A 61-year-old obese female with a history of cirrhosis due to non-alcoholic fatty liver disease presents to the hospital after a syncopal event at home. Echocardiography has revealed severe aortic stenosis, and she is being admitted to the cardiology service for further evaluation and consideration for aortic valve replacement. She denies any prodromal symptoms before this event, but does describe episodes of chest heaviness and exertional shortness of breath that have been taking place with increasing frequency over the past year. She does not have a history of coronary artery disease, and has never been evaluated by a cardiologist. On review of systems, she denies chest pain, palpitations or dyspnea. She has not had any recent illnesses, fevers, or chills, and she reports no past or current episodes of bright red blood per rectum, melena, or hemoptysis. The remainder of her review of systems is negative.
Recently, she underwent outpatient esophagogastroduodenoscopy (EGD), which revealed grade II esophageal varices, for which she now takes the non-selective beta-blocker, nadolol. She has never had ascites or hepatic encephalopathy.
The initial laboratory studies reveal a normal basic metabolic panel with creatinine 0.8 mg/dL. Her white blood cell count is 7 x 109/L, hemoglobin is 12 g/dL, and platelets are 95 x 109/L. Her aspartate aminotransferase (AST) is 45 IU/L, and alanine aminotransferase (ALT) is 57 IU/L. The remainder of the liver function testing is normal. Her international normalized ratio (INR) is 2.1.
Should this patient receive prophylactic anticoagulation at the time of hospital admission for the prevention of venous thromboembolism (VTE) while undergoing a cardiovascular evaluation for syncope?
Show Answer
The correct answer is: C. This patient is at elevated risk of venous thrombosis; therefore, cautious prophylactic anticoagulation with low molecular weight heparin (LMWH) is indicated.
Many physicians perceive patients with chronic liver disease to be protected from venous thrombosis because of "auto-anticoagulation" related to elevated prothrombin times and/or thrombocytopenia. However, it is now well established that patients with cirrhosis suffer from complex changes to the hemostatic system, rendering them at risk for both bleeding and thrombotic complications. Thrombotic complications within the venous system include PVT, deep vein thrombosis (DVT), and pulmonary embolism (PE). Several large epidemiological and population-based studies have demonstrated that patients with chronic liver diseases are not protected from venous thrombosis,1,2 but may in fact be at elevated risk,3 particularly for thrombosis within the portal venous system.4,5 This is especially true in patients with inherited thrombophilia.4,6
The relative hypercoagulable state observed in patients with cirrhosis is thought to result from increased levels of endothelial-derived procoagulants, including factor VIII and Von Willebrand factor, and reduced levels of protein C.7,8 This procoagulant imbalance has been confirmed in multiple independent studies,9,10 and suggests that these patients ought to be considered for antithrombotic prophylaxis in certain high-risk situations, such as major surgery or prolonged immobilization. This must be carefully balanced on a case-by-case basis, as patients with end-stage liver disease carry a significantly increased risk of bleeding. Evaluation of a patient's bleeding risk should not be based solely upon traditional markers of coagulation (prothrombin time, platelet count), as those results often misrepresent hypo- or hypercoagulability in this population.11,12 Instead, it is recommended that bleeding risk be assessed individually according to conditions known to increase risk of hemorrhage, namely portal hypertension and untreated varices, bacterial infection, renal failure, and endothelial dysfunction.13,16
Several recent, population-based analyses have demonstrated the safety and efficacy of prophylactic anticoagulation with unfractionated heparin (UFH) or LMWH for patients with cirrhosis who are at increased risk of VTE.17,20 Although current consensus guidelines do not specifically address VTE prophylaxis,21 expert consensus opinion favors cautious administration of VTE prophylaxis with LMWH or UFH in certain high-risk cirrhotic patients.22,23 In a recent systematic review, the authors concluded that there is currently enough evidence to make a case for careful prophylactic anticoagulation with LMWH in individual cirrhotics, provided that due consideration is given to variceal evaluation and prophylaxis with either endoscopic treatment and/or non-selective beta-blocker administration.24
This patient has stable, compensated chronic liver disease, and has recently undergone endoscopic evaluation that revealed no significant esophageal or gastric varices. Although she has abnormal coagulation parameters (elevated INR, reduced platelet count), she demonstrates none of the other risk factors that would significantly increase her risk of bleeding, namely bacterial infection, uremia, or severe portal hypertension. As her hospitalization will be associated with immobilization and possibly one or several high-risk procedures, she will be at significantly increased risk for the development of VTE. In her individual case, the risk of VTE outweighs the associated bleeding risk, and prophylactic anticoagulation with LMWH or UFH is indicated.
References
Dabbagh O, Oza A, Prakash S, Sunna R, Saettele TM. Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease. Chest 2010;137:1145-9.
Northup PG, McMahon MM, Ruhl AP, et al. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol 2006;101:1524-28; quiz 1680.
Sogaard KK, Horvath-Puho E, Gronbaek H, et al. Risk of venous thromboembolism in patients with liver disease: a nationwide population-based case-control study. Am J Gastroenterol 2009;104:96-101.
Amitrano L, Guardascione MA, Brancaccio V, et al. Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis. J Hepatol 2004;40:736-41.
Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med 2011;365:147-56.
Amitrano L, Brancaccio V, Guardascione MA, et al. Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis. Hepatology 2000;31:345-8.
Lisman T, Bongers TN, Adelmeijer J, et al. Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology 2006;44:53-61.
Tripodi A, Primignani M, Chantarangkul V, et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009;137:2105-11.
Delahousse B, Labat-Debelleix V, Decalonne L, et al. Comparative study of coagulation and thrombin generation in the portal and jugular plasma of patients with cirrhosis. Thromb Haemost. 2010;104:741-9.
Gatt A, Riddell A, Calvaruso V, et al. Enhanced thrombin generation in patients with cirrhosis-induced coagulopathy. J Thromb Haemost 2010;8:1994-2000.
Segal JB, Dzik WH. Transfusion Medicine/Hemostasis Clinical Trials N. Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review. Transfusion 2005;45:1413-25.
Vieira da Rocha EC, D'Amico EA, Caldwell SH, et al. A prospective study of conventional and expanded coagulation indices in predicting ulcer bleeding after variceal band ligation. Clin Gastroenterol Hepatol. 2009;7:988-93.
Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med. 2010;362:823-2.
de Franchis R, Baveno VF. Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2010;53:762-8.
Montalto P, Vlachogiannakos J, Cox DJ, et al. Bacterial infection in cirrhosis impairs coagulation by a heparin effect: a prospective study. J Hepatol 2002;37:463-70.
Noris M, Remuzzi G. Uremic bleeding: closing the circle after 30 years of controversies? Blood 1999;94:2569-74.
Intagliata NM, Henry ZH, Shah N, et al. Prophylactic anticoagulation for venous thromboembolism in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding. Liver International.r 2014;34:26-32.
Bechmann LP, Sichau M, Wichert M, et al. Low-molecular-weight heparin in patients with advanced cirrhosis. Liver Int 2011;31:75-82.
Villa E, Camma C, Marietta M, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012;143:1253-1260 e1251-4.
Aldawood A, Arabi Y, Aljumah A, Alsaadi A, Rishu A, Aldorzi H, et al. The incidence of venous thromboembolism and practice of deep venous thrombosis prophylaxis in hospitalized cirrhotic patients. Thromb J 2011;9:1.
Guyatt GH, Akl EA, Crowther M, et al. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:7S-47S.
Kanaan AO, Silva MA, Donovan JL, Roy T, Al-Homsi AS. Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients. Clin Ther 2007;29:2395-405.
Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e195S-226S.
Aggarwal A, Puri K, Liangpunsakul S. Deep vein thrombosis and pulmonary embolism in cirrhotic patients: systematic review. World J Garstroenterol 2014;20:5737-45.
Log in to MyACC
