Haemostatic alterations in patients with cirrhosis and hepatocellular carcinoma: laboratory evidence and clinical implications

Abstract

Venous thrombosis is a frequent complication in cancer and is associated with high morbidity and mortality. Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer‐related death worldwide, and it is associated with preexisting cirrhosis in 90% of cases. Patients with cirrhosis acquire complex alterations in their haemostatic system that may predispose them to bleed or thrombotic complications. There is growing evidence that HCC may tilt the haemostatic equilibrium in cirrhosis towards hypercoagulability, thus increasing the risk of venous thrombosis. Previously described mechanisms of HCC‐driven thrombophilia include thrombocytosis and increased platelet activation/function, increased fibrinogen concentration/polymerization, enhanced thrombin generation, hypofibrinolysis, and release of tissue factor‐expressing microvesicles. Nevertheless, there are currently no specific guidelines on risk stratification and management of thromboprophylaxis in patients with cirrhosis and HCC. Our review endeavours to summarize the latest findings on epidemiology, risk factors and pathogenesis of non‐malignant venous thrombosis in patients with cirrhosis and HCC, and provide evidence in support of tailored management of thrombotic risk in these patients.

Global hemostatic profiling in patients with decompensated cirrhosis and bacterial infections

“…These exclusion criteria were chosen to mitigate the effects of potential confounders on the assessment of hemostasis. [23] , [24] , [25] , [26] , [27] , [28] …”

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

“…A meta‐analysis of 11 studies (including both in‐ and outpatient populations) reported an increased risk of VTE with an OR of 1.7 (95% CI 1.3–2.2) associated with cirrhosis 18 . Patients with cirrhosis and hepatocellular carcinoma are at additional risk of VTE 19 with a cumulative incidence of 6% in a single‐center study, which reported hepatocellular carcinoma, multiple lesions, and distant metastases as independently associated with VTE 20 . VTE is associated with increased length of hospital stay and mortality in patients with cirrhosis 12,20,21 …”

Portal Vein Thrombosis in the Setting of Cirrhosis: A Comprehensive Review

“…Other factors that may induce blood hypercoagulability in patients with cirrhosis are systemic inflammation, a well-recognized feature of decompensated cirrhosis [ 51 ], and HCC [ 52 ]. The former is scarcely studied with contradictory results [ 24 , 28 ].…”

“…No information in this matter was provided in the long-term albumin administration trials [ 54 , 55 ]. As far as HCC is concerned, there is growing evidence suggesting that it is associated with pro-thrombotic alterations (i.e., increased platelet activation and function, enhanced thrombin generation, hypo-fibrinolysis, and elevated levels of prothrombotic microvesicles) that may synergistically contribute to hypercoagulability and thrombosis [ 52 ].…”