AGA Clinical Practice Update: Coagulation in Cirrhosis

DescriptionThis expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The intent is to evaluate the current data on mechanism of altered coagulation in patients with cirrhosis, provide guidance on the use of currently available testing of the coagulation cascade, and help practitioners use anticoagulation and pro-coagulants appropriately in patients with cirrhosis.MethodsThis review is framed around the best practice points, which were derived from the most impactful publications in the area of coagulation in cirrhosis and agreed to by all authors.Best practice advice 1Global tests of clot formation, such as rotational thromboelastometry, thromboelastography, sonorheometry, and thrombin generation, may eventually have a role in the evaluation of clotting in patients with cirrhosis, but currently lack validated target levels.Best practice advice 2In general, clinicians should not routinely correct thrombocytopenia and coagulopathy before low-risk therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation in patients with hepatic synthetic dysfunction–induced coagulation abnormalities.Best practice advice 3Blood products should be used sparingly because they increase portal pressure and carry a risk of transfusion-associated circulatory overload, transfusion-related acute lung injury, infection transmission, alloimmunization, and/or transfusion reactions.Best practice advice 4The following transfusion thresholds for management of active bleeding or high-risk procedures may optimize clot formation in advanced liver disease: hematocrit ≥25%, platelet count >50,000, and fibrinogen >120 mg/dL. Commonly utilized thresholds for international normalized ratio correction are not supported by evidence.Best practice advice 5Thrombopoietin agonists are a good alternative to platelet transfusion, but require time (about 10 days) to elevate platelet levels.Best practice advice 6The large volume of fresh frozen plasma required to reach an arbitrary international normalized ratio target, limitations of the usual target, minimal effect on thrombin generation, and adverse effects on portal pressure limit the utility of this agent significantly.Best practice advice 7The 4-factor prothrombin complex concentrate contains both pro- and anticoagulant factors that offer an attractive low-volume therapeutic to rebalance a disturbed hemostatic system. However, dosage is, in part, based on international normalized ratio, which is problematic in cirrhosis, and published experience in liver disease is limited.Best practice advice 8Anti-fibrinolytic therapy may be considered in patients with persistent bleeding from mucosal oozing or puncture wound bleeding consistent with impaired clot integrity. Both ε-aminocaproic acid and tranexamic acid inhibit clot dissolution. Neither is believed to generate a hypercoagulable state, although both may exacerbate pre-existing thrombi.Best practice advice 9Desmopressin releases von Willebrand factor as its primary hemostatic mechanism. As this factor is usually elevated in cirrhosis, the agent lacks a sound evidence-based foundation, but may be useful in patients with concomitant renal failure.Best practice advice 10Systemic heparin infusion is recommended for symptomatic deep vein thrombosis and portal and mesenteric vein thrombosis, but there are unresolved issues regarding monitoring with both the anti-Xa assay and the partial thromboplastin time due to cirrhosis-related antithrombin deficiency (heparin cofactor).Best practice advice 11Treatment of incidental portal and mesenteric vein thrombosis depends on estimated impact on transplantation surgical complexity vs risks of bleeding and falls. Therapy with low-molecular-weight heparin, vitamin K antagonists, and direct-acting anticoagulants improve portal vein repermeation vs observation alone.Best practice advice 12Direct-acting anticoagulants, such as the factor Xa and thrombin inhibitors, are relatively safe and effective in stable cirrhotic patients, but are in need of further study in patients with more advanced liver disease. This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The intent is to evaluate the current data on mechanism of altered coagulation in patients with cirrhosis, provide guidance on the use of currently available testing of the coagulation cascade, and help practitioners use anticoagulation and pro-coagulants appropriately in patients with cirrhosis. This review is framed around the best practice points, which were derived from the most impactful publications in the area of coagulation in cirrhosis and agreed to by all authors. Global tests of clot formation, such as rotational thromboelastometry, thromboelastography, sonorheometry, and thrombin generation, may eventually have a role in the evaluation of clotting in patients with cirrhosis, but currently lack validated target levels. In general, clinicians should not routinely correct thrombocytopenia and coagulopathy before low-risk therapeutic paracentesis, thoracentesis, and routine upper endoscopy for variceal ligation in patients with hepatic synthetic dysfunction–induced coagulation abnormalities. Blood products should be used sparingly because they increase portal pressure and carry a risk of transfusion-associated circulatory overload, transfusion-related acute lung injury, infection transmission, alloimmunization, and/or transfusion reactions. The following transfusion thresholds for management of active bleeding or high-risk procedures may optimize clot formation in advanced liver disease: hematocrit ≥25%, platelet count >50,000, and fibrinogen >120 mg/dL. Commonly utilized thresholds for international normalized ratio correction are not supported by evidence. Thrombopoietin agonists are a good alternative to platelet transfusion, but require time (about 10 days) to elevate platelet levels. The large volume of fresh frozen plasma required to reach an arbitrary international normalized ratio target, limitations of the usual target, minimal effect on thrombin generation, and adverse effects on portal pressure limit the utility of this agent significantly. The 4-factor prothrombin complex concentrate contains both pro- and anticoagulant factors that offer an attractive low-volume therapeutic to rebalance a disturbed hemostatic system. However, dosage is, in part, based on international normalized ratio, which is problematic in cirrhosis, and published experience in liver disease is limited. Anti-fibrinolytic therapy may be considered in patients with persistent bleeding from mucosal oozing or puncture wound bleeding consistent with impaired clot integrity. Both ε-aminocaproic acid and tranexamic acid inhibit clot dissolution. Neither is believed to generate a hypercoagulable state, although both may exacerbate pre-existing thrombi. Desmopressin releases von Willebrand factor as its primary hemostatic mechanism. As this factor is usually elevated in cirrhosis, the agent lacks a sound evidence-based foundation, but may be useful in patients with concomitant renal failure. Systemic heparin infusion is recommended for symptomatic deep vein thrombosis and portal and mesenteric vein thrombosis, but there are unresolved issues regarding monitoring with both the anti-Xa assay and the partial thromboplastin time due to cirrhosis-related antithrombin deficiency (heparin cofactor). Treatment of incidental portal and mesenteric vein thrombosis depends on estimated impact on transplantation surgical complexity vs risks of bleeding and falls. Therapy with low-molecular-weight heparin, vitamin K antagonists, and direct-acting anticoagulants improve portal vein repermeation vs observation alone. Direct-acting anticoagulants, such as the factor Xa and thrombin inhibitors, are relatively safe and effective in stable cirrhotic patients, but are in need of further study in patients with more advanced liver disease. Coagulation disorders are an integral component of liver disease and constitute a key aspect of most prognostic scores. Bleeding issues have been the dominant clinical problem for many years, but inappropriate clotting is now recognized and is attributed to changes in the hemostatic balance.1Intagliata N.M. Argo C.K. Stine J.G. et al.Concepts in coagulation in liver disease: a summary of the 7th International Coagulation In Liver Disease Conference.Thromb Haemost. 2018; 118: 1491-1506Crossref PubMed Scopus (111) Google Scholar, 2Joist J.H. AICF and DIC in liver cirrhosis: expressions of a hypercoagulable state.Am J Gastroenterol. 1999; 94: 2801-2803Crossref PubMed Google Scholar Bleeding can be broadly divided into (1) portal pressure driven with less relevance of hemostatic mechanisms and (2) mucosal or puncture wound bleeding, which often has a component of premature clot dissolution or hyperfibrinolysis, which in liver disease has been named accelerated intravascular coagulation and fibrinolysis (AICF).2Joist J.H. AICF and DIC in liver cirrhosis: expressions of a hypercoagulable state.Am J Gastroenterol. 1999; 94: 2801-2803Crossref PubMed Google Scholar The mechanism of hyperfibrinolysis remains uncertain but involves changes in the thrombolytic system.3Rijken D.C. Kock E.L. Guimaraes A.H. et al.Evidence for an enhanced fibrinolytic capacity in cirrhosis as measured with two different global fibrinolysis tests.J Thromb Haemost. 2012; 10: 2116-2122Crossref PubMed Scopus (67) Google Scholar Liver-derived dysfibrinogen may act as a counterforce to clot dissolution.4Hugenholtz G.C. Macrae F. Adelmeijer J. et al.Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen.J Thromb Haemost. 2016; 14: 1054-1066Crossref PubMed Scopus (86) Google Scholar Inappropriate clotting is seen especially in portal vein thrombosis (PVT) and mesenteric vein thrombosis, but also in peripheral limb deep vein thrombosis (DVT). These often warrant challenging considerations of anticoagulant therapy or prophylaxis. Hypercoagulability can also contribute to liver atrophy through microthrombosis.5Wanless I.R. Wong F. Blendis L.M. et al.Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portal hypertension.Hepatology. 1995; 21: 1238-1247PubMed Google Scholar A number of key changes in hemostatic pathways have been elucidated—some favor bleeding and others favor clotting (Figure 1). In stable cirrhosis, the system is rebalanced by off-setting factors, but generally the balance is regarded as precarious and significantly influenced by other factors, such as volume status, systemic infection, and renal function. Thrombocytopenia is probably the best-known change and is attributed to splenic sequestration and decreased thrombopoietin (TPO). Platelet dysfunction has also been described, but these anticoagulant changes are significantly offset by increased endothelial-derived von Willebrand factor (vWF).6Lisman T. Bongers T.N. Adelmeijer J. et al.Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity.Hepatology. 2006; 44: 53-61Crossref PubMed Scopus (437) Google Scholar Similarly, diminished liver-derived procoagulant factors, such as factors V, VII, and X, cause prolongation of the prothrombin time, but are significantly offset by diminished liver-derived anticoagulant factors, especially protein C.7Tripodi A. Primignani M. Lemma L. et al.Evidence that low protein C contributes to the procoagulant imbalance in cirrhosis.J Hepatol. 2013; 59: 265-270Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar Moreover, elevated endothelial-derived factor VIII, coupled with low protein C, contributes to a relatively hypercoagulable state.8Sinegre T. Duron C. Lecompte T. et al.Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis.J Thromb Haemost. 2018; 16: 1132-1140Crossref PubMed Scopus (39) Google Scholar These changes, together with relative venous stasis and endothelial injury (Virchow’s triad) contribute to the common development of PVT and occasional DVT in cirrhosis patients. These changes complicate pre-procedure prophylactic strategies. In short, hemostatic pathways in cirrhosis are often rebalanced in a precarious manner and these currents can tip in either direction. All currently available laboratory measures of hemostasis have significant limitations in liver disease patients and lack adequate prospective data, especially as pre-procedure risk measures. None account for variables such as volume status (portal-collateral pressure and flow), renal function, or endothelial dysfunction.9Rautou P.E. Bresson J. Sainte-Marie Y. et al.Abnormal plasma microparticles impair vasoconstrictor responses in patients with cirrhosis.Gastroenterology. 2012; 143: 166-176 e6Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar The international normalized ratio (INR) is the most problematic because of its entrenched but unfounded position in traditional medical teaching. The test is a mathematical manipulation of the prothrombin time and measures procoagulant factors I, II, V, VII and X, but does not measure the deficit of liver-derived anticoagulant factors, such as protein C. Moreover, the test is “normalized” against warfarin-treated patients based on the activity of an added commercially available thromboplastin reagent. This causes significant variation in the INR in cirrhosis between different hospitals, depending on which thromboplastin is used in the test.1Intagliata N.M. Argo C.K. Stine J.G. et al.Concepts in coagulation in liver disease: a summary of the 7th International Coagulation In Liver Disease Conference.Thromb Haemost. 2018; 118: 1491-1506Crossref PubMed Scopus (111) Google Scholar, 10Bellest L. Eschwege V. Poupon R. et al.A modified international normalized ratio as an effective way of prothrombin time standardization in hepatology.Hepatology. 2007; 46: 528-534Crossref PubMed Scopus (109) Google Scholar Furthermore, use of fresh frozen plasma to “correct” a prolonged INR in cirrhosis does not actually change thrombin production (factor II), but does exacerbate portal hypertension.2Joist J.H. AICF and DIC in liver cirrhosis: expressions of a hypercoagulable state.Am J Gastroenterol. 1999; 94: 2801-2803Crossref PubMed Google Scholar, 3Rijken D.C. Kock E.L. Guimaraes A.H. et al.Evidence for an enhanced fibrinolytic capacity in cirrhosis as measured with two different global fibrinolysis tests.J Thromb Haemost. 2012; 10: 2116-2122Crossref PubMed Scopus (67) Google Scholar, 11Tripodi A. Chantarangkul V. Primignani M. et al.Thrombin generation in plasma from patients with cirrhosis supplemented with normal plasma: considerations on the efficacy of treatment with fresh-frozen plasma.Intern Emerg Med. 2012; 7: 139-144Crossref PubMed Scopus (72) Google Scholar, 12Giannini E.G. Stravitz R.T. Caldwell S.H. Correction of hemostatic abnormalities and portal pressure variations in patients with cirrhosis.Hepatology. 2014; 60: 1442Crossref PubMed Scopus (33) Google Scholar Platelet-level manipulation is the other mainstay of traditional teaching. The convergence of retrospective and in vitro studies regarding platelet levels in the 50,000–60,000 range as promoting thrombin generation has led to this range becoming the target for prophylaxis.1Intagliata N.M. Argo C.K. Stine J.G. et al.Concepts in coagulation in liver disease: a summary of the 7th International Coagulation In Liver Disease Conference.Thromb Haemost. 2018; 118: 1491-1506Crossref PubMed Scopus (111) Google Scholar, 2Joist J.H. AICF and DIC in liver cirrhosis: expressions of a hypercoagulable state.Am J Gastroenterol. 1999; 94: 2801-2803Crossref PubMed Google Scholar, 13Rockey D.C. Caldwell S.H. Goodman Z.D. et al.Liver biopsy.Hepatology. 2009; 49: 1017-1044Crossref PubMed Scopus (1507) Google Scholar, 14Giannini E.G. Greco A. Marenco S. et al.Incidence of bleeding following invasive procedures in patients with thrombocytopenia and advanced liver disease.Clin Gastroenterol Hepatol. 2010; 8 (quiz e109): 899-902Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar However, elevated vWF (see above) and increased circulating activated platelets in cirrhosis are mitigating conditions that have not been taken into consideration.4Hugenholtz G.C. Macrae F. Adelmeijer J. et al.Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen.J Thromb Haemost. 2016; 14: 1054-1066Crossref PubMed Scopus (86) Google Scholar, 15Raparelli V. Basili S. Carnevale R. et al.Low-grade endotoxemia and platelet activation in cirrhosis.Hepatology. 2017; 65: 571-581Crossref PubMed Scopus (73) Google Scholar When increased platelet levels are deemed urgently necessary, single-donor platelet transfusion will minimize immunologic risk. Thrombocytopenia in cirrhosis is multifactorial, involving shortened platelet survival, platelet sequestration, and/or inadequate bone marrow response. The lifespan of a normal platelet is approximately 10 days and one-third are sequestered in the spleen.16Daly M.E. Determinants of platelet count in humans.Haematologica. 2011; 96: 10-13Crossref PubMed Scopus (79) Google Scholar The half-life of transfused platelets has been reported to be as low as 2.5–4.5 days,17Cesar J.M. Vecino A.M. Survival and function of transfused platelets. Studies in two patients with congenital deficiencies of platelet membrane glycoproteins.Platelets. 2009; 20: 158-162Crossref PubMed Scopus (15) Google Scholar and their function is diminished.18Getz T.M. Turgeon A. Wagner S.J. Sodium citrate contributes to the platelet storage lesion.Transfusion. 2019 Feb 22; ([Epub ahead of print])Crossref Scopus (9) Google Scholar As a result, when procedures are planned in advance, recently approved TPO agonists are a nice alternative to platelet transfusion.19Terrault N.A. Hassanein T. Howell C.D. et al.Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure.J Hepatol. 2014; 61: 1253-1259Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 20Terrault N. Chen Y.C. Izumi N. et al.Avatrombopag before procedures reduces need for platelet transfusion in patients with chronic liver disease and thrombocytopenia.Gastroenterology. 2018; 155: 705-718Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 21Tateishi R. Seike M. Kudo M. et al.A randomized controlled trial of lusutrombopag in Japanese patients with chronic liver disease undergoing radiofrequency ablation.J Gastroenterol. 2019; 54: 171-181Crossref PubMed Scopus (58) Google Scholar TPO agonists have the advantage of not increasing portal pressure and elevating platelets for longer than transfusions can; however, eltrombopag has been associated with PVT when platelets inadvertently increased dramatically in a minority of patients.22Afdhal N.H. Giannini E.G. Tayyab G. et al.Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia.N Engl J Med. 2012; 367: 716-724Crossref PubMed Scopus (226) Google Scholar Both avatrombopag and lusutrombopag have more modest effects on platelet levels and, when used for a short duration, have not had this issue in currently available clinical trials.19Terrault N.A. Hassanein T. Howell C.D. et al.Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure.J Hepatol. 2014; 61: 1253-1259Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 20Terrault N. Chen Y.C. Izumi N. et al.Avatrombopag before procedures reduces need for platelet transfusion in patients with chronic liver disease and thrombocytopenia.Gastroenterology. 2018; 155: 705-718Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 21Tateishi R. Seike M. Kudo M. et al.A randomized controlled trial of lusutrombopag in Japanese patients with chronic liver disease undergoing radiofrequency ablation.J Gastroenterol. 2019; 54: 171-181Crossref PubMed Scopus (58) Google Scholar Dosing, duration of use, and expected platelet increases are depicted in Figure 2. Recently, fibrinogen levels have emerged as potentially more meaningful than INR to couple with platelet levels as a measure of bleeding risk, although target levels (usually 120–150 mg/dL) have to be conjectured from trauma literature.23Drolz A. Horvatits T. Roedl K. et al.Coagulation parameters and major bleeding in critically ill patients with cirrhosis.Hepatology. 2016; 64: 556-568Crossref PubMed Scopus (117) Google Scholar, 24Bolliger D. Szlam F. Molinaro R.J. et al.Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model.Br J Anaesth. 2009; 102: 793-799Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar When repletion of fibrinogen is desired, cryoprecipitate can be used, and because it is contained in a smaller volume than fresh frozen plasma, will have less of an impact on portal hypertension. Ninety-eight percent of fibrinogen is synthesized in the liver, and its half-life is approximately 4 days in healthy individuals,25Coleman M. Finlayson N. Bettigole R.E. et al.Fibrinogen survival in cirrhosis: improvement by “low dose” heparin.Ann Intern Med. 1975; 83: 79-81Crossref PubMed Scopus (35) Google Scholar which is shortened in cirrhosis.26Tennent G.A. Brennan S.O. Stangou A.J. et al.Human plasma fibrinogen is synthesized in the liver.Blood. 2007; 109: 1971-1974Crossref PubMed Scopus (202) Google Scholar Alternative means of assessing hemostatic pathways in cirrhosis have been investigated as potentially more reliable. The thrombin generation assay or endogenous thrombin production test has been instrumental in advancing our understanding of hemostatic pathways in cirrhosis, but seems unlikely to translate into a viable clinical tool, although the field is evolving rapidly. Whole blood tests are collectively known as “viscoelastic elastic tests” (including thromboelastography [TEG], rotational thromboelastometry [ROTEM], and sonorheometry), and they offer potentially better means of simulating the in vivo activity of the hemostatic pathways.27Davis J.P.E. Northup P.G. Caldwell S.H. et al.Viscoelastic testing in liver disease.Ann Hepatol. 2018; 17: 205-213Crossref PubMed Scopus (32) Google Scholar These tests depend on changes in a “resistance to motion” measure (TEG, ROTEM) or ultrasound density (sonorheometry) that detect thickness of an evolving clot. Using a small cuvette of whole blood, both ROTEM and TEG transduce resistance to stirring, as soluble factors become insoluble fibrin/platelet/red blood cell clot and then decreased resistance as a clot undergoes plasmin-driven dissolution (ie, lysis of the fibrin clot). The reactions can be run with various clot stimulators and additives to focus on different aspects of clot formation and dissolution. Thus, reports often show several “channels” wherein one may show the trace with inhibitors of platelets or fibrinolysis, for example. Although more physiologic than conventional tests, nuances of technique are unresolved (duration of the trace and stimulators) and the tests themselves remain without well-defined parameters in cirrhosis patients, thus requiring subjective interpretation of complex data. The most consistent utility in the published literature in cirrhosis has been the demonstration of intact clotting mechanisms, despite abnormal conventional indices, thus avoiding unnecessary plasma use.28De Pietri L. Bianchini M. Montalti R. et al.Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: a randomized, controlled trial.Hepatology. 2016; 63: 566-573Crossref PubMed Scopus (252) Google Scholar Several common procedures do not routinely require coagulation assessment in patients with cirrhosis before their performance, and include diagnostic and therapeutic paracentesis, common forms of thoracentesis, upper endoscopy to screen for and band esophageal varices, and diagnostic (but not therapeutic) colonoscopy29Runyon B.A. Aasld Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012.Hepatology. 2013; 57: 1651-1653Crossref PubMed Scopus (505) Google Scholar, 30Garcia-Tsao G. Abraldes J.G. Berzigotti A. et al.Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases.Hepatology. 2017; 65: 310-335Crossref PubMed Scopus (1055) Google Scholar, 31Hibbert R.M. Atwell T.D. Lekah A. et al.Safety of ultrasound-guided thoracentesis in patients with abnormal preprocedural coagulation parameters.Chest. 2013; 144: 456-463Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar (risk levels for procedures defined in Intagliata et al1Intagliata N.M. Argo C.K. Stine J.G. et al.Concepts in coagulation in liver disease: a summary of the 7th International Coagulation In Liver Disease Conference.Thromb Haemost. 2018; 118: 1491-1506Crossref PubMed Scopus (111) Google Scholar). Paracentesis and thoracentesis have a large body of data, including American Association for the Study of Liver Diseases guidelines, supporting the low risk of bleeding, even in patients with a combined elevation in INR and thrombocytopenia, and therefore the risks of transfusion greatly outweigh the potential benefit.29Runyon B.A. Aasld Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012.Hepatology. 2013; 57: 1651-1653Crossref PubMed Scopus (505) Google Scholar, 31Hibbert R.M. Atwell T.D. Lekah A. et al.Safety of ultrasound-guided thoracentesis in patients with abnormal preprocedural coagulation parameters.Chest. 2013; 144: 456-463Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar This does not apply to pharmacologically anticoagulated and renal failure patients, who may be at increased risk for bleeding from these proceedures.32Hung A. Garcia-Tsao G. Acute kidney injury, but not sepsis, is associated with higher procedure-related bleeding in patients with decompensated cirrhosis.Liver Int. 2018; 38: 1437-1441Crossref PubMed Scopus (36) Google Scholar Despite the shortcomings of measuring platelet count and fibrinogen level, they are the standard of care assessment of coagulation for all patients with cirrhosis when determination of values is indicated before a procedure (Table 1). Within the existing limitations, it is clear that assessment and prophylactic measures need to be individualized and are best emerging from discussion among care providers, the patient, and the team conducting an intervention. The most important point to be considered is to avoid those prophylactic measures, which offer only risk without benefit.Table 1Key Interventions in Procedural Bleeding Risk Mitigation, Thrombotic Complications in Cirrhosis, and Active BleedingBleeding prophylaxisaThe need for prophylactic measures depends on procedure risk assessment. In general, minor procedures like paracentesis/thoracentesis and upper endoscopy with banding do not require prophylaxis, although the authors recognize that risk assessment will vary in the clinical context. A consensus review of common procedure risks is available from Intagliata et al.1CommentAnticoagulant therapyCommentActive bleedingCommentPlatelets ≥50,000 by infusion or with TPO agonist if electiveWhether or not to recheck platelets is debated but recommended when bleeding risk is assessed as greater than minimal.aThe need for prophylactic measures depends on procedure risk assessment. In general, minor procedures like paracentesis/thoracentesis and upper endoscopy with banding do not require prophylaxis, although the authors recognize that risk assessment will vary in the clinical context. A consensus review of common procedure risks is available from Intagliata et al.1Acute setting such as new (especially if symptomatic) PVT or extension of prior thrombosis.Systemic anticoagulation with IV heparin or LMWH. Note, asymptomatic incidentally discovered PVT does not invariably warrant therapy. Spontaneous resolution may occur, especially if partial.Portal hypertension–relatedAnti-portal hypertension interventions, minimize volume expansion and blood product transfusions due to effects on portal pressure.Fibrinogen ≥120 mg/dLBest achieved with cryoprecipitate. Weight-based dose usually raises fibrinogen level by 50 mg/dL.Chronic PVT especially in patients listed for transplantation or history of symptomatic PVT or mesenteric thrombosis.DOACs are reported as safe and effective in Child–Pugh class A and early class B. Vitamin K antagonists (eg, warfarin) extensively reported but problematic due to uncertainty of target INR.Wound or mucosal oozing suspicious for AIC or hyperfibrinolysisPlatelets to ≥50,000, fibrinogen ≥120 mg/dL, Consider anti-fibrinolytic agent (aminocaproic acid or tranexamic acid).bAnti-fibrinolytic agents are not generally thought to induce a prothrombotic state, but can be problematic with pre-existing pathologic thrombus, such as PVT. The role of other agents like prothrombin complex concentrate are not yet defined.Control infectionActive infection may cause release of endothelial-derived “heparinoids,” which can have an anticoagulant effect.DVT prophylaxis in hospi