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1
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Raza S, Pinkerton P, Hirsh J, Callum J, Selby R. The historical origins of modern international normalized ratio targets. J Thromb Haemost 2024; 22:2184-2194. [PMID: 38795872 DOI: 10.1016/j.jtha.2024.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 05/07/2024] [Accepted: 05/15/2024] [Indexed: 05/28/2024]
Abstract
Prothrombin time (PT) and its derivative international normalized ratio (INR) are frequently ordered to assess the coagulation system. Plasma transfusion to treat incidentally abnormal PT/INR is a common practice with low biological plausibility and without credible evidence, yet INR targets appear in major clinical guidelines and account for the majority of plasma use at many institutions. In this article, we review the historical origins of INR targets. We recount historical milestones in the development of the PT, discovery of vitamin K antagonists (VKAs), motivation for INR standardization, and justification for INR targets in patients receiving VKA therapy. Next, we summarize evidence for INR testing to assess bleeding risk in patients not on VKA therapy and plasma transfusion for treating mildly abnormal INR to prevent bleeding in these patients. We conclude with a discussion of the parallels in misunderstanding of historic PT and present-day INR testing with lessons from the past that might help rationalize plasma transfusion in the future.
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Affiliation(s)
- Sheharyar Raza
- Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Canadian Blood Services, Medical Affairs and Innovation, Toronto, Ontario, Canada.
| | - Peter Pinkerton
- Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine & Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Jack Hirsh
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Jeannie Callum
- Department of Pathology and Molecular Medicine, Kingston Health Sciences Centre and Queen's University, Kingston, Kingston, Ontario, Canada
| | - Rita Selby
- Department of Laboratory Medicine & Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Laboratory Medicine Program, University Health Network, University of Toronto, Toronto, Ontario, Canada
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2
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Tripodi A, Primignani M, D'Ambrosio R, Tosetti G, La Mura V, Lampertico P, Peyvandi F. Reappraisal of the conventional hemostasis tests as predictors of perioperative bleeding in the era of rebalanced hemostasis in cirrhosis. Hepatology 2024:01515467-990000000-00718. [PMID: 38214562 DOI: 10.1097/hep.0000000000000756] [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: 09/11/2023] [Accepted: 11/24/2023] [Indexed: 01/13/2024]
Abstract
New global laboratory procedures mimicking the in vivo hemostasis process led to the changing paradigm of cirrhosis from the prototype of hemorrhagic diseases to a condition in which hemostasis is normal but fragile, thus justifying the hemorrhagic/thrombotic tendencies that affect these patients. The new paradigm was instrumental to change the management of cirrhosis. For example, international guidelines warn against the entrenched practice of testing patients with conventional hemostasis tests and infusing those with abnormalities with fresh-frozen plasma, coagulation factor concentrates, or platelets, prior to surgery/invasive procedures. These recommendations are, however, largely disattended. The practice of testing patients with the prothrombin time or viscoelastometry and using arbitrary cutoffs to make decisions on perioperative prophylaxis is still common and probably driven by medicolegal issues. There is no doubt that prothrombin time and congeners tests are unable to predict bleeding in cirrhosis. However, it cannot be excluded that some tests may be useful in patients who are severely decompensated. Large prospective collaborative studies are warranted. Enrolled patients should be randomized to receive perioperative prophylaxis based on laboratory testing (eg, viscoelastometry, thrombomodulin-modified thrombin generation) or to usual care. However, for these trials to be useful, a third group of patients who do not receive prophylaxis should be included. In conclusion, until results from these studies are available, physicians attending cirrhosis should refrain from using laboratory tests with arbitrary cutoffs to make decision on perioperative prophylaxis. Decision should be made by considering the clinical history of individual patients and the risk of hemorrhage of specific procedures.
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Affiliation(s)
- Armando Tripodi
- IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy
| | - Massimo Primignani
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Roberta D'Ambrosio
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giulia Tosetti
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Vincenzo La Mura
- IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy
| | - Pietro Lampertico
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, CRC "A. M. and A. Migliavacca" Center for Liver Disease, University of Milan, Milan, Italy
| | - Flora Peyvandi
- IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy
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3
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Scalambrino E, Faioni EM, Clerici M, Avarello I, Capecchi M, Pasca S, Tripodi A. Bilirubin color interference on prothrombin time and activated partial thromboplastin time tests assessed in patients with liver disease. Clin Chem Lab Med 2023; 61:e244-e247. [PMID: 37337903 DOI: 10.1515/cclm-2023-0393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 05/19/2023] [Indexed: 06/21/2023]
Affiliation(s)
- Erica Scalambrino
- IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
| | - Elena M Faioni
- ASST Santi Carlo e Paolo, SIMT Presidio San Paolo, Milan, Italy
- Department of Health Sciences, Università degli Studi di Milan, Milan, Italy
| | - Marigrazia Clerici
- IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
| | - Ilaria Avarello
- ASST Santi Carlo e Paolo, SIMT Presidio San Paolo, Milan, Italy
| | - Marco Capecchi
- IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
| | - Samantha Pasca
- IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
| | - Armando Tripodi
- IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
- Fondazione Luigi Villa, Milan, Italy
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4
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Wilson S, Joseph J, Danta M, Rabbolini DJ. Viscoelastometry to Manage Bleeding in Liver Disease. Cureus 2023; 15:e41401. [PMID: 37546051 PMCID: PMC10402654 DOI: 10.7759/cureus.41401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/05/2023] [Indexed: 08/08/2023] Open
Abstract
A state of "re-balanced haemostasis" describes complex coagulation changes that arise in patients with liver disease. Changes include alterations in procoagulant and anticoagulant proteins, platelets and von Willebrand factor, as well as the fibrinolytic system. Various circumstances including infection, trauma, or surgery may disrupt this balance and predispose an individual to bleeding or thrombosis. The prothrombin time, international normalised ratio, and activated partial thromboplastin time are conventional coagulation screening tests that are routinely employed by clinicians to investigate unexplained bleeding, monitor anticoagulation, and inform preoperative assessments of bleeding risk. These standard coagulation tests assess quantitative defects in procoagulant clotting factors and are insensitive to levels of natural anticoagulants, which together with procoagulant factors, are often perturbed in liver disease. Therefore, the prolongation of clotting times measured by these tests often does not reflect the multifaceted alterations of haemostasis in these patients. Viscoelastic testing (VET) provides a more encompassing assessment of clotting function by recording real-time viscoelastic changes in whole blood and includes parameters that provide information on coagulation factor function, platelet contribution to clot formation, as well as fibrinolysis. To date, VET has been employed to predict and inform transfusion support in obstetric, trauma, and cardiac surgical fields, and its use in patients undergoing liver transplantation is well established. The ability of VET to accurately predict bleeding risk and precisely guide transfusion algorithms for patients with liver disease undergoing other invasive procedures or experiencing bleeding complications has been the topic of research over the last decade. This review is a critical summary of this data and provides a detailed snapshot of the position of VET as a clinical tool in patients with liver disease.
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Affiliation(s)
- Samantha Wilson
- Gastroenterology and Hepatology, School of Clinical Medicine, St. Vincent's Healthcare Campus, Faculty of Medicine, University of New South Wales, Sydney, AUS
| | - Joanne Joseph
- Hematology, School of Clinical Medicine, St. Vincent's Healthcare Campus, Faculty of Medicine, University of New South Wales, Sydney, AUS
- Hematology, St. Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, AUS
| | - Mark Danta
- Gastroenterology and Hepatology, School of Clinical Medicine, St. Vincent's Healthcare Campus, Faculty of Medicine, University of New South Wales, Sydney, AUS
- Gastroenterology and Hepatology, St. Vincent's Hospital, Sydney, AUS
| | - David J Rabbolini
- Faculty of Medicine and Health, University of Sydney, Sydney, AUS
- Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, GBR
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5
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Rautou PE, Caldwell SH, Villa E. Bleeding and Thrombotic Complications in Patients With Cirrhosis: A State-of-the-Art Appraisal. Clin Gastroenterol Hepatol 2023; 21:2110-2123. [PMID: 37121529 DOI: 10.1016/j.cgh.2023.04.016] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 04/02/2023] [Accepted: 04/14/2023] [Indexed: 05/02/2023]
Abstract
Much has evolved over the past 25 years regarding our understanding of the coagulopathy of liver disease. Paradoxically, this form of coagulopathy is relatively hypercoagulability despite the common clinical impression of a hemorrhagic tendency. The latter is largely driven by portal-mesenteric venous pressure (ie, portal hypertension) and has little to do with hemostatic pathways. It cannot be emphasized enough that the INR does not offer a meaningful measure in this situation and may lead to interventions such as fresh frozen plasma that can actually worsen portal pressure and hence pressure-driven bleeding. With regard to procedure-related bleeding, we point out substantial differences in the definition of high-risk procedures and propose a new operational definition dependent on the applicability of local hemostatic measures, although this requires further investigation. The common occurrence of venous thrombosis in these patients requires careful consideration of hemostatic pathways and overall risk and benefit of intervention. The decision regarding anticoagulation therapy needs to be driven not only by a global assessment including history of non-portal hypertensive-related bleeding, but also by fall risk which can result in head trauma in patients prone to encephalopathy. This is probably best estimated by frailty but has yet to be adequately investigated. In the background of these concerns, several superimposed and complex conditions including infections and renal dysfunction should be taken into account. Inherited forms of thrombophilia in the setting of cirrhosis perhaps do not outweigh the thrombophilia inherent to liver disease but warrant further consideration.
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Affiliation(s)
- Pierre-Emmanuel Rautou
- Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France; Service d'Hépatologie, AP-HP, Hôpital Beaujon, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - Stephen H Caldwell
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Virginia, Charlottesville, Virginia.
| | - Erica Villa
- Gastroenterology Unit, CHIMOMO Department, University of Modena and Reggio Emilia, Modena, Italy; IRCCS Saverio de Bellis, Castellana Grotte, Italy
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6
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Schaefer JK, Fontana RJ. Hematohepatology: The potential for direct oral anticoagulant "Inflation" in liver transplant candidates. Res Pract Thromb Haemost 2023; 7:100082. [PMID: 36908767 PMCID: PMC9999199 DOI: 10.1016/j.rpth.2023.100082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 01/30/2023] [Indexed: 02/17/2023] Open
Affiliation(s)
- Jordan K Schaefer
- Department of Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan, USA
| | - Robert J Fontana
- Department of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
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7
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Latona A, Hill K, Connelly A, Stuart K, Wood P. Prothrombinex®-VF in chronic liver disease: Friend or foe? Emerg Med Australas 2023; 35:89-96. [PMID: 35993256 PMCID: PMC10087488 DOI: 10.1111/1742-6723.14058] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 05/11/2022] [Accepted: 07/28/2022] [Indexed: 01/19/2023]
Abstract
OBJECTIVE Management of coagulopathy in chronic liver disease (CLD) poses a challenge for critical care physicians. Prothrombinex®-VF is a low-volume product with rapid onset of action. Evidence for its efficacy and safety in CLD is limited and cases of acute intravascular coagulation and fibrinolysis (AICF) and/or disseminated intravascular coagulation (DIC) have been reported. Our objective was to evaluate the role of Prothrombinex®-VF in reversal of coagulopathy and the incidence AICF/DIC, thromboembolic events and mortality. METHODS This was a retrospective, multi-centre study of Prothrombinex®-VF use in CLD across 11 hospitals over a 2-year period, excluding those on therapeutic anticoagulation. Patients were subclassified into acute on chronic liver failure (ACLF), acute decompensation (ADC) and compensated cirrhosis. Reversal of coagulopathy was defined as international normalised ratio (INR) <1.5× upper limit normal (ULN), prothrombin time <1.5× ULN, activated partial thromboplastin time <1.5× ULN and fibrinogen >1 g/L. Markers of AICF/DIC were recorded. RESULTS Thirty CLD patients were included, and the median model for end-stage liver disease score was 23.5. Acute bleeding was the most common indication for Prothrombinex®-VF (60%). All had baseline coagulopathy and the majority did not achieve reversal. Key indicators of AICF/DIC were mainly observed in those with ACLF; bleeding from mucosa or lines (53%), worsening hypofibrinogenaemia (60%), worsening thrombocytopaenia (60%). The ADC and compensated cirrhosis groups were relatively unaffected. Incidence of venous thromboembolism was 6%. Overall mortality was 43% and 70% in ACLF. CONCLUSION Prothrombinex®-VF did not lead to meaningful reversal of coagulopathy and should be used with caution in CLD. Patients with ACLF were more likely to develop AICF/DIC following Prothrombinex®-VF, although the association is uncertain. Further studies are needed to evaluate the safety and efficacy of Prothrombinex®-VF use in CLD.
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Affiliation(s)
- Akmez Latona
- Department of Emergency Medicine, Ipswich Hospital, Ipswich, Queensland, Australia.,Department of Emergency Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Department of Emergency Medicine, St Vincent's Private Hospital, Toowoomba, Queensland, Australia.,The University of Queensland, Brisbane, Queensland, Australia
| | - Kate Hill
- Department of Haematology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Griffith University, Brisbane, Queensland, Australia
| | - Aurelia Connelly
- Department of Emergency Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Katherine Stuart
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Peter Wood
- Department of Haematology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.,Department of Haematology, Calderdale and Huddersfield NHS Foundation Trust, Huddersfield, England
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8
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MELD 3.0 Score for Predicting Survival in Patients with Cirrhosis After Transjugular Intrahepatic Portosystemic Shunt Creation. Dig Dis Sci 2023:10.1007/s10620-023-07834-3. [PMID: 36715817 DOI: 10.1007/s10620-023-07834-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Accepted: 01/09/2023] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND AIMS The selection of appropriate candidates for transjugular intrahepatic portosystemic shunt (TIPS) is important and challenging. To validate the Model for End-Stage Liver Disease (MELD) 3.0 in predicting mortality in patients with cirrhosis after TIPS creation. METHODS A total of 855 consecutive patients with cirrhosis from December 2011 to October 2019 who underwent TIPS placement were retrospectively reviewed. The prognostic value of the MELD 3.0, MELD, MELD-Na, Child-Pugh and FIPS score was assessed using Harrell's C concordance index (c-index). The Hosmer-Lemeshow test was used to test the goodness of fit of all models and the calibration plot was drawn. RESULTS The c-index of the MELD 3.0 in predicting 3-month mortality was 0.727 (0.645-0.808), which were significantly superior to the MELD (0.663 [0.565-0.761]; P = 0.015), MELD-Na (0.672 [0.577-0.768]; P = 0.008) and FIPS (0.582 [0.477-0.687]; P = 0.015). The Child-Pugh score reached c-indices of 0.754 (0.673-0.835), 0.720 (0.649-0.792), 0.705 (0.643-0.766) and 0.665 (0.614-0.716) for 3-month, 6-month, 1-year, and 2-year mortality, respectively, which seems comparable to MELD 3.0. A MELD 3.0 of 14 could be used as a cut-off point for discriminating between high- and low-risk patients. The MELD 3.0 could stratify patients with Child-Pugh grade B (log-rank P < 0.001). The Child-Pugh score could stratify patients defined as low risk by MELD 3.0 (log-rank P < 0.001). CONCLUSIONS The MELD 3.0 was significantly superior to the MELD, MELD-Na and FIPS scores in predicting mortality in patients with cirrhosis after TIPS creation.
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9
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Luo Y, Cuneo KC, Lawrence TS, Matuszak MM, Dawson LA, Niraula D, Ten Haken RK, El Naqa I. A human-in-the-loop based Bayesian network approach to improve imbalanced radiation outcomes prediction for hepatocellular cancer patients with stereotactic body radiotherapy. Front Oncol 2022; 12:1061024. [PMID: 36568208 PMCID: PMC9782976 DOI: 10.3389/fonc.2022.1061024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 11/01/2022] [Indexed: 12/13/2022] Open
Abstract
Background Imbalanced outcome is one of common characteristics of oncology datasets. Current machine learning approaches have limitation in learning from such datasets. Here, we propose to resolve this problem by utilizing a human-in-the-loop (HITL) approach, which we hypothesize will also lead to more accurate and explainable outcome prediction models. Methods A total of 119 HCC patients with 163 tumors were used in the study. 81 patients with 104 tumors from the University of Michigan Hospital treated with SBRT were considered as a discovery dataset for radiation outcomes model building. The external testing dataset included 59 tumors from 38 patients with SBRT from Princess Margaret Hospital. In the discovery dataset, 100 tumors from 77 patients had local control (LC) (96% of 104 tumors) and 23 patients had at least one grade increment of ALBI (I-ALBI) during six-month follow up (28% of 81 patients). Each patient had a total of 110 features, where 15 or 20 features were identified by physicians as expert knowledge features (EKFs) for LC or I-ALBI prediction. We proposed a HITL based Bayesian network (HITL-BN) approach to enhance the capability of selecting important features from imbalanced data in terms of accuracy and explainability through humans' participation by integrating feature importance ranking and Markov blanket algorithms. A pure data-driven Bayesian network (PD-BN) method was applied to the same discovery dataset of HCC patients as a benchmark. Results In the training and testing phases, the areas under receiver operating characteristic curves of the HITL-BN models for LC or I-ALBI prediction during SBRT are 0.85 (95% confidence interval: 0.75-0.95) or 0.89 (0.81-0.95) and 0.77 or 0.78, respectively. They significantly outperformed the during-treatment PD-BN model in predicting LC or I-ALBI based on the discovery cross-validation and testing datasets from the Delong tests. Conclusion By allowing the human expert to be part of the model building process, the HITL-BN approach yielded significantly improved accuracy as well as better explainability when dealing with imbalanced outcomes in the prediction of post-SBRT treatment response of HCC patients when compared to the PD-BN method.
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Affiliation(s)
- Yi Luo
- Department of Machine Learning, Moffitt Cancer Center, Tampa, FL, United States,*Correspondence: Yi Luo,
| | - Kyle C. Cuneo
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States
| | - Theodore S. Lawrence
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States
| | - Martha M. Matuszak
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States
| | - Laura A. Dawson
- Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - Dipesh Niraula
- Department of Machine Learning, Moffitt Cancer Center, Tampa, FL, United States
| | - Randall K. Ten Haken
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States
| | - Issam El Naqa
- Department of Machine Learning, Moffitt Cancer Center, Tampa, FL, United States
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10
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Validating the prognostic value of Freiburg index of posttransjugular intrahepatic portosystemic shunt survival score and classic scores in Chinese patients with implantation of transjugular intrahepatic portosystemic shunt. Eur J Gastroenterol Hepatol 2022; 34:1074-1080. [PMID: 36062497 DOI: 10.1097/meg.0000000000002427] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND AIMS It is important and challenging to evaluate the survival of cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). We aimed to validate the Freiburg index of post-TIPS survival (FIPS) score and classic scores for predicting mortality in Chinese patients after TIPS creation. METHODS A total of 709 consecutive patients with cirrhosis from December 2011 to July 2018 who underwent TIPS placement were retrospectively reviewed. The prognostic value of the FIPS score, the model for end-stage liver disease (MELD) score, Child-Pugh score and Chronic Liver Failure Consortium Acute Decompensation score was validated with the receiver operating characteristic (ROC) curve and DeLong et al. test. RESULTS The MELD-Na score was superior to the FIPS score in predicting 1-month mortality [AUROC, 0.727 (0.692-0.759) vs. 0.588 (0.551-0.625); P = 0.048]. The MELD and MELD-Na scores were significant superior to the FIPS score in predicting 3-month mortality [AUROC, 0.730 (0.696-0.762) vs. 0.598 (0.561-0.634); P = 0.044 and 0.740 (0.706-0.772) vs. 0.598 (0.561-0.634); P = 0.028]. Subgroup analyses revealed that Child-Pugh score was better than FIPS score in predicting 3-month mortality [AUROC, 0.797 (0.745-0.843) vs. 0.578 (0.517-0.637); P = 0.049] in nonviral cirrhosis group. CONCLUSION Classic scores still had good risk stratification and predictive ability of post-TIPS mortality. The FIPS score was not superior to the classic scores in the current Chinese cohort. The MELD and MELD-Na scores were significantly superior to the FIPS score in predicting 3-month mortality.
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11
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Primignani M, Tosetti G. Quantification of exceedingly high levels of von Willebrand factor in cirrhosis: Next upgrading of the MELD-Na score? Dig Liver Dis 2022; 54:1374-1375. [PMID: 35906164 DOI: 10.1016/j.dld.2022.07.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 07/11/2022] [Indexed: 12/29/2022]
Affiliation(s)
- Massimo Primignani
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy.
| | - Giulia Tosetti
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
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12
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Shettar SS, Vandyck K, Tanaka KA. Coagulation Management in End-Stage Liver Disease. CURRENT ANESTHESIOLOGY REPORTS 2022. [DOI: 10.1007/s40140-022-00524-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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13
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Primignani M, Tripodi A. Antithrombotic Therapy and Liver Disease. VASCULAR DISORDERS OF THE LIVER 2022:249-265. [DOI: 10.1007/978-3-030-82988-9_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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14
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Su F, Northup PG. Anticoagulants and Antiplatelet Agents in Cirrhosis. PHARMACOTHERAPY FOR LIVER CIRRHOSIS AND ITS COMPLICATIONS 2022:23-48. [DOI: 10.1007/978-981-19-2615-0_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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15
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Tanaka KA, Shettar S, Vandyck K, Shea SM, Abuelkasem E. Roles of Four-Factor Prothrombin Complex Concentrate in the Management of Critical Bleeding. Transfus Med Rev 2021; 35:96-103. [PMID: 34551881 DOI: 10.1016/j.tmrv.2021.06.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 06/27/2021] [Indexed: 12/19/2022]
Abstract
Four-factor prothrombin complex concentrate (4F-PCC) is the term used to describe a pathogen-reduced, lyophilized concentrate that contains therapeutic amounts of at least 4 coagulation factors: Factor II (FII), Factor VII (FVII), Factor IX (FIX), and Factor X (FX). 4F-PCC has proven to be an effective hemostatic agent compared to plasma transfusion in several prospective randomized trials in acute warfarin reversal. In recent years, 4F-PCC has been used in various acquired coagulopathies including post-cardiopulmonary bypass bleeding, trauma-induced coagulopathy, coagulopathy in liver failure, and major bleeding due to anti-FXa (anti-Xa) inhibitors (eg, rivaroxaban and apixaban). As transfusion of frozen plasma (FP) has not been found efficacious in the above critical bleeding scenarios, there is increasing interest in expanding the use of 4F-PCC. However, efficacy, safety, and clinical implications of expanded use of 4F-PCC have not been fully elucidated. Prothrombin time and international normalized ratio are commonly used to assess dose effects of 4F-PCC. Prothrombin time/international normalized ratio are standardly use for warfarin titration, but they are not suited for real-time monitoring of complex coagulopathies. Optimal dosing of 4F-PCC outside of the current approved use for vitamin K antagonist reversal is yet to be determined. In this review, we will discuss the use of 4F-PCC in four critical bleeding settings: cardiac surgery, major trauma, end-stage liver disease, and oral anti-Xa reversal. We will discuss recent studies in each area to explore the dosing, efficacy, and safety of 4F-PCC.
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Affiliation(s)
- Kenichi A Tanaka
- Department of Anesthesiology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA.
| | - Shashank Shettar
- Department of Anesthesiology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA
| | - Kofi Vandyck
- Department of Anesthesiology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA
| | - Susan M Shea
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
| | - Ezeldeen Abuelkasem
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA, USA
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Experiences from six years of quality assured Model of End Stage Liver Disease (MELD) diagnostics. PLoS One 2021; 16:e0254219. [PMID: 34437537 PMCID: PMC8389365 DOI: 10.1371/journal.pone.0254219] [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] [Received: 11/01/2020] [Accepted: 06/22/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The model of end-stage liver disease (MELD) score was established for the allocation of liver transplants. The score is based on the medical laboratory parameters: bilirubin, creatinine and the international normalized ratio (INR). A verification algorithm for the laboratory MELD diagnostic was established, and the results from the first six years were analyzed. METHODS We systematically investigated the validity of 7,270 MELD scores during a six-year period. The MELD score was electronically requested by the clinical physician using the laboratory system and calculated and specifically validated by the laboratory physician in the context of previous and additional diagnostics. RESULTS In 2.7% (193 of 7,270) of the cases, MELD diagnostics did not fulfill the specified quality criteria. After consultation with the sender, 2.0% (145) of the MELD scores remained invalid for different reasons and could not be reported to the transplant organization. No cases of deliberate misreporting were identified. In 34 cases the dialysis status had to be corrected and there were 24 cases of oral anticoagulation with impact on MELD diagnostics. CONCLUSION Our verification algorithm for MELD diagnostics effectively prevented invalid MELD results and could be adopted by transplant centers to prevent diagnostic errors with possible adverse effects on organ allocation.
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Piñero F, da Fonseca LG. Trial eligibility in advanced hepatocellular carcinoma: Does it support clinical practice in underrepresented subgroups? World J Gastroenterol 2021; 27:3429-3439. [PMID: 34239261 PMCID: PMC8240059 DOI: 10.3748/wjg.v27.i24.3429] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/06/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
Although hepatocellular carcinoma is considered a highly lethal malignancy, recent therapeutic advances have been achieved during the last 10 years. This scenario resulted in an unprecedented improvement in survival for patients with advanced hepatocellular carcinoma, almost reaching 20-26 mo of overall survival after first-second line sequential treatment. The advent of the combination of atezolizumab with bevacizumab showed, for the first time, superiority over sorafenib with improvement in overall survival. However, first and second-line trials were correctly based on the premise that a strict selection of patients enhances the power to capture the positive effect of treatment by excluding competing risks for mortality such as liver failure, decompensated cirrhosis or other underlying medical conditions. As a result, the inclusion criteria used in clinical trials do not support the use of novel therapies in several real-world scenarios involving underrepresented subgroups, such as patients with unpreserved liver function, other comorbid conditions, a history of solid-organ transplantation, autoimmune disorders and those with a high risk of bleeding. The present text aims at discussing treatment strategies in these subgroups.
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Affiliation(s)
- Federico Piñero
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, Buenos Aires B1629HJ, Argentina
| | - Leonardo Gomes da Fonseca
- Clinical Oncology, Insituto do Cancer do Estado de São Paulo, University of São Paulo, São Paulo 05403-000, Brazil
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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: 01/28/2021] [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.
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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
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Zhang T, Wei Y, He X, Yuan Y, Yuan F, Ye Z, Li X, Tang H, Song B. Prediction of Remnant Liver Regeneration after Right Hepatectomy in Patients with Hepatocellular Carcinoma Using Preoperative CT Texture Analysis and Clinical Features. CONTRAST MEDIA & MOLECULAR IMAGING 2021; 2021:5572470. [PMID: 34220379 PMCID: PMC8213498 DOI: 10.1155/2021/5572470] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 05/28/2021] [Accepted: 06/02/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVES To predict the regenerative rate of liver in patients with HCCs after right hepatectomy using texture analysis on preoperative CT combined with clinical features. MATERIALS AND METHODS 88 patients with 90 HCCs who underwent right hepatectomy were retrospectively included. The future remnant liver was semiautomatically segmented, and the volume of future remnant liver on preoperative CT (LVpre) and the volume of remnant liver on following-up CT (LVfu) were measured. We calculated the regeneration index (RI) by the following equation: (LVfu - LVpre)/LVpre) × 100 (%). The support vector machine recursive method was used for the feature selection. The Naive Bayes classifier was used to predict liver RI, and 5-fold cross-validation was performed to adjust the parameters. Sensitivity, specificity, and accuracy were calculated to evaluate the diagnostic efficiency of the model. RESULTS The mean RI was 142.99 ± 92.17%. Of all clinical parameters and texture features, the AST, ALB, PT-INR, Perc.10%, and S(5, -5)Correlat were found to be statistically significant with RI. The diagnostic sensitivity, specificity, and accuracy of the model in the training group were 0.902, 0.634, and 0.768, and the AUC value of the obtained model was 0.841. In the test group, the sensitivity, specificity, and accuracy of the model were 1.0, 0.429, and 0.778, respectively, and the AUC value was 0.844. CONCLUSION The use of texture analysis on preoperative CT combined with clinical features can be helpful in predicting the liver regeneration rate in patients with HCCs after right hepatectomy.
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Affiliation(s)
- Tong Zhang
- Department of Radiology, Sichuan University West China Hospital, Chengdu 610041, Sichuan Province, China
| | - Yi Wei
- Department of Radiology, Sichuan University West China Hospital, Chengdu 610041, Sichuan Province, China
| | - Xiaopeng He
- Department of Radiology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Yuan Yuan
- Department of Radiology, Sichuan University West China Hospital, Chengdu 610041, Sichuan Province, China
| | - Fang Yuan
- Department of Radiology, Sichuan University West China Hospital, Chengdu 610041, Sichuan Province, China
| | - Zheng Ye
- Department of Radiology, Sichuan University West China Hospital, Chengdu 610041, Sichuan Province, China
| | - Xin Li
- GE Healthcare Research, Nanjing 210000, China
| | - Hehan Tang
- Department of Radiology, Sichuan University West China Hospital, Chengdu 610041, Sichuan Province, China
| | - Bin Song
- Department of Radiology, Sichuan University West China Hospital, Chengdu 610041, Sichuan Province, China
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Carta M, Bonente F, Teresa Comberlato M, Pellizzari T, Marotto E, Marzari E, Giavarina D. Evaluation of STA-NeoPTimal, an extraction thromboplastin reagent with ISI close to 1. Int J Lab Hematol 2020; 43:311-317. [PMID: 33070473 DOI: 10.1111/ijlh.13365] [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: 07/03/2020] [Revised: 09/14/2020] [Accepted: 09/21/2020] [Indexed: 11/28/2022]
Abstract
INTRODUCTION The prothrombin time (PT) is the most requested test to investigate patients with congenital or acquired coagulopathies or to monitor oral anticoagulant therapy. However, thromboplastins can show markedly different responsiveness to the defects induced by vitamin K antagonist (VKA) therapy and are thus characterized by their ISI (International Sensitivity Index). INR results are optimal for patients under VKA but for patients screened for other reasons expressing PT results as ratio can be more appropriate. As it is very difficult to define the PT results reporting unit from the PT testing request, it would be ideal to use a thromboplastin with ISI = 1. The study aims to compare our reference PT reagent with two candidate thromboplastins with ISI close to 1. METHODS We compared 3 different thromplastins: two rabbit brain extracted based reagents (STA-Neoplastine CI Plus, with ISI = 1.26, routinely used in our laboratory and STA-NeoPTimal with ISI = 1.01) and a recombinant thromboplastin (STA-Neoplastine R with ISI = 0.97). The comparison was done on 175 samples: 75 from individuals without coagulation defects and 100 from patients under VKA. RESULTS STA-NeoPTimal and STA-Neoplastine R well correlate to our reference, STA-Neoplastine CI Plus: regression equations are y = 1.186x-0.1351, r2 = .9454 and y = 1.1432x-0.1554, r2 = .9951, respectively. The lowest bias on INR results was obtained with STA-NeoPTimal reagent (interval: -0.7/+0.4). CONCLUSION We conclude that STA-NeoPTimal can be used in the laboratory as it gives results comparable to those obtained with STA-Neoplastine CI Plus. Besides, thanks to its ISI = 1, it guarantees reporting a PT ratio equal to INR which avoids errors.
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Affiliation(s)
| | - Francesca Bonente
- AULSS 9 Scaligera, Laboratorio di Analisi chimico-cliniche e Microbiologia, San Bonifacio, Italy
| | | | | | - Elena Marotto
- AULSS 8 Berica, Medicina di Laboratorio, Vicenza, Italy
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21
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Dorgalaleh A, Favaloro EJ, Bahraini M, Rad F. Standardization of Prothrombin Time/International Normalized Ratio (PT/INR). Int J Lab Hematol 2020; 43:21-28. [PMID: 32979036 DOI: 10.1111/ijlh.13349] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 09/02/2020] [Accepted: 09/07/2020] [Indexed: 01/02/2023]
Abstract
The prothrombin time (PT) represents the most commonly used coagulation test in clinical laboratories. The PT is mathematically converted to the international normalized ratio (INR) for use in monitoring anticoagulant therapy with vitamin K antagonists such as warfarin in order to provide test results that are adjusted for thromboplastin and instrument used. The INR is created using two major PT 'correction factors', namely the mean normal PT (MNPT) and the international sensitivity index (ISI). Manufacturers of reagents and coagulometers have made some efforts to harmonizing INRs, for example, by tailoring reagents to specific coagulometers and provide associated ISI values. Thus, two types of ISIs may be generated, with one being a 'general' or 'generic' ISI and others being reagent/coagulometer-specific ISI values. Although these play a crucial role in improving INR results between laboratories, these laboratories reported INR values are known to still differ, even when laboratories use the same thromboplastin reagent and coagulometer. Moreover, ISI values for a specific thromboplastin can vary among different models of coagulometers from a manufacturer using the same method for clot identification. All these factors can be sources of error for INR reporting, which in turn can significantly affect patient management. In this narrative review, we provide some guidance to appropriate ISI verification/validation, which may help decrease the variability in cross laboratory reporting of INRs.
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Affiliation(s)
- Akbar Dorgalaleh
- Department of Hematology and Blood Transfusion, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Emmanuel J Favaloro
- Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia
| | - Mehran Bahraini
- Department of Hematology and Blood Transfusion, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Fariba Rad
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.,Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
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Ollivier-Hourmand I, Nguyen N, De Gottardi A, Valla D, Hillaire S, Dutheil D, Bureau C, Hernandez-Gea V, De Raucourt E, Plessier A. Management of anticoagulation in adult patients with chronic parenchymal or vascular liver disease: Vascular liver diseases: Position papers from the francophone network for vascular liver diseases, the French Association for the Study of the Liver (AFEF), and ERN-rare liver. Clin Res Hepatol Gastroenterol 2020; 44:438-446. [PMID: 32278777 DOI: 10.1016/j.clinre.2020.03.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 03/03/2020] [Indexed: 02/04/2023]
Affiliation(s)
- Isabelle Ollivier-Hourmand
- Department of gastroenterology and hepatology, university hospital of Caen, Côte de la Nacre hospital, avenue de la Côte de Nacre, 14033 Caen cedex 9, France; French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France.
| | - Nga Nguyen
- Department of gastroenterology and hepatology, university hospital of Caen, Côte de la Nacre hospital, avenue de la Côte de Nacre, 14033 Caen cedex 9, France; French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France
| | - Andrea De Gottardi
- Department of gastroenterology and hepatology, Cantonal Hospital Authority, Direzione generale, Viale Officina 3, 6500 Bellinzona, Switzerland
| | - Dominique Valla
- French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of hepatology, Beaujon hospital AP-HP, 100, boulevard du Général Leclerc, 92118 Clichy, France; Reference center of vascular liver diseases, European Reference Network (ERN) "Rare-Liver", Clichy, France
| | - Sophie Hillaire
- Department of internal medicine, Foch hospital, 40, rue Worth, 92150 Suresnes, France
| | - Danielle Dutheil
- French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of hepatology, Association of patients with vascular liver diseases (AMVF), Beaujon hospital, 100, boulevard du Général Leclerc, 92118 Clichy, France
| | - Christophe Bureau
- French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of gastroenterology and hepatology, university hospital of Toulouse, Rangueil hospital, 1, avenue du Professeur Jean-Poulhès, 31400 Toulouse, France
| | - Virginia Hernandez-Gea
- Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona. Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd). Health Care Provider of the European Reference Network onRare Liver Disorders (ERN-Liver), Spain
| | - Emmanuelle De Raucourt
- French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of laboratory hematology, Beaujon hospital AP-HP, 100, boulevard du Général Leclerc, 92118 Clichy, France; Reference center of vascular liver diseases, European Reference Network (ERN) "Rare-Liver", Clichy, France
| | - Aurélie Plessier
- French Network for Rare Liver Diseases (FILFOIE), Saint-Antoine hospital, AP-HP, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France; Department of hepatology, Beaujon hospital AP-HP, 100, boulevard du Général Leclerc, 92118 Clichy, France; Reference center of vascular liver diseases, European Reference Network (ERN) "Rare-Liver", Clichy, France
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Mullier F, Paridaens M, Evrard J, Baudar J, Guldenpfennig M, Devroye C, Miller L, Chatelain B, Lessire S, Jacqmin H. Evaluation of a new thromboplastin reagent STA‐NeoPTimal on a STA R Max analyzer for the measurement of prothrombin time, international normalized ratio and extrinsic factor levels. Int J Lab Hematol 2020; 42:650-660. [DOI: 10.1111/ijlh.13236] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 04/17/2020] [Accepted: 04/21/2020] [Indexed: 11/28/2022]
Affiliation(s)
- François Mullier
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | | | | | - Justine Baudar
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | - Maité Guldenpfennig
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | - Celia Devroye
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | - Laurence Miller
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | - Bernard Chatelain
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | - Sarah Lessire
- Department of Anesthesiology Université catholique de LouvainCHU UCL NamurNamur Thrombosis and Hemostasis Center (NTHC)Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
| | - Hugues Jacqmin
- Department of Laboratory Medicine Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for Life Sciences (NARILIS) Yvoir Belgium
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Abstract
Disorders of the mesenteric, portal, and hepatic veins and mesenteric and hepatic arteries have important clinical consequences and may lead to acute liver failure, chronic liver disease, noncirrhotic portal hypertension, cirrhosis, and hepatocellular carcinoma. Although literature in the field of vascular liver disorders is scant, these disorders are common in clinical practice, and general practitioners, gastroenterologists, and hepatologists may benefit from expert guidance and recommendations for management of these conditions. These guidelines represent the official practice recommendations of the American College of Gastroenterology. Key concept statements based on author expert opinion and review of literature and specific recommendations based on PICO/GRADE analysis have been developed to aid in the management of vascular liver disorders. These recommendations and guidelines should be tailored to individual patients and circumstances in routine clinical practice.
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Rudasill SE, Dipardo B, Sanaiha Y, Mardock AL, Cale M, Antonios JW, Benharash P. International Normalized Ratio (INR) is Comparable to MELD in Predicting Mortality after Cholecystectomy. Am Surg 2019. [DOI: 10.1177/000313481908501024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Guidelines suggest targeting a preoperative international normalized ratio (INR) < 1.5. We examined and compared the predictive value of INR relative to the Model for End-Stage Liver Disease (MELD). We reviewed the American College of Surgeons NSQIP from 2005 to 2016 for adult patients undergoing open or laparoscopic cholecystectomy. Patients with a preoperative INR were stratified into groups: ≤1, >1 to ≤1.5, >1.5 to ≤2, and >2. Thirty day postoperative mortality was the primary outcome. Multivariable logistic regressions controlled for baseline differences. Of 58,177 cholecystectomy patients, 15.2 per cent had INR ≤ 1,80.4 per cent had INR > 1 to ≤1.5,3.7 per cent had INR > 1.5 to ≤2, and 0.7 per cent had INR > 2. Patients with INR > 2 were older and more likely to have diabetes and hypertension ( P < 0.001). Multivariable regression demonstrated a stepwise increase in mortality for INR > 1 to ≤1.5 (odds ratio (OR) = 1.50 [1.10–2.05]), INR > 1.5 to ≤2 (OR = 2.96 [1.97–4.45]), and INR > 2 (OR = 3.21 [1.64–6.31]) relative to INR ≤ 1. C-statistic for INR (0.910) and MELD (0.906) models indicated a similar value in predicting mortality. INR groups also faced an incremental, increased risk of bleeding. Although unable to track preoperative correction of INR, this analysis identifies that INR remains an excellent predictor of postoperative mortality and bleeding after both open and laparoscopic cholecystectomies and is comparable to MELD.
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Affiliation(s)
- Sarah E. Rudasill
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Benjamin Dipardo
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Yas Sanaiha
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Alexandra L. Mardock
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Mario Cale
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - James W. Antonios
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Peyman Benharash
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
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Pastori D, Lip GYH, Farcomeni A, Del Sole F, Sciacqua A, Perticone F, Marcucci R, Grifoni E, Pignatelli P, Violi F. Incidence of bleeding in patients with atrial fibrillation and advanced liver fibrosis on treatment with vitamin K or non-vitamin K antagonist oral anticoagulants. Int J Cardiol 2019; 264:58-63. [PMID: 29776574 DOI: 10.1016/j.ijcard.2018.01.097] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Revised: 01/09/2018] [Accepted: 01/22/2018] [Indexed: 12/26/2022]
Abstract
OBJECTIVES To investigate the incidence of bleeding events in atrial fibrillation (AF) patients treated with vitamin K (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) screened for the presence of liver fibrosis (LF). BACKGROUND Previous studies provided conflicting results on bleeding risk in AF patients with liver disease on VKAs, and no data on NOACs in this setting are available. METHODS Post-hoc analysis of a prospective, observational multicentre study including 2330 AF outpatients treated with VKAs (n = 1297) or NOACs (n = 1033). Liver damage was quantified by the FIB-4 score (>3.25), a validated marker of LF. The primary endpoint was the incidence of any bleeding, according to ISTH classification. RESULTS A high FIB-4 was present in 129 (5.5%) patients: 77 (5.9%) on VKA and 52 (5.0%) on NOACs (p = 0.344). During follow-up, 357 (15.3%) patients experienced a bleeding: 261 (80 major and 180 minor) with VKAs (7.2%/year), and 96 (40 major and 56 minor) with NOACs (6.4%/year). In VKA-treated patients, but not in those on NOACs, FIB-4 >3.25 was associated with higher major bleeding (14.3% vs. 5.6%, log-rank test p < 0.001). Multivariable Cox regression model showed that FIB-4 was associated with major bleeding only in VKA-treated patients (HR: 3.075, 95% CI 1.626-5.818, p = 0.001). On multivariable analysis, FIB-4 was not significantly associated with CVEs neither in VKA or NOAC-treated patients. CONCLUSION We found a significant association between LF and major bleedings in AF patients treated with VKA, which was not evident in patients on NOACs.
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Affiliation(s)
- Daniele Pastori
- I Clinica Medica, Atherothrombosis Centre, Department of Internal Medicine and Medical Specialties of Sapienza University of Rome, Rome, Italy; Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Gregory Y H Lip
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Alessio Farcomeni
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Francesco Del Sole
- I Clinica Medica, Atherothrombosis Centre, Department of Internal Medicine and Medical Specialties of Sapienza University of Rome, Rome, Italy
| | - Angela Sciacqua
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy
| | - Francesco Perticone
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy
| | - Rossella Marcucci
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Elisa Grifoni
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Pasquale Pignatelli
- I Clinica Medica, Atherothrombosis Centre, Department of Internal Medicine and Medical Specialties of Sapienza University of Rome, Rome, Italy
| | - Francesco Violi
- I Clinica Medica, Atherothrombosis Centre, Department of Internal Medicine and Medical Specialties of Sapienza University of Rome, Rome, Italy.
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Ning Q. Main Complications of AECHB and Severe Hepatitis B (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498917 DOI: 10.1007/978-94-024-1603-9_2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Qin Ning
- Department of Infectious Disease, Tongji Hospital, Wuhan, China
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28
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Hypoalbuminemia is Associated With Significantly Higher Liver Transplant Waitlist Mortality and Lower Probability of Receiving Liver Transplant. J Clin Gastroenterol 2018; 52:913-917. [PMID: 29356783 DOI: 10.1097/mcg.0000000000000984] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
GOALS To evaluate the predictive value of hypoalbuminemia on liver transplant (LT) waitlist survival and probability of receiving LT among adults with end-stage liver disease (ESLD). BACKGROUND Growing evidence reports on the negative prognostic value of hypoalbuminemia among ESLD patients awaiting LT. METHODS Using 2003 to 2015 United Network for Organ Sharing data, we retrospectively evaluated the impact of mild-moderate (2.5 to 3.4 g/dL) and severe hypoalbuminemia (<2.5 g/dL) on waitlist survival and probability of receiving LT among US adults awaiting LT. Outcomes were stratified by liver disease etiology and presence of hepatocellular carcinoma (HCC), and evaluated using Kaplan-Meier and multivariate Cox proportional hazards models. RESULTS Among 128,450 adults listed for LT, 27.1% had normal albumin (≥3.5 g/dL), 53.7% mild-moderate hypoalbuminemia (2.5 to 3.4 g/dL), and 19.2% severe hypoalbuminemia (<2.5 g/dL) at time of listing. Patients with severe hypoalbuminemia had significantly lower 1-year waitlist survival compared with those with normal albumin (80.4% vs. 95.2%; P<0.001). On multivariate regression, severity of hypoalbuminemia was associated with increasing waitlist mortality, even after correcting for model for end stage liver disease-sodium and HCC [albumin, 2.5 to 3.4 g/dL: hazard ratio (HR), 1.81; 95% confidence interval (CI), 1.62-2.01; P<0.001; <2.5 g/dL: HR, 2.46; 95% CI, 2.20-2.76; P<0.001]. Patients with hypoalbuminemia had significantly lower probability of receiving LT compared with those with normal albumin (albumin <2.5 g/dL: HR, 0.80; 95% CI, 0.78-0.83; P<0.001). CONCLUSIONS ESLD patients with hypoalbuminemia have lower probability of LT despite significantly higher waitlist mortality compared with patients with normal albumin. If validated by further studies, incorporation of albumin into prognostication systems may improve the performance of US donor organ allocation systems.
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Abstract
Background and Objectives Hepatic encephalopathy (HE) research has long been impeded by the vague definition of this disabling complication of liver failure. This article provides an overview of the etiology and impact of HE on neuromuscular functions as well as its role in the development of infections and anemia. Materials and Methods This was a descriptive study conducted in 36 patients with HE. Close monitoring of these patients was done by checking on several parameters. Results The etiological distribution: alcohol (67%), hepatitis C virus (HCV; 17%), HCV and alcohol (8%), hepatitis B virus (HBV; 3%), HBV and alcohol (3%), HBV and HCV (6%), and cryptogenic (3%). The laboratory results indicated an elevation of De Ritis level in 69% of cases and in 92% of total bilirubin values. The Halstead-Reitan (H-R) test score with regards to gender indicated that more than half of the patients had a score of 2, while only few cases received the scores 3 and 4. The frequency of H-R score with regards to Child-Pugh score showed the significant preponderance of Child-Pugh score of 7–9 (B): 58.3% compared to others groups of results, and these results indicated patients’ poor prognosis. Conclusion Findings showed the preponderance of female patients towards developing HE and the poor survival rate of patients older than 65 years. Alcohol and hepatitis C were the main causes associated with the development of HE. The neurological assessment marked the preponderance of Child-Pugh grades B and C and also the prevalence in female patients with neuropsychological disabilities through the assessment of H-R test.
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Harrison MF. The Misunderstood Coagulopathy of Liver Disease: A Review for the Acute Setting. West J Emerg Med 2018; 19:863-871. [PMID: 30202500 PMCID: PMC6123093 DOI: 10.5811/westjem.2018.7.37893] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 07/08/2018] [Accepted: 07/14/2018] [Indexed: 12/13/2022] Open
Abstract
The international normalized ratio (INR) represents a clinical tool to assess the effectiveness of vitamin-K antagonist therapy. However, it is often used in the acute setting to assess the degree of coagulopathy in patients with hepatic cirrhosis or acute liver failure. This often influences therapeutic decisions about invasive procedures or the need for potentially harmful and unnecessary transfusions of blood product. This may not represent a best-practice or evidence-based approach to patient care. The author performed a review of the literature related to the utility of INR in cirrhotic patients using several scientific search engines. Despite the commonly accepted dogma that an elevated INR in a cirrhotic patient corresponds with an increased hemorrhagic risk during the performance of invasive procedures, the literature does not support this belief. Furthermore, the need for blood-product transfusion prior to an invasive intervention is not supported by the literature, as this practice increases the risk of complications associated with a patient's hospital course. Many publications ranging from case studies to meta-analyses refute this evidence and provide examples of thrombotic events despite elevated INR values. Alternative methods, such as thromboelastogram, represent alternate means of assessing in vivo risk of hemorrhage in patients with acute or chronic liver disease in real-time in the acute setting.
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Affiliation(s)
- Michael F Harrison
- Henry Ford Hospital, Department of Emergency Medicine, Department of Internal Medicine, Department of Critical Care Medicine, Detroit, Michigan
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31
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Ronald J, Wang Q, Choi S, Suhocki P, Hall M, Smith T, Kim C. Albumin-bilirubin grade versus MELD score for predicting survival after transjugular intrahepatic portosystemic shunt (TIPS) creation. Diagn Interv Imaging 2018; 99:163-168. [PMID: 29154015 DOI: 10.1016/j.diii.2017.10.008] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Revised: 10/17/2017] [Accepted: 10/24/2017] [Indexed: 12/13/2022]
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Tohidinezhad F, Eslami S, Abu-Hanna A, Aliakbarian M. Model for End-Stage Liver Disease and Seven Derivations to Prioritize Liver Transplant Candidates: Which Is the Winner? EXP CLIN TRANSPLANT 2018; 16:721-729. [PMID: 29457445 DOI: 10.6002/ect.2017.0149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Under the present liver transplant policy, patients with the highest risk of death receive preference for organ placement. The aim of this study was to evaluate the Model for End-stage Liver Disease (MELD) and seven prognostic derivatives of this test for outcome prediction in cirrhotic patients on liver transplant wait lists. MATERIAL AND METHODS The study included 416 patients (65.9% male; age 49 ± 13.9 years) who were entered to liver transplant wait lists from January 2013 to October 2016. Study endpoints were 3-month, 6-month, and 1-year mortality. RESULTS All prognostic models had acceptable overall performances (0.12 < Brier score < 0.21). The MELD-to-serum sodium ratio test outperformed its counterparts at all 3 endpoints. Estimated C statistics ranged from 0.77 to 0.83. The largest value at 3 months was for the 5-variable MELD score (0.83), and the largest value at 6 months (0.82) and 1 year (0.83) was for the MELD-albumin score. The Hosmer-Lemeshow goodness-of-fit test and calibration plots revealed underestimation for the entire range of predicted risk (P < .001). With decision curve analysis, the MELD-to-serum sodium ratio and United Kingdom Model for End-Stage Liver Disease scoring tests covered the most extensive range of optimal threshold probabilities. CONCLUSIONS Although some derivations, including sodium and albumin, showed effective prioritization of liver transplant candidates, poor calibration statistics highlighted the need for a recalibration process as an inevitable prerequisite before daily clinical use of these tests at the individual level.
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Affiliation(s)
- Fariba Tohidinezhad
- The Student Research Committee, Department of Medical Informatics, Faculty of Medicine, Mashhad, Iran
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Somani V, Amarapurkar D, Shah A. Thromboelastography for Assessing the Risk of Bleeding in Patients With Cirrhosis-Moving Closer. J Clin Exp Hepatol 2017; 7:284-289. [PMID: 29234191 PMCID: PMC5715446 DOI: 10.1016/j.jceh.2017.03.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2016] [Accepted: 03/01/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Conventional coagulation tests (CCTs) in patients with cirrhosis only assess procoagulant factors and are poor predictors of bleeding risk. In spite of this knowledge, they are routinely used prior to invasive procedures, and attempts are made to correct these abnormalities before invasive procedures. These practices are not supported by the evidence and are harmful to the patients. METHODS This prospective study included 150 patients of cirrhosis undergoing invasive procedures. CCTs [bleeding time (BT), clotting time (CT), international normalized ratio (INR), activated partial thromboplastin time (aPTT) and platelet count], thromboplastin generation time (TGT) and thromboelastography (TEG) were done in all patients, and they were observed for post procedural bleeding. None of the patients received prophylactic transfusion before the procedure. RESULTS BT, CT and TGT were normal in all 150 patients. One of 150 patients developed clinically significant post procedural bleeding. No statistically significant association was seen among INR, aPTT, platelet count and Child class with bleeding. TEG values (R time and MA value) were normal in 61% and 75% patients respectively in spite of abnormal CCTs in most of them. Comparison of abnormal TEG values (R time and MA value) with INR and platelet count, respectively, in patients with no bleeding showed a statistically significant lower percentage of abnormal values of R time and MA value compared to INR and platelet count. CONCLUSION Abnormal CCTs in patients of cirrhosis do not predict bleeding risk. TEG may be useful in patients undergoing invasive procedures to assess bleeding risk and prevents erroneous prophylactic transfusions.
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Affiliation(s)
- Vaibhav Somani
- Department of Gastroenterology, Bombay Hospital and Medical Research Center, 12, New Marine Lines, Mumbai, Maharashtra 400020, India
| | - Deepak Amarapurkar
- Department of Gastroenterology, Bombay Hospital and Medical Research Center, 12, New Marine Lines, Mumbai, Maharashtra 400020, India
| | - Apurva Shah
- Department of Gastroenterology, Bombay Hospital and Medical Research Center, 12, New Marine Lines, Mumbai, Maharashtra 400020, India
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Kaiser T, Kinny-Köster B, Bartels M, Berg T, Scholz M, Engelmann C, Seehofer D, Becker S, Ceglarek U, Thiery J. Cholesterol esterification in plasma as a biomarker for liver function and prediction of mortality. BMC Gastroenterol 2017; 17:57. [PMID: 28427335 PMCID: PMC5397767 DOI: 10.1186/s12876-017-0614-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2016] [Accepted: 04/13/2017] [Indexed: 12/12/2022] Open
Abstract
Background Advanced stages of liver cirrhosis lead to a dramatically increased mortality. For valid identification of these patients suitable biomarkers are essential. The most important biomarkers for liver function are bilirubin and prothrombin time expressed as International Normalized Ratio (INR). However, the influence of several anticoagulants on the prothrombin time limits its diagnostic value. Aim of this study was the evaluation of cholesterol esterification (CE) fraction (esterified cholesterol vs. total cholesterol) as an alternative biomarker for liver synthesis and mortality prediction. Under physiological conditions the CE fraction in blood is closely regulated by lecithin-cholesterol acyltransferase (LCAT) which is produced in the liver. Methods One hundred forty-two patients with liver disease clinically considered for orthotopic liver transplant for different indications were enrolled in the study. One patient was excluded because of the intake of a direct oral factor Xa inhibitor which has a strong impact on prothrombin time. Results Results of CE fraction were in good agreement with INR (R2 = 0.73; p < 0.001). In patients who died or survived within three months mean CE fraction was 56% vs. 74% (p < 0.001) and mean INR was 2.0 vs. 1.3 (p < 0.001), respectively. The predictive value of CE fraction for three-month mortality risk was higher compared to INR (p = 0.04). Results for one-year mortality were comparable. Conclusions The cholesterol esterification fraction is a valid biomarker for liver synthesis and allows reliable prediction of mortality. In contrast to INR, it is independent of anticoagulation and other analytical limitations of coagulation tests. Electronic supplementary material The online version of this article (doi:10.1186/s12876-017-0614-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Thorsten Kaiser
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Paul-List-Str. 13-15, 04103, Leipzig, Germany.
| | - Benedict Kinny-Köster
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Paul-List-Str. 13-15, 04103, Leipzig, Germany
| | - Michael Bartels
- Department of Visceral, Vascular, Thoracic and Transplant Surgery, University Hospital Leipzig, Leipzig, Germany
| | - Thomas Berg
- Section of Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Markus Scholz
- Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University Hospital Leipzig, Leipzig, Germany
| | - Cornelius Engelmann
- Section of Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany
| | - Daniel Seehofer
- Department of Visceral, Vascular, Thoracic and Transplant Surgery, University Hospital Leipzig, Leipzig, Germany
| | - Susen Becker
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Paul-List-Str. 13-15, 04103, Leipzig, Germany.,LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany
| | - Uta Ceglarek
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Paul-List-Str. 13-15, 04103, Leipzig, Germany.,LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany
| | - Joachim Thiery
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Paul-List-Str. 13-15, 04103, Leipzig, Germany.,LIFE - Leipzig Research Center for Civilization Diseases, University Hospital Leipzig, Leipzig, Germany
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35
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Wang XX, Fang XX. Impact of coagulation function and anticoagulation therapy on liver fibrosis. Shijie Huaren Xiaohua Zazhi 2017; 25:897-903. [DOI: 10.11569/wcjd.v25.i10.897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Liver cirrhosis and its complications, including esophageal and gastric variceal bleeding, hepatic encephalopathy, and ascites, can cause serious harm to human health. Therefore, treatment of liver fibrosis is key to the prevention and treatment of liver cirrhosis. In order to treat liver fibrosis to reduce human suffering, medical experts and scholars have performed many clinical and animal studies to find safe, efficient and reliable drugs to slow the progression of hepatic fibrosis and even reverse the liver function. This review introduces the definition of liver fibrosis in China and other countries, discusses the effect of coagulation on the process of liver fibrosis and various anticoagulation therapies for liver fibrosis, and summarizes the advantages, disadvantages, and side effects of different anticoagulants in the prevention and treatment of liver fibrosis.
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36
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Dionigi E, Garcovich M, Borzio M, Leandro G, Majumdar A, Tsami A, Arvaniti V, Roccarina D, Pinzani M, Burroughs AK, O'Beirne J, Tsochatzis EA. Bacterial Infections Change Natural History of Cirrhosis Irrespective of Liver Disease Severity. Am J Gastroenterol 2017; 112:588-596. [PMID: 28220780 DOI: 10.1038/ajg.2017.19] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Accepted: 01/18/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES We assessed the prognostic significance of infections in relation to current prognostic scores and explored if infection could be considered per se a distinct clinical stage in the natural history of cirrhosis. METHODS We included consecutive patients with cirrhosis admitted to a tertiary referral liver unit for at least 48 h over a 2-year period. Diagnosis of infection was based on positive cultures or strict established criteria. We used competing risk analysis and propensity score matching for data analysis. RESULTS 501 patients (63% male, 48% alcoholic liver disease, median Model of End-stage Liver Disease (MELD)=17) underwent 781 admissions over the study period. Portal hypertensive bleeding and complicated ascites were the commonest reasons of admission. The incidence of proven bacterial infection was 25.6% (60% community acquired and 40% nosocomial). Survival rates at 3, 6, 12, and 30 months were 83%, 77%, 71%, and 62% in patients without diagnosis of infection, vs. 50%, 46%, 41%, and 34% in patients with diagnosis of infection. Overall survival was independently associated with MELD score (hazards ratio (HR) 1.099), intensive care (ITU) stay (HR 1.967) and bacterial infection (HR 2.226). Bacterial infection was an independent predictor of survival even when patients who died within the first 30 days were excluded from the analysis in Cox regression (HR 2.013) and competing risk Cox models in all patients (HR 1.46) and propensity risk score-matched infected and non-infected patients (HR 1.67). CONCLUSIONS Infection most likely represents a distinct prognostic stage of cirrhosis, which affects survival irrespective of disease severity, even after recovery from the infective episode.
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Affiliation(s)
- Elena Dionigi
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK
- Unità di Gastroenterologia, Azienda Ospedaliera di Melegnano, Vizzolo Predabissi, Italy
| | - Matteo Garcovich
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK
| | - Mauro Borzio
- Unità di Gastroenterologia, Azienda Ospedaliera di Melegnano, Vizzolo Predabissi, Italy
| | - Gioacchino Leandro
- National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Avik Majumdar
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK
| | - Aikaterini Tsami
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK
| | - Vasiliki Arvaniti
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK
| | - Davide Roccarina
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK
| | - Massimo Pinzani
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK
| | - Andrew K Burroughs
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK
| | - James O'Beirne
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK
| | - Emmanuel A Tsochatzis
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK
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Abstract
The state of clinical art of the coagulopathy of cirrhosis changed considerably over the last decade. Until 2005, cirrhosis was considered as the epitome of the hemorrhagic coagulopathies and the abnormal hemostasis tests associated with the disease were corrected with infusion of fresh frozen plasma or platelets to minimize the risk of bleeding. Since that time, a great deal of work has been done and there is now a change of paradigm. The prothrombin time once considered as an isolated measure of bleeding risk was rejected, and cirrhosis shifted from a purely hemorrhagic construct to a mixed and thrombosis-prone paradigm. In this article we examine the interesting history of how these conceptual changes came about.
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Shiha G, Ibrahim A, Helmy A, Sarin SK, Omata M, Kumar A, Bernstien D, Maruyama H, Saraswat V, Chawla Y, Hamid S, Abbas Z, Bedossa P, Sakhuja P, Elmahatab M, Lim SG, Lesmana L, Sollano J, Jia JD, Abbas B, Omar A, Sharma B, Payawal D, Abdallah A, Serwah A, Hamed A, Elsayed A, AbdelMaqsod A, Hassanein T, Ihab A, GHaziuan H, Zein N, Kumar M. Asian-Pacific Association for the Study of the Liver (APASL) consensus guidelines on invasive and non-invasive assessment of hepatic fibrosis: a 2016 update. Hepatol Int 2017; 11:1-30. [PMID: 27714681 DOI: 10.1007/s12072-016-9760-3] [Citation(s) in RCA: 163] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 08/13/2016] [Indexed: 12/14/2022]
Abstract
Hepatic fibrosis is a common pathway leading to liver cirrhosis, which is the end result of any injury to the liver. Accurate assessment of the degree of fibrosis is important clinically, especially when treatments aimed at reversing fibrosis are being evolved. Despite the fact that liver biopsy (LB) has been considered the "gold standard" of assessment of hepatic fibrosis, LB is not favored by patients or physicians owing to its invasiveness, limitations, sampling errors, etc. Therefore, many alternative approaches to assess liver fibrosis are gaining more popularity and have assumed great importance, and many data on such approaches are being generated. The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on liver fibrosis in 2007, with a mandate to develop consensus guidelines on various aspects of liver fibrosis relevant to disease patterns and clinical practice in the Asia-Pacific region. The first consensus guidelines of the APASL recommendations on hepatic fibrosis were published in 2009. Due to advances in the field, we present herein the APASL 2016 updated version on invasive and non-invasive assessment of hepatic fibrosis. The process for the development of these consensus guidelines involved review of all available published literature by a core group of experts who subsequently proposed consensus statements followed by discussion of the contentious issues and unanimous approval of the consensus statements. The Oxford System of the evidence-based approach was adopted for developing the consensus statements using the level of evidence from one (highest) to five (lowest) and grade of recommendation from A (strongest) to D (weakest). The topics covered in the guidelines include invasive methods (LB and hepatic venous pressure gradient measurements), blood tests, conventional radiological methods, elastography techniques and cost-effectiveness of hepatic fibrosis assessment methods, in addition to fibrosis assessment in special and rare situations.
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Affiliation(s)
- Gamal Shiha
- Internal Medicine Department, El-Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt.
- Egyptian Liver Research Institute And Hospital (ELRIAH), Mansoura, Egypt.
| | - Alaa Ibrahim
- Department of Internal medicine, University of Benha, Benha, Egypt
| | - Ahmed Helmy
- Department of Tropical Medicine & Gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
| | - Masao Omata
- Department of Gastroenterology, University of Tokyo, Tokyo, Japan
| | - Ashish Kumar
- Department of Gastroenterology & Hepatology, Ganga Ram Institute for Postgraduate Medical Education & Research of Sir Ganga Ram Hospital, New Delhi, India
| | - David Bernstien
- Division of Hepatology, North Shore University Hospital and Long Island Jewish Medical Center, New Hyde Park, New York, USA
| | - Hitushi Maruyama
- Department of Gastroenterology, Chiba University Graduate School of Medicine, Chiba, Chiba Prefecture, Japan
| | - Vivek Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Yogesh Chawla
- Post Graduate Institute of Medial Education & Research, Chandigarh, India
| | - Saeed Hamid
- Department of Medicine, The Aga Khan University & Hospital, Stadium Road, Karachi, Pakistan
| | - Zaigham Abbas
- Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Pierre Bedossa
- Department of Pathology, Physiology and Imaging, University Paris Diderot, Paris, France
| | - Puja Sakhuja
- Govind Ballabh Pant Hospital, Maulana Azad Medical College, New Delhi, India
| | - Mamun Elmahatab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Seng Gee Lim
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | | | - Jose Sollano
- University of Santo Tomas, España Blvd, Manila, Philippines
| | - Ji-Dong Jia
- Liver Research Centre at the Beijing Friendship Hospital, Capital University in Beijing, Beijing, China
| | - Bahaa Abbas
- Department of Internal Medicine, Military Medical Academy, Cairo, Egypt
| | - Ashraf Omar
- Tropical Medicine Department, Cairo Medical School, Cairo, Egypt
| | - Barjesh Sharma
- Department of Gastroenterology, GB Pant Hospital, New Delhi, India
| | - Diana Payawal
- Section of Gastroenterology, Cardinal Santos Medical Center, San Juan City, Metro Manila, Philippines
| | - Ahmed Abdallah
- Pediatric Hospital, Mansoura University, Mansoura, Egypt
| | | | - Abdelkhalek Hamed
- Hepatology and Diabetes Unit, Military Medical Academy, Cairo, Egypt
| | - Aly Elsayed
- Hepatology & GIT Department, AHF Center Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Amany AbdelMaqsod
- Internal Medicine Department, Faculty of Medicine Cairo University, Liver Transplant Unit Manial Hospital and Liver ICU French Hospital, Cairo University, Cairo, Egypt
| | | | - Ahmed Ihab
- Molecular Pathology Unit & Research Group, German University in Cairo, Cairo, Egypt
| | - Hamsik GHaziuan
- Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia
| | - Nizar Zein
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, USA
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
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Kumral D, Caldwell SH, Argo CK. Impact of an Institutional Change in Prothrombin Time Methodology on INR and MELD Scores in Liver Transplant Evaluations. J Clin Lab Anal 2016; 30:968-971. [PMID: 27076282 DOI: 10.1002/jcla.21964] [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: 07/30/2015] [Revised: 11/04/2015] [Accepted: 02/09/2016] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Allocation of liver grafts based on the model for end-stage liver disease (MELD) has been questioned because the prothrombin time (PT) measurement in cirrhosis patients changes with different commercially available thromboplastin reagents due to variations in the international sensitivity index (ISI). Our hospital laboratory electively changed the thromboplastin used in the PT/INR from PT-HS (ISI of 1.464) to Recombiplastin (ISI of 0.870). Theoretically, this change may yield lower INR and MELD scores in cirrhosis patients at our institution and thus impact access to organs. METHODS 27 patients listed for liver transplant prior to change in thromboplastin (Cohort A) were compared to 36 patients listed after the change (Cohort B). RESULTS Patients in Cohort A had a mean INR of 1.41 and mean MELD of 13.9 compared to Cohort B with a mean INR of 1.39 and mean MELD of 13.8. Student's t-tests showed no statistically significant difference in INR (p = 0.799) or MELD (p = 0.955) between cohorts. CONCLUSION We expected overall INR and MELD scores to decrease following the change to a thromboplastin with a lower ISI. On the contrary, we found no evidence of a major trend in these values supporting the relative robustness of the MELD.
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Affiliation(s)
- Dennis Kumral
- Department of Medicine, University of Virginia Health System, Charlottesville, Virginia
| | - Stephen H Caldwell
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, Virginia
| | - Curtis K Argo
- Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, Virginia.
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Tripodi A, Primignani M, Braham S, Chantarangkul V, Clerici M, Moia M, Peyvandi F. Coagulation parameters in patients with cirrhosis and portal vein thrombosis treated sequentially with low molecular weight heparin and vitamin K antagonists. Dig Liver Dis 2016; 48:1208-13. [PMID: 27470055 DOI: 10.1016/j.dld.2016.06.027] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 05/19/2016] [Accepted: 06/24/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS Information on coagulation for cirrhotics on anticoagulants is scanty. We investigated plasma from 23 cirrhotics treated with low-molecular-weight-heparin (LMWH) followed by vitamin K antagonists (VKA). METHODS On days 1-4 patients received full-dose LMWH. On day-5 VKA was started and LMWH was terminated when INR therapeutic-interval was reached. Blood was collected at peak and trough during LMWH, LMWH+VKA and VKA. Non-cirrhotics on VKA were included as controls. RESULTS Anti-factor Xa increased from baseline-to-peak during LMWH. During LMWH+VKA was high and reverted to zero during VKA. INR was slightly high at baseline, trough or peak during LMWH and increased to 2.2 during LMWH+VKA or VKA. Mean VKA weekly-doses for cirrhotics and controls were 28.5mg and 28.6mg. Protein C decreased upon VKA, but not to the expected extent. Endogenous-thrombin-potential (ETP) decreased from baseline (1436nMmin) to trough (1258nMmin) and peak (700nMmin) during LMWH and was further reduced during LMWH+VKA (395nMmin). CONCLUSIONS Target-INR for cirrhotics can be reached by VKA dosages similar to those for non-cirrhotics. ETP reduction parallels the effect of LMWH and/or VKA. Whether these parameters represent the antithrombotic action elicited by these drugs remains to be determined by clinical-trials and laboratory-measurements. ETP, being a global-test reflecting both pro- and anti-coagulants targeted by antithrombotic drugs, seems the candidate for these trials.
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Affiliation(s)
- Armando Tripodi
- Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy; IRCCS Maggiore Hospital Foundation, Milano, Italy.
| | - Massimo Primignani
- First Division of Gastroenterology, Italy; IRCCS Maggiore Hospital Foundation, Milano, Italy
| | - Simon Braham
- Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy; IRCCS Maggiore Hospital Foundation, Milano, Italy
| | - Veena Chantarangkul
- Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy; IRCCS Maggiore Hospital Foundation, Milano, Italy
| | - Marigrazia Clerici
- Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy; IRCCS Maggiore Hospital Foundation, Milano, Italy
| | - Marco Moia
- Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy; IRCCS Maggiore Hospital Foundation, Milano, Italy
| | - Flora Peyvandi
- Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy; IRCCS Maggiore Hospital Foundation, Milano, Italy
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Proposal for new diagnostic criteria for DIC from the Japanese Society on Thrombosis and Hemostasis. Thromb J 2016; 14:42. [PMID: 27708553 PMCID: PMC5039801 DOI: 10.1186/s12959-016-0117-x] [Citation(s) in RCA: 133] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 09/05/2016] [Indexed: 01/15/2023] Open
Abstract
Disseminated intravascular coagulation (DIC) is a serious disease that, in the presence of underlying disease, causes persistent, generalized, marked coagulation activation. Early treatment based on an appropriate diagnosis is very important for improving patients’ prognosis, to which end diagnostic criteria play a key role. Several criteria have been proposed, but each has its strengths and weaknesses, and improved criteria are needed. Widespread use of coagulofibrinolytic markers has elucidated that the pathology of DIC differs greatly as a function of the underlying disease. Thus, discriminating use of DIC diagnostic criteria that take underlying diseases into account is important. DIC diagnostic criteria that are well known in Japan include the Japanese Ministry of Health and Welfare’s old DIC diagnostic criteria (JMHW criteria), the International Society on Thrombosis and Haemostasis’s DIC diagnostic criteria (ISTH criteria), and the Japanese Association for Acute Medicine’s acute-stage DIC diagnostic criteria (JAAM criteria). Those criteria have their respective drawbacks: the sensitivity of the ISTH criteria is poor, the JAAM criteria cannot be applied to all underlying diseases, and the JMHW criteria have poor sensitivity in the case of infections, do not use molecular markers, and result in misdiagnosis. The Japanese Society on Thrombosis and Hemostasis’s newly proposed provisional draft DIC diagnostic criteria (new criteria) use diagnostic criteria classifications of “hematopoietic disorder type”, “infectious type”, and “basic type” based on the underlying pathology. For the hematopoietic disorder type the platelet count is omitted from the score, while for the infectious type, fibrinogen is omitted from the score. Also, points are added if the platelet count decreases with time. In the new criteria, molecular markers and antithrombin activity have been newly included, and as a countermeasure for misdiagnosis, 3 points are deducted if there is liver failure. In this paper, we discuss various problems encountered with DIC diagnosis, and we describe the new criteria together with the events that led to their creation. These new diagnostic criteria take into account the underlying diseases of wide area, and we expect that they will serve clinicians well due to the above adaptations and improvements.
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42
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Huang WT, Cang WC, Derry KL, Lane JR, von Drygalski A. Four-Factor Prothrombin Complex Concentrate for Coagulopathy Reversal in Patients With Liver Disease. Clin Appl Thromb Hemost 2016; 23:1028-1035. [DOI: 10.1177/1076029616668406] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
A 4-factor prothrombin complex concentrate (4F-PCC, Kcentra®) was recently approved in the United States for the reversal of vitamin K antagonist-associated major bleeding, but it is often used to reverse coagulopathy in patients with liver disease (LD). This single-center, retrospective study analyzed the efficacy and safety of 4F-PCC administered in patients with and without LD. Prothrombin time/International Normalized Ratio (PT/INR) reversal with 4F-PCC was attempted in 85 patients; LD was documented in 31 patients. Coagulopathy reversal and hemostasis with 4F-PCC were inferior in patients with LD compared to patients without LD. Coagulopathy reversal, defined as INR = 1.5 after 4F-PCC administration, was achieved in 6 (19.4%) LD patients, compared to 44 (81.5%) non-LD patients ( p < 0.01). Hemostasis was achieved in 6 LD patients (19.4%) compared to 23 non-LD patients (42.6%) ( p = 0.03). Thromboembolic events occurred in 1 LD patient (3.2%) and 8 non-LD patients (14.8%) ( p = 0.15). Mortality was 51.6% in LD patients and 18.5% in non-LD patients ( p < 0.01). These observations suggest that the efficacy of 4F-PCC is suboptimal to correct coagulopathy and hemostasis in patients with LD, who have high rates of in-hospital mortality due to sequelae of LD. The incidence of thromboembolic events appeared comparable, suggesting that 4F-PCC does not cause undue thromboembolism in LD patients. In conclusion, 4F-PCC appears to be safe in LD patients when administered judiciously; however, further studies are necessary to optimize its use and elucidate its hemostatic potential in this patient population.
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Affiliation(s)
- Wan-Ting Huang
- UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, USA
| | - William C. Cang
- UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, USA
| | - Katrina L. Derry
- UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, USA
| | - James R. Lane
- UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, USA
| | - Annette von Drygalski
- Department of Medicine, Hemophilia and Thrombosis Treatment Center, University of California San Diego, San Diego, CA, USA
- The Scripps Research Institute, La Jolla, CA, USA
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Andriulli A, Tripodi A, Angeli P, Senzolo M, Primignani M, Giannini EG, Riggio O, Colli A, Prati D, Sacerdoti D, Merkel C, Basili S, Ferro D, Villa E, Di Minno G, Caraceni P, Marzioni M, Mannucci PM, Violi F, Piscaglia F, Calvaruso V, De Pietri L, Falcone M, Feltracco P, Grandone E, La Mura V, Licata A, Lucidi C, Maimone S, Marietta M, Morisco F, Napoleone L, Piano S, Raparelli V, Rebulla P, Ribero D, Sartori MT, Scalera A, Schepis F, Siciliano M, Baroni GS, Tufano A, Vitale A, Zuin M. Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference. Dig Liver Dis 2016; 48:455-467. [PMID: 27012444 DOI: 10.1016/j.dld.2016.02.008] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 02/18/2016] [Indexed: 12/11/2022]
Abstract
Patients with cirrhosis present with hemostatic alterations secondary to reduced availability of pro-coagulant and anti-coagulant factors. The net effect of these changes is a rebalanced hemostatic system. The Italian Association of the Study of the Liver (AISF) and the Italian Society of Internal Medicine (SIMI) promoted a consensus conference on the hemostatic balance in patients with cirrhosis. The consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Rome in December 2014. The statements were graded according to quality of evidence and strength of recommendations, and approved by an independent jury. The statements presented here highlight strengths and weaknesses of current laboratory tests to assess bleeding and thrombotic risk in cirrhotic patients, the pathophysiology of hemostatic perturbations in this condition, and outline the optimal management of bleeding and thrombosis in patients with liver cirrhosis.
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Bishop MA, Streiff MB. Effects of anticoagulation provider continuity on time in therapeutic range for warfarin patients. J Thromb Thrombolysis 2016; 42:283-7. [PMID: 27085542 DOI: 10.1007/s11239-016-1359-y] [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: 12/30/2022]
Abstract
Anticoagulation (AC) clinics use the percentage of time in the therapeutic INR range (%TTR) to characterize the quality of management for patients treated with warfarin. In order to guide policy and procedure changes, the purpose of this quality improvement (QI) study was to characterize the AC patient population at The Johns Hopkins Hospital (JHH). We set out to investigate the impact of AC clinic provider continuity on the quality of anticoagulation management. This QI study is a retrospective chart review of 525 warfarin patients managed by pharmacists in the Hematology AC Management Clinic at JHH from June 28, 2013 to November 1, 2014. We recorded patient demographic and clinical characteristics and the quality of AC management using %TTR, and compared these parameters between patients with (Group A) and without a primary AC (Group B). Group A patients had a significantly higher %TTR than Group B patients (53.2 vs. 46.5 %, p = 0.008). In conclusion, we found that patients with a primary AC clinic provider had a higher %TTR than patients with multiple providers. If confirmed prospectively, this approach to warfarin management could represent one technique for AC clinics to optimize patient management and clinical outcomes.
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Affiliation(s)
- Martin A Bishop
- Division of Ambulatory and Care Transitions, Department of Pharmacy, The Johns Hopkins Hospital, 600 N. Wolfe Street, Carnegie 180, Baltimore, MD, 21287, USA.
| | - Michael B Streiff
- Departments of Medicine and Pathology, Johns Hopkins University School of Medicine, 1830 Monument Street, Suite 7300, Baltimore, MD, 21205, USA
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Xu R, Chang J, Huang H, Deng ZH, Ji YY. Relationship between clinical parameters and degree of liver fibrosis and risk factors for significant liver fibrosis in patients with chronic hepatitis B: A Logistic regression analysis. Shijie Huaren Xiaohua Zazhi 2016; 24:279-286. [DOI: 10.11569/wcjd.v24.i2.279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the relationship between the severity of fibrosis and clinical parameters in patients with chronic hepatitis B (CHB), and to analyze risk factors for significant liver fibrosis in CHB patients.
METHODS: A total of 76 biopsy-proven CHB cases treated from January 2012 to July 2015 at the Second Hospital Affiliated to Kunming Medical University were included in the study. Gender, age, blood count variables including white blood cells, hemoglobin (HB), platelet count (PLT), red blood cell distribution width (RDW), mean platelet volume (MPV), as well as albumin (ALB), globin (GLO), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), total bilirubin (TB), prothrombin time (PT) and serum HBV DNA were recorded. Relationship between these parameters and liver fibrosis stage and risk factors for significant liver fibrosis were analyzed.
RESULTS: With the increase in the severity of liver fibrosis, white blood cells, HB, PLT, and ALB gradually decreased, and RDW, GLB, AST, PT, GGT increased; all of these parameters had significant differences between the S1-S4 groups (P < 0.05). Spearman correlation analysis showed that there was a positive correlation between ALT, AST, GGT, TB, GLO, PT, RDW, MPV, age and liver stage of fibrosis, and a negative correlation between liver stage of fibrosis and ALB, white blood cells, HB, and PLT. In logistic regression analysis, PLT was identified as an independent risk factor for significant liver fibrosis in CHB.
CONCLUSION: ALT is not predictive of liver fibrosis stage. PLT is an independent risk factor for significant liver fibrosis in CHB. Liver histopathology can be recommended for CHB patients with older age, lower PLT, even though ALT is normal or only mildly elevated.
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46
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Tripodi A, Lippi G, Plebani M. How to report results of prothrombin and activated partial thromboplastin times. ACTA ACUST UNITED AC 2016; 54:215-22. [DOI: 10.1515/cclm-2015-0657] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Accepted: 07/15/2015] [Indexed: 11/15/2022]
Abstract
AbstractProthrombin time (PT) and activated partial thromboplastin time (APTT) are the most widely used tests to investigate coagulation abnormalities. Varied result reporting have been introduced over the years for the two tests, thus making their interpretation rather confusing in different clinical settings. PT results have been reported as clotting time, percentage activity, PT-ratio (patient-to-normal clotting time) and as international normalized ratio (INR). The INR scale has been devised to harmonize results stemming from different thromboplastins from patients on treatment with vitamin K antagonists. Therefore, there are some theoretical and evidence-based considerations that make the INR formally invalid when the test is used to analyze patients in other clinical settings. Unfortunately, this limitation has been frequently overlooked, and the INR has been (and is currently) used as a universal system of results harmonization. The APTT has been historically reported as clotting time or as ratio (patient-to-normal clotting time). In this opinion paper we review the current state-of-the-art for result reporting and attempt to give practical guidance on how PT and APTT should be reported in different clinical conditions for which the tests are requested.
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47
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Asrani SK, Kamath PS. Model for end-stage liver disease score and MELD exceptions: 15 years later. Hepatol Int 2015; 9:346-54. [PMID: 26016462 DOI: 10.1007/s12072-015-9631-3] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Accepted: 04/06/2015] [Indexed: 02/06/2023]
Abstract
The model for end-stage liver disease (MELD) score has been used as an objective scale of disease severity for management of patients with end-stage liver disease; it currently serves as the basis of an urgency-based organ-allocation policy in several countries. Implementation of the MELD score led to a reduction in waiting-list registration and waiting-list mortality and an increase in the number of deceased-donor transplants without adversely affecting long-term outcomes after liver transplantation (LT). The MELD score has been used for management of non-transplant patients with chronic liver disease. MELD exceptions serve as a mechanism to advance the needs of subsets of patients with liver disease not adequately addressed by MELD-based organ allocation. Several models have been proposed to refine and improve the MELD score as the environment within which it operates continues to evolve toward transplantation for sicker patients. The MELD score continues to serve and be used as a template to improve upon as an objective gauge of disease severity and as a metric enabling optimization of allocation of scarce donor organs for LT.
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Affiliation(s)
- Sumeet K Asrani
- Baylor University Medical Center, 3410 Worth Street Suite 860, Dallas, TX, 75246, USA,
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48
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Kaiser T, Zeuzem S, Lichtinghagen R, Welker MW, Geilenkeuser WJ, Kruse R, Neumaier M, Thiery J, Schmidt M. Multi-center proficiency tests for Lab-MELD score diagnostics to improve the quality and safety for patients awaiting liver transplantation. Clin Chem Lab Med 2015; 52:e287-9. [PMID: 24960153 DOI: 10.1515/cclm-2014-0088] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Accepted: 06/03/2014] [Indexed: 11/15/2022]
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Shatzel J, Dulai PS, Harbin D, Cheung H, Reid TN, Kim J, James SL, Khine H, Batman S, Whyman J, Dickson RC, Ornstein DL. Safety and efficacy of pharmacological thromboprophylaxis for hospitalized patients with cirrhosis: a single-center retrospective cohort study. J Thromb Haemost 2015; 13:1245-53. [PMID: 25955079 PMCID: PMC6658183 DOI: 10.1111/jth.13000] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2014] [Accepted: 04/23/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND Hospitalized patients with cirrhosis are at increased risk for venous thromboembolism (VTE). The benefits and risks of pharmacological thromboprohylaxis in these patients have not been well studied. OBJECTIVES To examine the safety and efficacy of pharmacological VTE prophylaxis in hospitalized cirrhotic patients. PATIENTS/METHODS Retrospective cohort study of patients with cirrhosis hospitalized at an academic tertiary care referral center over a 5-year period. RESULTS Six hundred hospital admissions accounting for 402 patients were included. VTE prophylaxis was administered during 296 (49%) admissions. Patients receiving VTE prophylaxis were older (59 years vs. 55 years, P < 0.001), had longer lengths of stay (9.6 days vs. 6.8 days, P = 0.002), and lower Model for End-Stage Liver Disease scores (13.2 vs. 16.1, P < 0.001). In-hospital bleeding events (8.1% vs. 5.5%, P = 0.258), gastrointestinal bleeding events (3.0% vs. 3.2% P = 0.52), new VTE events (2.37% vs. 1.65%, P = 0.537), and mortality (8.4% vs. 7.3%, P = 0.599) were similar in the two groups. VTE prophylaxis did not reduce the risk of VTE (odds ratio 0.94, 95% confidence interval 0.23-3.71), and patients receiving unfractionated heparin, but not low molecular weight heparin, were at increased risk for in-hospital bleeding events (odds ratio 2.38, 95% confidence interval 1.15-4.94 vs. 0.87, 0.37-2.05, respectively). CONCLUSION The rate of VTE in this cohort of hospitalized cirrhotic patients was low and was unaffected by pharmacological thromboprophylaxis. Unfractionated heparin was associated with an increased risk for in-hospital bleeding, suggesting that if thromboprophylaxis is indicated, low molecular weight heparin may be favored.
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Affiliation(s)
- J Shatzel
- Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - P S Dulai
- Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - D Harbin
- Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - H Cheung
- Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - T N Reid
- Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - J Kim
- Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - S L James
- Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - H Khine
- Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - S Batman
- Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - J Whyman
- Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - R C Dickson
- Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
- Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - D L Ornstein
- Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
- Geisel School of Medicine at Dartmouth, Hanover, NH, USA
- Department of Pathology, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
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50
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Clinical usefulness of international normalized ratio calibration of prothrombin time in patients with chronic liver disease. Int J Hematol 2015; 102:163-9. [DOI: 10.1007/s12185-015-1820-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Revised: 05/20/2015] [Accepted: 06/03/2015] [Indexed: 12/14/2022]
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