statistically significant (P=0.026). Platelet aggregation in PBC patients was not significantly different from controls. In flow cytometry, GPIIb and P-selectin expression was greater in PBC patients than in the control group and the difference was statistically significant (P=0.005 and P=0.006 respectively). Conclusion In this study, we used a combination of sophisticated methods to detect evidence of platelet activation and hypercoagulability in patients with early PBC. Our findings may have important clinical implications and merit further investigation.
Collapse
Affiliation(s)
- Jiannis Vlachogiannakos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, "Laiko" General Hospital, Athens, Greece (Jiannis Vlachogiannakos, Jiannis Binas, Spyros Siakavellas, Dimitrios S. Karagiannakis, Theodoros Voulgaris, George V. Papatheodoridis, Spiros D. Ladas)
| | - Jiannis Binas
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, "Laiko" General Hospital, Athens, Greece (Jiannis Vlachogiannakos, Jiannis Binas, Spyros Siakavellas, Dimitrios S. Karagiannakis, Theodoros Voulgaris, George V. Papatheodoridis, Spiros D. Ladas)
| | - Spyros Siakavellas
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, "Laiko" General Hospital, Athens, Greece (Jiannis Vlachogiannakos, Jiannis Binas, Spyros Siakavellas, Dimitrios S. Karagiannakis, Theodoros Voulgaris, George V. Papatheodoridis, Spiros D. Ladas)
| | - Dimitrios S Karagiannakis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, "Laiko" General Hospital, Athens, Greece (Jiannis Vlachogiannakos, Jiannis Binas, Spyros Siakavellas, Dimitrios S. Karagiannakis, Theodoros Voulgaris, George V. Papatheodoridis, Spiros D. Ladas)
| | - Theodoros Voulgaris
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, "Laiko" General Hospital, Athens, Greece (Jiannis Vlachogiannakos, Jiannis Binas, Spyros Siakavellas, Dimitrios S. Karagiannakis, Theodoros Voulgaris, George V. Papatheodoridis, Spiros D. Ladas)
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, "Laiko" General Hospital, Athens, Greece (Jiannis Vlachogiannakos, Jiannis Binas, Spyros Siakavellas, Dimitrios S. Karagiannakis, Theodoros Voulgaris, George V. Papatheodoridis, Spiros D. Ladas)
| | - Spiros D Ladas
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, "Laiko" General Hospital, Athens, Greece (Jiannis Vlachogiannakos, Jiannis Binas, Spyros Siakavellas, Dimitrios S. Karagiannakis, Theodoros Voulgaris, George V. Papatheodoridis, Spiros D. Ladas)
| |
Collapse
|
|
19
|
Kakar N, Daniel G, Fellman C, de Laforcade A, Webster CRL. Thromboelastography in cats with cholestatic liver disease. J Feline Med Surg 2021; 23:160-167. [PMID: 32672497 PMCID: PMC10741348 DOI: 10.1177/1098612x20939828] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES While thromboelastography (TEG) has helped define a complex state of hemostasis in dogs and humans with hepatobiliary disease, it has not been explored in cats with cholestatic liver disease (CLD). The objective of this study was to describe TEG parameters in cats with CLD and to compare these parameters with conventional plasma-based coagulation tests, white blood cell (WBC) count and biochemical indicators of liver disease grade and severity. METHODS Eighteen cats with CLD, defined by a serum bilirubin ⩾3 mg/dl and a greater than two-fold increase in serum alanine aminotransferase (ALT) and/or alkaline phosphatase (ALP) activity, were prospectively enrolled. All cats received vitamin K1 subcutaneously for 24-36 h prior to acquisition of blood for kaolin-activated TEG analysis, prothrombin time (PT) and activated partial thromboplastin time (aPTT). Patient total solids, packed cell volume, platelet count, WBC count, and serum liver enzymes and bilirubin were extracted from the medical record and correlated with coagulation test results. RESULTS TEG global clot strength (TEG G) values defined 9/18 (50%), 5/18 (28%) and 4/18 (22%) cats as hypercoagulable, normocoagulable or hypocoagulable, respectively. TEG G was significantly negatively correlated with PT, aPTT and serum ALP activity and positively correlated with total solids. Five cats (5/18, 28%) were hyperfibrinolytic with clot lysis at 60 mins (LY 60) >15.3%. LY 60 was significantly positively correlated with PT. CONCLUSIONS AND RELEVANCE By TEG analysis, cholestatic cats replete with vitamin K1 display a variety of coagulation profiles. Indications of synthetic failure (prolonged PT and aPTT) were associated with hypocoagulable and hyperfibrinolytic TEG parameters. High disease activity (serum ALP) was associated with a hypocoagulable state.
Collapse
Affiliation(s)
- Neketa Kakar
- Small Animal Internal Medicine, Cummings
School of Veterinary Medicine at Tufts University, Grafton, MA, USA
| | - Gideon Daniel
- Friendship Hospital for Small Animals,
Washington, DC, USA
| | - Claire Fellman
- Department of Clinical Sciences,
Cummings School of Veterinary Medicine at Tufts University, Grafton, MA, USA
| | - Armelle de Laforcade
- Department of Clinical Sciences,
Cummings School of Veterinary Medicine at Tufts University, Grafton, MA, USA
| | - Cynthia RL Webster
- Department of Clinical Sciences,
Cummings School of Veterinary Medicine at Tufts University, Grafton, MA, USA
| |
Collapse
|
|
20
|
Janko N, Majeed A, Kemp W, Roberts SK. Viscoelastic Tests as Point-of-Care Tests in the Assessment and Management of Bleeding and Thrombosis in Liver Disease. Semin Thromb Hemost 2020; 46:704-715. [PMID: 32932542 DOI: 10.1055/s-0040-1715475] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Viscoelastic point-of-care (VET POC) tests provide a global assessment of hemostasis and have an increasing role in the management of bleeding and blood component delivery across several clinical settings. VET POC tests have a rapid turnaround time, provide a better overall picture of hemostasis, predict bleeding more accurately than conventional coagulation tests, and reduce blood component usage and health care costs. Despite commonly having abnormal conventional coagulation tests, most patients with chronic liver disease have a "rebalanced" hemostasis. However, this hemostatic balance is delicate and these patients are predisposed to both bleeding and thromboembolic events. Over recent years, VET POC tests have been increasingly studied for their potential as better functional tests of hemostasis in liver disease patients. This review provides a background on the most common VET POC tests (thromboelastography and rotational thromboelastometry) and discusses the current evidence for these tests in the prediction and management of bleeding and thrombosis in patients with chronic liver disease, and in liver resection and transplant. With the recent publication of several randomized controlled trials, there is growing evidence that VET POC tests may be used to improve bleeding risk assessment and reduce blood product use in liver disease patients outside of the transplant setting. However, consensus is still lacking regarding the VET POC tests' thresholds that should be used to trigger blood product transfusion. VET POC tests also show promise in predicting thrombosis in patients with liver disease, but further research is needed before they can be used to guide anticoagulant therapy.
Collapse
Affiliation(s)
- Natasha Janko
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia.,Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Ammar Majeed
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia.,Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - William Kemp
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia.,Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Stuart K Roberts
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia.,Central Clinical School, Monash University, Melbourne, Victoria, Australia
| |
Collapse
|
|
21
|
Portal vein thrombosis prevalence and mortality among alcoholic cirrhosis in a nationwide inpatient cohort. Eur J Gastroenterol Hepatol 2020; 32:1160-1167. [PMID: 31834054 DOI: 10.1097/meg.0000000000001624] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Portal vein thrombosis is commonly associated with cirrhosis. The effect of alcoholic cirrhosis on portal vein thrombosis prevalence and mortality has not been well studied. METHODS We conducted a retrospective cohort study utilizing the 2000-2014 National Inpatient Sample Database. We included patients older than 18 years with decompensated cirrhosis without a history of liver transplantation or hepatocellular carcinoma. We further identified patients with alcoholic cirrhosis vs. non-alcoholic cirrhosis. Primary outcomes included the risk and mortality of portal vein thrombosis in alcoholic cirrhosis. Secondary outcomes included trends of portal vein thrombosis prevalence and mortality in alcoholic cirrhosis, implications of portal vein thrombosis on complications in alcoholic cirrhosis vs. non-alcoholic cirrhosis, and risk of venous thromboembolism in alcoholic cirrhosis. RESULTS Among 1 892 271 patients with decompensated alcoholic cirrhosis, portal vein thrombosis prevalence was 1.3%. Alcoholic cirrhosis was associated with lower risk of portal vein thrombosis (odds ratio 0.76, P < 0.001) and venous thromboembolism (odds ratio 0.69, P < 0.001) compared to non-alcoholic cirrhosis. Portal vein thrombosis contributed to increased mortality (odds ratio 1.19, P < 0.001) in alcoholic cirrhosis. Portal vein thrombosis prevalence among alcoholic cirrhosis increased while mortality declined during the study period. CONCLUSION Thrombotic events including portal vein thrombosis and venous thromboembolism were found in less frequent association with alcoholic cirrhosis compared with non-alcoholic cirrhosis. Despite this, the higher in-hospital mortality found among portal vein thrombosis with alcoholic cirrhosis should prompt careful consideration of management.
Collapse
|
|
22
|
Thromboelastography-targeted management of severe coagulopathy and off-label use of four-factor prothrombin complex concentrate in an infant with massive bleeding. Blood Coagul Fibrinolysis 2020; 31:170-173. [PMID: 31977329 DOI: 10.1097/mbc.0000000000000888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
: A 4-month-old girl initially presented to the pediatric ICU at 9 days old with multiorgan failure and cerebellar hemorrhage secondary to disseminated enteroviral infection and was eventually listed for liver transplant. Due to severe coagulopathy, she developed a hemothorax after line placement. Despite operative exploration and multiple recombinant factor VIIa doses, massive bleeding continued. The bleeding was finally controlled with thromboelastography-targeted platelet and cryoprecipitate transfusion in addition to four-factor prothrombin complex concentrate administration. This management strategy was invaluable in controlling bleeding from an iatrogenic cause.
Collapse
|
|
23
|
Najafi A, Jafarian A, Makarem J, Barzin G, Salimi J, Nasiri-Toosi M, Moini M, Ebrahimi A, Behboudi B, Mohammadpour Z, Shariat Moharari R. Comparison of Coagulation Conditions in Patients With Liver Cirrhosis Due to Primary Sclerosing Cholangitis and Nonbiliary Causes of Cirrhosis Before Orthotopic Liver Transplant. EXP CLIN TRANSPLANT 2020; 18:696-700. [PMID: 32552627 DOI: 10.6002/ect.2018.0374] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Orthotopic liver transplant can be accompanied by an obscure bleeding pattern in patients with severe hepatic malfunction. In the present study, coagulation conditions of patients with cirrhosis of the liver due to primary sclerosing cholangitis and nonbiliary causes of cirrhosis were compared using rotational thromboelastometry assays obtained before orthotopic liver transplant. MATERIALS AND METHODS This case control study analyzed patients who were candidates for orthotopic liver transplant from 2010 to 2016. Eighty patients with cirrhosis of the liver (40 patients with primary sclerosing cholangitis and 40 with nonbiliary causes of cirrhosis) were randomly selected and enrolled into the study. Patients received rotational thromboelastometry assays under anesthesia just before the start of the operation, and results were compared between the 2 patient groups. RESULTS Of 80 patients, 52 were men and 28 were women. In the assays, we found that maximum amplitudes in 10 and in 20 minutes and maximum clot firmness parameters were higher in patients with primary sclerosing cholangitis. The alpha angle and clot formation time were different in the intrinsic and extrinsic assay panels. In the intrinsic assay, we found clotting time to be shorter (P < .05). The average of all parameters in all 3 assays (intrinsic, extrinsic, and fibrinogen contribution) was lower in patients with nonbiliary causes of cirrhosis than in those with primary sclerosing cholangitis. CONCLUSIONS In contrast with previous studies that found that patients with primary sclerosing cholangitis are hypercoagulable, our study observed that they have normal coagulable results. Furthermore, we found that, although mean coagulation indexes in patients with primary sclerosing cholangitis were within normal ranges, in patients with nonbiliary causes of cirrhosis, these indexes were generally lower.
Collapse
Affiliation(s)
- Atabak Najafi
- From the Liver Transplantation Research Center, Imam Khomeini Hospital Complex, and the Department of Anesthesiology and Critical Care, Tehran University of Medical Sciences, Sina Hospital, Tehran, Iran
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
24
|
Davis JPE, Intagliata NM. Anticoagulation in the Hospitalized Patient with Decompensated Cirrhosis: Management of a Delicate Balance. THE CRITICALLY ILL CIRRHOTIC PATIENT 2020:219-236. [DOI: 10.1007/978-3-030-24490-3_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
25
|
Thromboelastography Values Remain Hypercoagulative 6 Months After Obesity Surgery: a Pilot Study. Obes Surg 2019; 28:3943-3949. [PMID: 30083792 DOI: 10.1007/s11695-018-3437-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE Obesity causes a prothrombotic state and is known as a predisposing factor for thromboembolic events. In this pilot study, we assessed the impact of surgery for obesity and the subsequent weight loss on blood coagulation using traditional coagulation tests and thromboelastography (TEG). MATERIAL AND METHODS We studied blood samples from 18 patients receiving bariatric surgery. Besides traditional blood coagulation tests and high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation, the TEG parameters reaction time (R), kinetics time (K), angle (α), maximum amplitude (MA), clot strength (G), and lysis percent at 60 min (LY60) were determined preoperatively and on the first postoperative day and 6 months after surgery. RESULTS Altogether, 54 samples were analyzed. The median MA (71.3 mm), G (12,403.3 d/sc), and hsCRP (3.5 mg/l) were elevated preoperatively. The median hsCRP further increased on the first day postoperatively, but declined to the normal range 6 months after surgery, while MA and G remained elevated. In traditional coagulation tests, there was an increase in median fibrinogen and D-dimer postoperatively. D-dimer normalized (0.4 mg/l) during the study period, while the fibrinogen level (4.1 g/l) remained above the upper limit of normal. CONCLUSIONS Measured by TEG, patients receiving bariatric surgery have hemostatic abnormalities indicating hypercoagulation at the 6-month follow-up visit, suggesting an elevated risk for thromboembolic events for at least 6 months after surgery.
Collapse
|
|
26
|
Thromboelastography Parameters Are Associated with Cirrhosis Severity. Dig Dis Sci 2019; 64:2661-2670. [PMID: 30915655 DOI: 10.1007/s10620-019-05597-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Accepted: 03/19/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND Coagulopathy in cirrhosis represents complex coagulation derangements, and thromboelastography (TEG) measures these complex derangements. AIM We sought to evaluate associations between TEG parameters and validated measures of cirrhosis severity, which have not been previously investigated. MATERIALS AND METHODS Adults with cirrhosis undergoing liver transplant (LT) were identified. Patients had TEG drawn immediately prior to LT. TEG parameters included reaction time (R), kinetic time (K), alpha angle (α), and maximum amplitude (MA). The validated measures of cirrhosis severity were MELD-Na and clinical stage of cirrhosis (classified using history of varices, variceal bleeding, or ascites). Multivariable linear and logistic regression analyses were conducted to evaluate the associations between TEG and stage of cirrhosis and MELD-Na. RESULTS Among 164 patients with cirrhosis, advancing stage of cirrhosis was associated with more hypocoagulable TEG parameters including longer K-time (p = 0.05) and lower MA (p < 0.001). Similarly, with increasing MELD-Na quartiles, K-time was longer (p < 0.001), and both MA and α-angle decreased (p < 0.001, for both). Variceal bleeding within 6 weeks prior to LT was associated with longer R-times (p = 0.02), longer K-times (p = 0.04), smaller α-angle (p = 0.03), and lower MA (p = 0.01). On multivariable analyses, decreasing MA remained statistically significantly associated with advancing stage of cirrhosis and increasing MELD-Na, after adjusting for multiple covariates including platelet count, (p = 0.02 and p < 0.0001, respectively). CONCLUSIONS Hypocoagulable TEG measurements are associated with advancing stage of cirrhosis and increasing MELD-Na among patients with cirrhosis. These data indicate that TEG, as an informative measure of complex hemostatic function, may be a useful objective marker of liver disease severity in cirrhosis.
Collapse
|
|
27
|
Yoon J, Cheon J, Choi YJ, Byeon G, Ahn J, Choi E, Park JY. The correlation between conventional coagulation tests and thromboelastography in each phase of liver transplantation. Clin Transplant 2019; 33:e13478. [DOI: 10.1111/ctr.13478] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 12/18/2018] [Accepted: 12/23/2018] [Indexed: 11/27/2022]
Affiliation(s)
- Ji‐Uk Yoon
- Department of Anesthesia and Pain Medicine Pusan National University Yangsan Hospital Yangsan Korea
- Department of Anesthesia and Pain Medicine, School of Medicine Pusan National University Yangsan Korea
| | - Ji‐Hyun Cheon
- Department of Anesthesia and Pain Medicine, School of Medicine Pusan National University Yangsan Korea
| | - Yoon Ji Choi
- Department of Anesthesiology and Pain Medicine Korea University Ansan Hospital Ansan Korea
| | - Gyeong‐Jo Byeon
- Department of Anesthesia and Pain Medicine Pusan National University Yangsan Hospital Yangsan Korea
- Department of Anesthesia and Pain Medicine, School of Medicine Pusan National University Yangsan Korea
| | - Ji‐Hye Ahn
- Department of Dental Anesthesia and Pain Medicine, School of Dentistry Pusan National University, Dental Research Institute Yangsan Korea
| | - Eun‐Ji Choi
- Department of Anesthesia and Pain Medicine Pusan National University Yangsan Hospital Yangsan Korea
- Department of Anesthesia and Pain Medicine, School of Medicine Pusan National University Yangsan Korea
| | - Ju Yeon Park
- Department of Anesthesia and Pain Medicine Pusan National University Yangsan Hospital Yangsan Korea
- Department of Anesthesia and Pain Medicine, School of Medicine Pusan National University Yangsan Korea
| |
Collapse
|
|
28
|
Campbell RAS, Thomson EM, Beattie C. Effect of Liver Disease Etiology on ROTEM Profiles in Patients Undergoing Liver Transplantation. Transplant Proc 2019; 51:783-789. [PMID: 30979465 DOI: 10.1016/j.transproceed.2018.12.030] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 12/27/2018] [Accepted: 12/28/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Coagulation abnormalities in liver transplant patients are complex and may be related to the underlying liver disease. We evaluated the effects of disease etiology on whole-blood rotational thromboelastometry (ROTEM; Pentapharm GmbH, Munich, Germany) profile and association with thrombotic complications following liver transplantation. METHODS Analysis of perioperative data from patients undergoing liver transplantation between January 1, 2012 and December 31, 2016. Patients were grouped based on the biology of their underlying liver disease: hepatocellular carcinoma (HCC), biliary etiology, and non-biliary etiology. The primary outcome was the EXTEM A10 value of the pre-incision ROTEM. Secondary outcomes included associations between EXTEM A10 value and incidence of postoperative thrombotic complications. RESULTS Three hundred fifty patients met the eligibility criteria: 60 had biliary etiologies, 203 had non-biliary etiologies, and 87 had HCC. EXTEM A10 values were significantly higher in patients with biliary etiologies than those with non-biliary etiologies (mean difference, 13.8; 95% CI: 10.1 to 17.5; P = .001) and those with HCC (mean difference, 10.4; 95% CI: 6.2 to 14.7; P = .001). Patients with non-biliary etiologies had slightly higher values than those with HCC (mean difference, -3.3; 95% CI: -6.6 to -0.1; P = .04). Higher values for biliary etiologies remained after adjusting for liver disease severity, platelet count, and fibrinogen level. There was no significant difference in EXTEM A10 values between patients who suffered thrombotic complications and those who did not (mean difference: 4.3, 95% CI: -1.3 to 9.9, P = .13). CONCLUSION Patients with biliary diseases demonstrated higher EXTEM A10 values compared to those with non-biliary diseases or HCC. This was not fully explained by differences in disease severity, platelet count, or fibrinogen level. Pre-incision EXTEM A10 values do not predict incidence of postoperative thrombotic complications.
Collapse
Affiliation(s)
| | - E M Thomson
- Department of Anaesthetics, Critical Care and Pain Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK
| | - C Beattie
- Department of Anaesthetics, Critical Care and Pain Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK
| |
Collapse
|
|
29
|
Patients With Budd-Chiari Syndrome Have Variable Coagulation Status on Thromboelastography at Diagnosis. J Clin Exp Hepatol 2019; 9:460-467. [PMID: 31516262 PMCID: PMC6728540 DOI: 10.1016/j.jceh.2018.10.002] [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: 12/08/2017] [Accepted: 10/18/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND & AIMS Budd-Chiari Syndrome (BCS) is considered a thrombophilic state, and most patients with BCS have thrombophilic disorder. Liver dysfunction-related coagulopathy makes coagulation function unpredictable in BCS. Thromboelastography (TEG) assesses the dynamics, strength, and stability of clot formation. We conducted a pilot study using TEG to evaluate coagulation status in patients with BCS. METHODS Fifty-one patients with newly diagnosed BCS (age 32.3 [10.7] years; 23 men) underwent TEG (TEG®5000 Hemostasis Analyzer®, USA), and its components were analyzed and correlated with clinical profile and thrombophilic disorders. Patients who had received anticoagulation, antiplatelet drugs, or radiological intervention were excluded. RESULTS Twenty-nine patients had normal TEG, 11 had procoagulant TEG, and 11 had hypocoagulant TEG. Among patients with hypocoagulant TEG, Coagulation Index (CI) was < -3 in 11 patients, R was >8 min in 6 patients, K was >3 min in 9 patients, alpha <55 in 9 patients, and MA <51 in 7 patients; among those with hypercoagulant TEG, CI was >3 in 3 patients, R < 2 min in 2 patients, K <1 min in 2 patients, alpha >78 in none, and MA >69 mm in 7 patients. TEG findings were similar in patients with and without thrombophilic disorder. The mean platelet count (1.75, 2.22, and 1.79 × 105/mm3; P = 0.13) and international normalized ratio (1.27, 1.34, and 1.28, P = 0.69) were similar in those with procoagulant, normal, and hypocoagulant TEG. Two patients in Rotterdam class-III had abnormal LY30. Other clinical parameters did not correlate with TEG findings. CONCLUSION Patients with BCS are heterogeneous with respect to coagulation status, with one-fifth of patients are hypocoagulant on TEG. Patients with advanced disease may have accelerated fibrinolysis.
Collapse
Key Words
- BCS, Budd-Chiari Syndrome
- CT, Computed Tomography
- CTP, Child-Turcotte-Pugh
- INR, International Normalized Ratio
- IVC, Inferior Vena Cava
- JAK-2, Janus Kinase-2
- MELD, Model for End-Stage Liver Disease
- MRI, Magnetic Resonance Imaging
- MTHFR, Methylene tetrahydrofolatereductase
- PNH, Paroxysmal Nocturnal Hemoglobinuria
- PT, Prothrombin Time
- TEG, Thromboelastography
- aPTT, Partial Thromboplastin Time
- cirrhosis
- gastrointestinal hemorrhage
- hepatic venous outflow tract obstruction
- portal hypertension
- varices
Collapse
|
|
30
|
Blasi A, Calvo A, Prado V, Reverter E, Reverter JC, Hernández-Tejero M, Aziz F, Amoros A, Cardenas A, Fernández J. Coagulation Failure in Patients With Acute-on-Chronic Liver Failure and Decompensated Cirrhosis: Beyond the International Normalized Ratio. Hepatology 2018; 68:2325-2337. [PMID: 29790188 DOI: 10.1002/hep.30103] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Accepted: 05/14/2018] [Indexed: 12/22/2022]
Abstract
Balanced hemostasis with hypocoagulable and hypercoagulable features may occur in acute-on-chronic liver failure (ACLF). The characteristics and prognostic impact of the coagulation profile in ACLF are unknown. Consecutive patients with ACLF (n = 36) and acute decompensation (AD; n = 24) were included. Blood samples for thromboelastometry (TE) were obtained at admission and 72 hours thereafter. The coagulation profile was evaluated in patients with and without ACLF and in those with and without systemic inflammatory response syndrome. The impact of the coagulation profile on transfusion requirements, bleeding events, and short-term survival was assessed. At admission, patients with ACLF showed more hypocoagulable characteristics compared to AD subjects, with prolonged time to initial fibrin formation and clot formation time and decreased maximum clot firmness and alpha-angle values. TE parameters worsened at 72 hours in ACLF but improved in patients with AD. Prevalence of a hypocoagulable profile (three or more TE parameters outside range) was significantly higher in patients with ACLF either at admission (61% versus 29% in AD; P = 0.03) or during follow-up. Hypocoagulability correlated with systemic inflammation and was associated with higher 28-day (45% versus 16%; P = 0.02) and 90-day (52% versus 19%; P = 0.01) mortality rates but not with transfusion requirements or bleeding. Prolonged time to initial fibrin formation (extrinsic TE assay >80 seconds) and Model for End-Stage Liver Disease score at baseline were independent predictors of 28-day mortality. Conclusion: Patients with ACLF frequently show hypocoagulable features with prolonged time to initial fibrin formation and clot formation time and reduced clot firmness; these alterations worsen after admission, correlate with systemic inflammation, and translate into higher short-term mortality; hypofibrinolysis could contribute to organ failure in ACLF.
Collapse
Affiliation(s)
- Annabel Blasi
- Anesthesiology Department, Hospital Clínic, and University of Barcelona, Spain.,Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) y Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD)
| | - Andrea Calvo
- Anesthesiology Department, Hospital Clínic, and University of Barcelona, Spain
| | - Verónica Prado
- Liver Unit, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, and University of Barcelona
| | - Enric Reverter
- Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) y Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD).,Liver Unit, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, and University of Barcelona
| | | | - María Hernández-Tejero
- Liver Unit, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, and University of Barcelona
| | - Fátima Aziz
- Liver Unit, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, and University of Barcelona
| | - Alex Amoros
- European Foundation for the Study of Chronic Liver Failure
| | - Andres Cardenas
- Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) y Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD).,GI/Liver Unit, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, and University of Barcelona, Barcelona, Spain
| | - Javier Fernández
- Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS) y Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD).,Liver Unit, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, and University of Barcelona.,European Foundation for the Study of Chronic Liver Failure
| |
Collapse
|
|
31
|
Veronese LR, Miller M, Spearman WC. Thromboelastography in mild, chronic liver disease: challenging conventional coagulation tests preceding liver biopsy. SOUTHERN AFRICAN JOURNAL OF ANAESTHESIA AND ANALGESIA 2018. [DOI: 10.1080/22201181.2018.1510234] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- LR Veronese
- Department of Anaesthesia and Perioperative Medicine, University of Cape Town, Cape Town, South Africa
| | - M Miller
- Department of Anaesthesia and Perioperative Medicine, University of Cape Town, Cape Town, South Africa
| | - WC Spearman
- Division of Hepatology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| |
Collapse
|
|
32
|
Abuelkasem E, Tanaka KA, Planinsic RM. Recent update on coagulation management and hemostatic therapies in liver transplantation. Minerva Anestesiol 2018; 84:1070-1080. [DOI: 10.23736/s0375-9393.18.12487-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
|
|
33
|
Katsounas A, Canbay A. Intensive Care Therapy for Patients with Advanced Liver Diseases. Visc Med 2018; 34:283-289. [PMID: 30345286 DOI: 10.1159/000492088] [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] [Indexed: 12/14/2022] Open
Abstract
Decompensated cirrhosis is characterized by high hospitalization rates and costs, frequent readmissions, and poor short-term survival. Patients admitted to the hospital with acute variceal bleeding and/or hepatic encephalopathy and/or renal dysfunction are at serious risk for developing infection and/or sepsis; in turn, this renders them highly susceptible to the development of multi-system organ failure. The lack of standardized intensive care unit management protocols in patients with cirrhosis along with only few data reports from longitudinal clinical trials makes it difficult for hepatologists and critical care specialists to provide uniform evidence for clinical practice that could safely consolidate favorable outcomes such as lower hospitalization rates and/or mortality. Based on a rigorous online search of the scientific literature as well as a longtime clinical experience of the authors in the field of hepatology and critical care medicine, this work represents a focused effort to elucidate the specific bio-morbidity of advanced liver diseases in relation to the aforementioned challenges in clinical management. Further meta-analyses and/or systematic reviews are needed to enable clinicians to develop more effective strategies to bridge patients with decompensated liver disease to recompensation or liver transplantation.
Collapse
Affiliation(s)
- Antonios Katsounas
- Department for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany
| | - Ali Canbay
- Department for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany
| |
Collapse
|
|
34
|
George G, Manatasahit W, Balasubramanian M, Navarro V. Reproducibility of TEG Parameters in Stable Cirrhotics. Lab Med 2018. [PMID: 29529240 DOI: 10.1093/labmed/lmx041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background Thromboelastography (TEG) has become the standard of care in liver-transplant surgery to identify real-time abnormalities in the coagulation cascade. To our knowledge, no studies have been performed to measure the intrasubject reproducibility of TEG parameters in cirrhotic patients. Objective To perform a validation study to determine the reproducibility of TEG in cirrhosis. Methods We recruited 30 patients with stable cirrhosis and tested 25 of them. Two blood specimens were drawn 1 hour apart; we measured the TEG parameters R time, K time, angle, maximum amplitude (MA), and functional fibrinogen (FF), along with conventional coagulation parameters. Reproducibility was assessed using the intraclass coefficient test. The TEG parameters were then compared with conventional coagulation test results. Results The K time, angle, MA, and FF results showed excellent reproducibility (r > 0.7; P <.001). Platelets and fibrinogen correlated with MA and K time; prothrombin time (PT) and activated partial thromboplastin time (aPTT) were inversely correlated with MA. Conclusion All parameters were reproducible when measured 1 hour apart. TEG may be suitable to investigate coagulation characteristics in patients with clinically stable cirrhosis; however, further studies are needed in patients with more advanced cirrhosis, in whomblood product use may be more prevalent.
Collapse
Affiliation(s)
- Gemlyn George
- Department of Medicine, Einstein Medical Center, Philadelphia, PA
| | | | | | - Victor Navarro
- Department of Clinical Pathology, Einstein Medical Center, Philadelphia, PA
| |
Collapse
|
|
35
|
Shimauchi T, Yamaura K, Higashi M, Abe K, Yoshizumi T, Hoka S. Fibrinolysis in Living Donor Liver Transplantation Recipients Evaluated Using Thromboelastometry: Impact on Mortality. Transplant Proc 2018; 49:2117-2121. [PMID: 29149971 DOI: 10.1016/j.transproceed.2017.09.025] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 09/05/2017] [Accepted: 09/23/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Inadequate hemostasis during living donor liver transplantation (LDLT) is mainly due to coagulopathy but may also include fibrinolysis. The purpose of this study was to determine the incidence of fibrinolysis and assess its relevance to mortality in LDLT. METHODS The incidence and prognosis of fibrinolysis were retrospectively studied in 76 patients who underwent LDLT between April 2010 and February 2013. Fibrinolysis was evaluated and defined by maximum lysis (ML) >15% within a 60-minute run time using thromboelastometry (ROTEM). RESULTS Fibrinolysis was observed in 19 of the 76 (25%) patients before the anhepatic (pre-anhepatic) phase and was developed in 24 (32%) patients during and after the anhepatic (post-anhepatic) phase. In these 43 patients who had fibrinolysis, spontaneous recovery occurred in 29 patients (73%) within 3 hours after reperfusion of the liver graft. Recovery with tranexamic acid was noted in 2 patients with fibrinolysis in the post-anhepatic phase. Thrombosis in the portal vein and liver artery was noted in 14 patients, and the incidence was significantly greater in patients with post-anhepatic fibrinolysis than in those with pre-anhepatic fibrinolysis (P = .0017). Fibrinolysis that developed in the pre-anhepatic phase was associated with increased 30-day and 6-month mortalities (P = .0003 and .0026, respectively). CONCLUSIONS Fibrinolysis existed and developed in a large percentage of patients during LDLT. Thrombosis in the portal vein and hepatic artery was more common in patients with fibrinolysis in the post-anhepatic phase. Fibrinolysis that developed in the pre-anhepatic phase was associated with increased 30-day and 6-month mortalities.
Collapse
Affiliation(s)
- T Shimauchi
- Department of Anaesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - K Yamaura
- Operating Rooms, Kyushu University Hospital, Fukuoka, Japan; Department of Anaesthesiology, Fukuoka University School of Medicine, Fukuoka, Japan.
| | - M Higashi
- Operating Rooms, Kyushu University Hospital, Fukuoka, Japan
| | - K Abe
- Department of Anaesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - T Yoshizumi
- Department of Surgery and Science, Graduate school of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - S Hoka
- Department of Anaesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| |
Collapse
|
|
36
|
Utility of Viscoelastic Assays Beyond Coagulation: Can Preoperative Thrombelastography Indices Predict Tumor Histology, Nodal Disease, and Resectability in Patients Undergoing Pancreatectomy? J Am Coll Surg 2018; 227:55-62. [PMID: 29605725 DOI: 10.1016/j.jamcollsurg.2018.03.031] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Revised: 02/16/2018] [Accepted: 03/13/2018] [Indexed: 01/08/2023]
Abstract
BACKGROUND Hypercoagulability and malignancy have been linked since the 1860s. However, the impact of different neoplasms on multiple components of the coagulation system remains poorly understood. Thrombelastography (TEG) enables measurement of coagulation incorporating clotting through fibrinolysis. We hypothesize that specific TEG indices that are associated with hypercoagulability can be appreciated in patients with adenocarcinoma undergoing pancreatic resection. STUDY DESIGN Blood samples were obtained from patients undergoing pancreatic resection before surgical incision and assayed with TEG. The 4 indices of coagulation measured by TEG included in the analysis were R time, angle, maximum amplitude, and lysis at 30 minutes. Patient tumor type, nodal disease, and mass resectability were contrasted with TEG indices. RESULTS One hundred patients were enrolled over 18 months. The majority (63%) of patients had adenocarcinoma. Patients with adenocarcinoma had increased angle compared with other lesions (49 degrees [interquartile range {IQR} 37 to 59 degrees] vs 43 degrees [IQR 32 to 49 degrees]; p = 0.011). When excluding patients that underwent neoadjuvant therapy, patients with adenocarcinoma had shorter R times (13 minutes [IQR 9 to 16 minutes] vs 14 minutes [IQR 12 to 18 minutes]; p = 0.051), steeper angles (49 degrees [IQR 40 to 59 degrees] vs 43 degrees [IQR 32 to 49 degrees]; p = 0.010), and higher maximum amplitude (67 mm [IQR 61 to 69 mm] vs 62 mm [IQR 57 to 67 mm]; p = 0.017). Nodal disease was associated with a significantly increased angle (49 degrees [IQR 42 to 59 degrees] vs 40 degrees [IQR 32 to 50 degrees]; p = 0.002) and maximum amplitude (64 mm [IQR 61 to 69 mm] vs 62 mm [IQR 56 to 67 mm]; p = 0.017). Patients who underwent successful mass resection had longer R times (14 minutes [IQR 11 to 17 minutes] vs 10 minutes [IQR 9 to 15]; p = 0.033) and shorter angles (44 degrees [IQR 35 to 55 degrees] vs 58 degrees [IQR 45 to 66 degrees]; p = 0.025). CONCLUSIONS Patients with adenocarcinoma undergoing pancreatic resection have multiple TEG abnormalities consistent with hypercoagulability. These TEG outputs are associated with tumor type, nodal disease, and probability of a successful resection. The use of preoperative TEG has the potential to aid surgeon and patient discussions on anticipated disease burden and prognosis before resection.
Collapse
|
|
37
|
Abstract
Platelets are key players in thrombosis and hemostasis. Alterations in platelet count and function are common in liver disease, and may contribute to bleeding or thrombotic complications in liver diseases and during liver surgery. In addition to their hemostatic function, platelets may modulate liver diseases by mechanisms that are incompletely understood. Here, we present clinical evidence for a role of platelets in the progression of chronic and acute liver diseases, including cirrhosis, acute liver failure, and hepatocellular carcinoma. We also present clinical evidence that platelets promote liver regeneration following partial liver resection. Subsequently, we summarize studies in experimental animal models that support these clinical observations, and also highlight studies that are in contrast with clinical observations. The combined results of clinical and experimental studies suggest that platelets may be a therapeutic target in the treatment of liver injury and repair, but the gaps in our understanding of mechanisms involved in platelet-mediated modulation of liver diseases call for caution in clinical application of these findings.
Collapse
Affiliation(s)
- Ton Lisman
- Section of Hepatobiliary Surgery and Liver Transplantation and Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - James P. Luyendyk
- Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan, USA
| |
Collapse
|
|
38
|
Stravitz RT. Hematological Issues in Liver Disease. HEPATIC CRITICAL CARE 2018:163-178. [DOI: 10.1007/978-3-319-66432-3_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
39
|
Abstract
It was thought that a high international normalized ratio predicted bleeding in patients with chronic liver disease (CLD) and patients were "autoanticoagulated." Contrary to this belief, while patients with CLD experienced bleeding, they also developed thromboses. In the last decade, the prevailing literature challenged the idea that an elevated international normalized ratio increased bleeding risk. The global assays of coagulation such as thromboelastography (TEG)/rotational thromboelastometry and thrombin generation assays provide additional insight into coagulation processes. It has become apparent that a parallel reduction of procoagulant and anticoagulant factors leave patients in a new "balanced" state, albeit a fragile one, where the balance can be easily disrupted. The inherent differences in coagulation between children and adults such as differences in levels of procoagulant and anticoagulant factors, underlying liver disease, and the paucity of studies in children make extrapolation of these findings to the pediatric population problematic. Ultimately, this is an area that requires further investigation to avoid inappropriate use of blood products and medication.
Collapse
|
|
40
|
Blaine KP, Sakai T. Viscoelastic Monitoring to Guide Hemostatic Resuscitation in Liver Transplantation Surgery. Semin Cardiothorac Vasc Anesth 2017; 22:150-163. [PMID: 29099334 DOI: 10.1177/1089253217739121] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Coagulopathic bleeding must be anticipated during liver transplantation (LT) surgery. Patients with end-stage liver disease (ESLD) often present with disease-related hematologic disturbances, including the loss of hepatic procoagulant and anticoagulant clotting factors and thrombocytopenia. Transplantation surgery itself presents additional hemostatic changes, including hyperfibrinolysis. Viscoelastic monitoring (VEM) is often used to provide targeted, personalized hemostatic therapies for complex bleeding states including cardiac surgery and major trauma. The use in these coagulopathic conditions led to its application to LT, although the mechanisms of coagulopathy in these patients are quite different. While VEM is often used during transplant surgeries in Europe and North America, evidence supporting its use is limited to a few small clinical studies. The theoretical and clinical applications of the standard and specialized VEM assays are discussed in the setting of LT and ESLD.
Collapse
Affiliation(s)
- Kevin P Blaine
- 1 Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
| | - Tetsuro Sakai
- 2 University of Pittsburgh Medical Center Health System, Pittsburgh, PA, USA
| |
Collapse
|
|
41
|
Olson JC, Karvellas CJ. Critical care management of the patient with cirrhosis awaiting liver transplant in the intensive care unit. Liver Transpl 2017; 23:1465-1476. [PMID: 28688155 DOI: 10.1002/lt.24815] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Revised: 06/28/2017] [Accepted: 06/29/2017] [Indexed: 02/07/2023]
Abstract
Patients with cirrhosis who are awaiting liver transplantation (LT) are at high risk for developing critical illnesses. Current liver allocation policies that dictate a "sickest first" approach coupled with a mismatch between need and availability of organs result in longer wait times, and thus, patients are becoming increasingly ill while awaiting organ transplantation. Even patients with well-compensated cirrhosis may suffer acute deterioration; the syndrome of acute-on-chronic liver failure (ACLF) results in multisystem organ dysfunction and a marked increase in associated short-term morbidity and mortality. For patients on transplant waiting lists, the development of multisystem organ failure may eliminate candidacy for transplant by virtue of being "too sick" to safely undergo transplantation surgery. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (eg, infection and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo LT. Management of the critically ill ACLF patient awaiting transplantation is best accomplished by multidisciplinary teams with expertise in critical care and transplant medicine. Such teams are well suited to address the needs of this unique patient population and to identify patients who may be too ill to proceed to transplantation surgery. The focus of this review is to identify the common complications of ACLF and to describe our approach management in critically ill patients awaiting LT in our centers. Liver Transplantation 23 1465-1476 2017 AASLD.
Collapse
Affiliation(s)
- Jody C Olson
- Divisions of Critical Care Medicine and Hepatology, University of Kansas Medical Center, Kansas City, KS
| | - Constantine J Karvellas
- Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada.,Division of Division of Gastroenterology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| |
Collapse
|
|
42
|
Hugenholtz GC, Lisman T, Stravitz RT. Thromboelastography does not predict outcome in different etiologies of cirrhosis. Res Pract Thromb Haemost 2017; 1:275-285. [PMID: 30046697 PMCID: PMC6058258 DOI: 10.1002/rth2.12037] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Accepted: 06/28/2017] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND New laboratory tests that measure global hemostasis indicate generally preserved hemostatic function in patients with cirrhosis. It is not known whether normal hemostatic function is maintained across various subsets of patients. OBJECTIVES In the present study, we investigated clot generation and clot lysis kinetics in a large group of patients with different etiologies of disease. PATIENTS/METHODS Blood samples of 270 patients with cirrhosis were studied using thromboelastography (TEG), which measures the dynamic and physical properties of clot formation and lysis in whole blood. TEG parameters of different subsets of the patient population were compared. Correlations with routine laboratory tests as well as clinical outcomes were explored. RESULTS Overall, TEG parameters were normal and similar between underlying disease etiologies. A proportion of subjects showed hypocoagulable features, with the exception of patients with cholestatic cirrhosis in whom TEG readings showed hypercoagulable features. In all groups, K-time, α-Angle, and MA correlated well with platelet counts and fibrinogen plasma levels. After a mean follow-up of 2 years and 11 months, 31 patients had experienced a bleeding event, 8 had developed thrombosis, and 173 patients (64%) had undergone liver transplantation and/or had died. TEG baseline parameters were similar between patients subdivided according to outcome. CONCLUSIONS TEG parameters reflected generally preserved function of the hemostatic system in patients with cirrhosis, with hypo- and hypercoagulable features in subsets of patients with specific underlying disease etiologies. Abnormalities in TEG parameters did however not predict bleeding, thrombosis, or risk of liver transplantation and/or death.
Collapse
Affiliation(s)
- Greg C.G. Hugenholtz
- Department of SurgerySurgical Research LaboratoryUniversity of GroningenUniversity of Medical Center GroningenGroningenthe Netherlands
| | - Ton Lisman
- Department of SurgerySurgical Research LaboratoryUniversity of GroningenUniversity of Medical Center GroningenGroningenthe Netherlands
- Department of SurgerySection of Hepatobiliary Surgery and Liver TransplantationUniversity of GroningenUniversity of Medical Center GroningenGroningenthe Netherlands
| | - Richard Todd Stravitz
- Section of Hepatology and Hume‐Lee Transplant CenterVirginia Commonwealth UniversityRichmondVAUSA
| |
Collapse
|
|
43
|
Liu K, Strasser SI, Koorey DJ, Leong RW, Solomon M, McCaughan GW. Interactions between primary sclerosing cholangitis and inflammatory bowel disease: implications in the adult liver transplant setting. Expert Rev Gastroenterol Hepatol 2017. [PMID: 28627935 DOI: 10.1080/17474124.2017.1343666] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease which is associated with inflammatory bowel disease (IBD) in most cases. As there is currently no medical therapy which alters the natural history of PSC, liver transplantation may be required. Areas covered: We searched for articles in PubMed and critically reviewed current literature on the interrelationship between PSC and IBD with a specific focus on considerations for patients in the liver transplant setting. Expert commentary: PSC is an uncommon disease which limits available studies to be either retrospective or contain relatively small numbers of patients. Based on observations from these studies, the behavior and complications of PSC and IBD impact on each other both before and after a liver transplant. Both these autoimmune conditions and their associated cancer risk also influence patient selection for transplantation and may be impacted by immunosuppression use post-transplant. Hence, a complex interplay exists between PSC, IBD and liver transplantation which requires clarification with ongoing research.
Collapse
Affiliation(s)
- Ken Liu
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia.,c Liver Injury and Cancer Program, Centenary Institute , The University of Sydney , Sydney , NSW , Australia
| | - Simone I Strasser
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia
| | - David J Koorey
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia
| | - Rupert W Leong
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,d Gastroenterology and Liver Services , Concord Hospital , Sydney , NSW , Australia
| | - Michael Solomon
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,e Department of Colorectal Surgery , Royal Prince Alfred Hospital , Sydney , NSW , Australia
| | - Geoffrey W McCaughan
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia.,c Liver Injury and Cancer Program, Centenary Institute , The University of Sydney , Sydney , NSW , Australia
| |
Collapse
|
|
44
|
Lisman T, Porte RJ. Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases. Res Pract Thromb Haemost 2017; 1:150-161. [PMID: 30046685 PMCID: PMC6058283 DOI: 10.1002/rth2.12028] [Citation(s) in RCA: 92] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 06/21/2017] [Indexed: 12/14/2022] Open
Abstract
Patients with liver diseases may develop alterations in all components of the hemostatic system. Thrombocytopenia, low levels of coagulation factors and inhibitors, low levels of fibrinolytic proteins, and increased levels of endothelial-derived proteins such as von Willebrand factor are all part of the coagulopathy of liver disease. Due to concomitant changes in pro- and antihemostatic drivers, the net effects of these complex hemostatic changes have long been unclear. According to current concepts, the hemostatic system of patients with liver disease is in an unstable balance, which explains the occurrence of both bleeding and thrombotic complications. This review will discuss etiology and management of bleeding and thrombosis in liver disease and will outline unsolved clinical questions. In addition, we will discuss the role of intrahepatic activation of coagulation for progression of liver disease, a novel paradigm with potential consequences for the general management of patients with liver disease.
Collapse
Affiliation(s)
- Ton Lisman
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver TransplantationDepartment of SurgeryUniversity of GroningenUniversity Medical Center GroningenGroningenthe Netherlands
| | - Robert J. Porte
- Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver TransplantationDepartment of SurgeryUniversity of GroningenUniversity Medical Center GroningenGroningenthe Netherlands
| |
Collapse
|
|
45
|
Lisman T, Bernal W. Management of Hemostatic Disorders in Patients With Advanced Liver Disease Admitted to an Intensive Care Unit. Transfus Med Rev 2017; 31:245-251. [DOI: 10.1016/j.tmrv.2017.06.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Revised: 05/19/2017] [Accepted: 06/20/2017] [Indexed: 02/07/2023]
|
|
46
|
Romecín P, Navarro EG, Ortiz MC, Iyú D, García-Estañ J, Atucha NM. Bile Acids Do Not Contribute to the Altered Calcium Homeostasis of Platelets from Rats with Biliary Cirrhosis. Front Physiol 2017. [PMID: 28638347 PMCID: PMC5461275 DOI: 10.3389/fphys.2017.00384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state and related to an enhanced intracellular calcium release evoked by thrombin and an increased amount of calcium stored in the intracellular organelles. In the present study we have investigated the role of bile acids in those alterations of the BDL cirrhotic model. Cholic acid (CA) or deoxycholic acid (DCA) did not change P-selectin expression or platelet aggregation in any group but elevated baseline platelet calcium levels. Incubation with both bile acids reduced calcium release after stimulation with thrombin in the absence of extracellular calcium. Pretreatment with CA but not with DCA reduced significantly thrombin-induced calcium entry in all three experimental groups. The capacitative calcium entry was also significantly lower in platelets pretreated with both bile acids. The simultaneous addition of thapsigargin and ionomycin to estimate the total amount of calcium in platelet internal stores was decreased by pretreatment with both CA and DCA, although these changes were significantly different in the control rats only with CA and in the BDL platelets with DCA. These results indicate that CA and DCA reduce calcium movements in platelets of control and BDL animals, thus suggesting that bile acids do not participate in the alterations observed in the BDL cirrotic model.
Collapse
|
|
47
|
Dumitrescu G, Januszkiewicz A, Ågren A, Magnusson M, Wahlin S, Wernerman J. Thromboelastometry: Relation to the severity of liver cirrhosis in patients considered for liver transplantation. Medicine (Baltimore) 2017; 96:e7101. [PMID: 28591054 PMCID: PMC5466232 DOI: 10.1097/md.0000000000007101] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The severity of liver disease is assessed by scoring systems, which include the conventional coagulation test prothrombin time-the international normalized ratio (PT-INR). However, PT-INR is not predictive of bleeding in liver disease and thromboelastometry (ROTEM) has been suggested to give a better overview of the coagulation system in these patients. It has now been suggested that coagulation as reflected by tromboelastomety may also be used for prognostic purposes. The objective of our study was to investigate whether thrombelastometry may discriminate the degree of liver insufficiency according to the scoring systems Child Pugh and Model for End-stage Liver Disease (MELD).Forty patients with chronic liver disease of different etiologies and stages were included in this observational cross-sectional study. The severity of liver disease was evaluated using the Child-Pugh score and the MELD score, and blood samples for biochemistry, conventional coagulation tests, and ROTEM were collected at the time of the final assessment for liver transplantation. Statistical comparisons for the studied parameters with scores of severity were made using Spearman correlation test and receiver-operating characteristic (ROC) curves.Spearman correlation coefficients indicated that the thromboelastometric parameters did not correlate with Child-Pugh or MELD scores. The ROC curves of the thromboelastometric parameters could not differentiate advanced stages from early stages of liver cirrhosis.Standard ROTEM cannot discriminate the stage of chronic liver disease in patients with severe chronic liver disease.
Collapse
Affiliation(s)
- Gabriel Dumitrescu
- Department of Anesthesia and Intensive Care Medicine, Karolinska University Hospital
| | - Anna Januszkiewicz
- Department of Anesthesia and Intensive Care Medicine, Karolinska University Hospital
| | - Anna Ågren
- Department of Medicine, Division of Hematology, Coagulation Unit, Karolinska University Hospital
| | - Maria Magnusson
- CLINTEC, Division of Pediatrics, Astrid Lindgren Children's Hospital
- MMK, Clinical Chemistry and Blood Coagulation Research, Karolinska Institute
| | - Staffan Wahlin
- Division of Hepatology, Centre for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Jan Wernerman
- Department of Anesthesia and Intensive Care Medicine, Karolinska University Hospital
| |
Collapse
|
|
48
|
Shin KH, Kim IS, Lee HJ, Kim HH, Chang CL, Hong YM, Yoon KT, Cho M. Thromboelastographic Evaluation of Coagulation in Patients With Liver Disease. Ann Lab Med 2017; 37:204-212. [PMID: 28224766 PMCID: PMC5339092 DOI: 10.3343/alm.2017.37.3.204] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Revised: 09/14/2016] [Accepted: 01/23/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The aims of this study were to investigate the parameters of thromboelastography (TEG) for evaluating coagulopathy and to reveal an association with disease severity and/or transfusion requirement in patients with chronic liver disease (CLD) in a clinical laboratory setting. METHODS We enrolled two groups of adult patients with cirrhotic (N=123) and non-cirrhotic liver disease (N=52), as well as 84 healthy controls. Reaction time (R), kinetic time (K), α-angle (α), maximal amplitude (MA), and coagulation index (CI) were measured with kaolin-activated citrated blood with the TEG 5000 system (Haemonetics Corporation, USA). Platelet count, prothrombin time international normalized ratio (PT INR), albumin, bilirubin, and creatinine were simultaneously measured. The CLD severity was calculated by using the Child-Pugh (C-P) and Model for End-stage Liver Disease (MELD) scores. Transfusion history was also reviewed. RESULTS All TEG parameters, PT INR, and platelet count in the cirrhotic group showed significant differences from those in other groups. At least one or more abnormal TEG parameters were identified in 17.3% and 44.7% of patients in the non-cirrhotic and cirrhotic group, respectively. Patients with cirrhotic disease had hypocoagulability. A weak correlation between R and PT INR (r=0.173) was noted. The TEG parameters could not predict CLD severity using the C-P and MELD scores. Patients with normal TEG parameters did not receive transfusion. CONCLUSIONS Clinical application of TEG measurements in CLD can be informative for investigating coagulopathy or predicting the risk of bleeding. Further studies are warranted.
Collapse
Affiliation(s)
- Kyung Hwa Shin
- Department of Laboratory Medicine, Pusan National University School of Medicine and Biomedical Research Institute Research Institute, Pusan National University Hospital, Busan, Korea
| | - In Suk Kim
- Department of Laboratory Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
| | - Hyun Ji Lee
- Department of Laboratory Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Hyung Hoi Kim
- Department of Laboratory Medicine, Pusan National University School of Medicine and Biomedical Research Institute Research Institute, Pusan National University Hospital, Busan, Korea
| | - Chulhun L Chang
- Department of Laboratory Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Young Mi Hong
- Department of Internal Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Mong Cho
- Department of Internal Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| |
Collapse
|
|
49
|
Abstract
Liver diseases may be accompanied by profound changes in the hemostatic system including thrombocytopenia, decreased plasma levels of pro- and anticoagulants, and alterations in plasma levels of fibrinolysis. The net effect of the hemostatic changes in chronic and acute liver diseases is a hemostatic system that is in relative balance due to the simultaneous decline in pro- and antihemostatic drivers. A unique category of liver diseases are those induced by pregnancy. In acute fatty liver of pregnancy, profound hemostatic changes occur, which may be caused by a combination of liver failure and disseminated intravascular coagulation. Hemostatic changes in preeclampsia and HELLP syndrome are dominated by thrombocytopenia, although alterations in plasmatic coagulation may also occur. Post-partum bleeds, bleeding from cesarean section wounds, and hepatobiliary bleeds may occur in both patient groups. Patients with intrahepatic cholestasis of pregnancy do not show clinically relevant hemostatic alterations, despite biochemical evidence of liver injury.
Collapse
Affiliation(s)
- Ton Lisman
- Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
| | - William Bernal
- Liver Intensive Care Unit, Institute of Liver Studies, Kings College Hospital, Denmark Hill, London, United Kingdom
| |
Collapse
|
|
50
|
Romecín P, Atucha NM, Navarro EG, Ortiz MC, Iyú D, Rosado JA, García-Estañ J. Role of homocysteine and folic acid on the altered calcium homeostasis of platelets from rats with biliary cirrhosis. Platelets 2017; 28:698-705. [PMID: 28150525 DOI: 10.1080/09537104.2016.1265920] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state. Different studies indicate that cholestatic diseases are associated with hyperhomocysteinemia; thus, we hypothetized that it could contribute to those platelet alterations. In the present study, we have investigated the role of homocysteine (HCY) in platelet aggregation and calcium signaling in the BDL model. The effect of chronic folic acid treatment was also analyzed. Acute treatment with HCY increased the aggregation response to ADP and calcium responses to thrombin in platelets of control and BDL rats. Capacitative calcium entry was not altered by HCY. Chronic treatment with folic acid decreased platelet aggregation in control and BDL rats, but this decrease was greater in BDL rats. In folic acid-treated rats, thrombin-induced calcium entry and release were decreased in platelet of control rats but unaltered in BDL rats; however, capacitative calcium entry was decreased in platelets of control and BDL rats treated with folic acid. Reactive oxygen species were produced at higher levels by BDL platelets after stimulation with HCY or thrombin and folic acid normalized these responses. HCY plays a role in the enhanced platelet aggregation response of BDL rats, probably through an enhanced formation of ROS. Folic acid pretreatment normalizes many of the platelet alterations shown by BDL rats.
Collapse
Affiliation(s)
- Paola Romecín
- a Depto. Fisiología, Fac. Medicina, Instituto Murciano de Investigación Biosanitaria (IMIB) , Universidad de Murcia, Murcia, Spain
| | - Noemí M Atucha
- a Depto. Fisiología, Fac. Medicina, Instituto Murciano de Investigación Biosanitaria (IMIB) , Universidad de Murcia, Murcia, Spain
| | - Esther G Navarro
- a Depto. Fisiología, Fac. Medicina, Instituto Murciano de Investigación Biosanitaria (IMIB) , Universidad de Murcia, Murcia, Spain
| | - M Clara Ortiz
- a Depto. Fisiología, Fac. Medicina, Instituto Murciano de Investigación Biosanitaria (IMIB) , Universidad de Murcia, Murcia, Spain
| | - David Iyú
- a Depto. Fisiología, Fac. Medicina, Instituto Murciano de Investigación Biosanitaria (IMIB) , Universidad de Murcia, Murcia, Spain
| | - Juan Antonio Rosado
- b Depto. Fisiología, Fac. Veterinaria , Universidad de Extremadura , Cáceres, Spain
| | - Joaquín García-Estañ
- a Depto. Fisiología, Fac. Medicina, Instituto Murciano de Investigación Biosanitaria (IMIB) , Universidad de Murcia, Murcia, Spain
| |
Collapse
|