Thromboprophylaxis for venous thromboembolism prevention in hospitalized patients with cirrhosis: Guidance from the SSC of the ISTH

Abstract

Hospital‐associated venous thromboembolism (HA‐VTE) is a major cause of morbidity and mortality and is internationally recognized as a significant patient safety issue. While cirrhosis was traditionally considered to predispose to bleeding, these patients are also at an increased risk of VTE, with an associated increase in mortality. Hospitalization rates of patients with cirrhosis are increasing, and decisions regarding thromboprophylaxis are complex due to the uncertain balance between thrombosis and bleeding risk. This is further accentuated by derangements of hemostasis in patients with cirrhosis that are often considered contraindications to pharmacological thromboprophylaxis. Due to the strict inclusion and exclusion criteria of seminal studies of VTE risk assessment and thromboprophylaxis, there is limited data to guide decision making in this patient group. This guidance document reviews the incidence and risk factors for HA‐VTE in patients with cirrhosis, outlines evidence to inform the use of thromboprophylaxis, and provides pragmatic recommendations on VTE prevention for hospitalized patients with cirrhosis. In brief, in hospitalized patients with cirrhosis: We suggest inclusion of portal vein thrombosis as a distinct clinically important endpoint for future studies. We recommend against the use of thrombocytopenia and/or prolongation of prothrombin time/international normalized ratio as absolute contraindications to anticoagulant thromboprophylaxis. We suggest anticoagulant thromboprophylaxis in line with local protocols and suggest low molecular weight heparin (LMWH) or fondaparinux over unfractionated heparin (UFH). In renal impairment, we suggest LMWH over UFH. For critically ill patients, we suggest case‐by‐case consideration of thromboprophylaxis. We recommend research to refine VTE risk stratification, and to establish the optimal dosing and duration of thromboprophylaxis.

Outcome of pharmacological thromboprophylaxis in hospitalized patients with cirrhosis – a systematic review and meta-analysis

“…The present meta-analysis did not show the benefit of anticoagulation in reducing the incidence of VTE in hospitalized patients with cirrhosis. The International Society on Thrombosis and Haemostasis (ISTH) guidance suggests the use of pharmacological thromboprophylaxis in patients with cirrhosis in line with local protocols and not for all patients [34]. They preferred the use of LMWH or fondaparinux over UFH.…”

Prevention of Venous Thromboembolism in Medical Patients with Thrombocytopenia or with Platelet Dysfunction: The Last 10 Years

“…Hospitalization rates of patients with liver cirrhosis due to decompensating events, and for the management of comorbid diseases, are increasing. 29 Patients with cirrhosis may be at risk of both thrombotic and hemorrhagic events. Clotting abnormalities caused by lowered synthesis of the vitamin K–dependent clotting factors with prolongations in the prothrombin time (PT) and activated partial thromboplastin time (aPTT) and decreased plasma fibrinogen are common in patients with advanced liver disease, and, together with the low platelet counts, sustain the common perception of patients with cirrhosis as having primarily a high risk of bleeding.…”

“…Thus, according to the 2022 guidance from the SSC of the ISTH, 29 thrombocytopenia and prolongation of PT/international normalized ratio (INR) are not absolute contraindications to anticoagulant thromboprophylaxis. Anticoagulant thromboprophylaxis is thus suggested in line with local protocols, and LMWH or fondaparinux is preferred over UFH.…”

“…Anticoagulant thromboprophylaxis is thus suggested in line with local protocols, and LMWH or fondaparinux is preferred over UFH. 29 Mild (75,000/mm 3 to 150,000/mm 3 ) or moderate thrombocytopenia (50,000/mm 3 to 75,000/mm 3 ), that may be present in 13% of cirrhotic patients, does not interfere with prophylaxis and treatment decisions. However, a negligible risk of spontaneous bleedings has been documented for invasive procedures (endoscopic procedures, biopsy, and dental extractions) in patients with chronic liver disease and platelet counts ≥ 50,000/mm 3 .…”

Limitations of venous thromboembolism risk assessment models in medical patients: Response to “Unmet definitions in thromboprophylaxis for hospitalized medical patients: An appraisal for the need of recommendation”

“…Many high-risk patients, such as those who are obese or have chronic kidney or liver disease, are either not recorded or are underrepresented in original studies [ 12 ]. The 2022 International Society on Thrombosis and Haemostasis guideline concurred that there is insufficient evidence to support the use of VTE RAMs to guide thromboprophylaxis in hospitalized patients with cirrhosis [ 13 ].…”