Hepatocellular carcinoma (HCC) is characterized by a complex disruption of hemostatic balance, increasing the risk of both thrombotic and hemorrhagic events. Thrombotic complications, most notably portal vein thrombosis (PVT) and venous thromboembolism (VTE), have a significant impact on clinical outcomes and therapeutic strategies. Cirrhosis contributes to the precarious equilibrium between pro- and anticoagulant forces through impaired synthesis of coagulation factors, endothelial dysfunction, and systemic inflammation. In the presence of HCC tumor-driven mechanisms, such as tissue factor expression, extracellular vesicle release, platelet activation, and suppression of fibrinolysis exacerbate this prothrombotic state. In this scenario, advanced diagnostic tools such as thrombin generation assay (TGA) and rotational thromboelastometry (ROTEM) offer a more accurate assessment of coagulation dynamics than conventional tests, enabling better risk stratification especially for therapeutic purposes. Anticoagulant therapy has demonstrated clinical benefit in selected cases of non-malignant PVT and VTE, particularly when liver function is preserved. While prophylactic strategies are still under investigation, data suggest they may be safely implemented in selected surgical patients. In the setting of immunotherapy, especially regimens involving anti-VEGF agents, anticoagulation may be considered with careful management of bleeding risk due to portal hypertension. An individualized approach to anticoagulation, supported by functional coagulation testing, is gaining acceptance as a means to safely reduce thrombotic burden and potentially improve outcomes in patients with HCC.

Platelets are critical for hemostasis and play an active role in immune responses to infection. While thrombocytopenia in sepsis is associated with poor outcomes, platelet dysfunction remains less explored. This prospective observational pilot study investigated the relationship between platelet dysfunction and sepsis severity using multiple platelet function tests. Ten adults with sepsis or septic shock admitted to the ICU of “Fondazione Policlinico Universitario A. Gemelli” and seven healthy controls were enrolled. Blood samples were collected at admission (T0), after 48 h (T1), and after 7 days (T2). Controls were sampled only at T0. Besides platelet count, hemostatic platelet function was assessed by light transmission aggregometry (LTA), thromboelastography (TEG), and platelet activation markers (P-selectin and PAC-1 expression), whereas immune platelet function was assessed by investigation of platelet–leukocyte aggregates and soluble plasma levels of CD40L. Platelet function was correlated with procalcitonin levels and SOFA scores. While thrombocytopenia developed after 48 h, hemostatic and immune platelet dysfunctions were already evident at T0. Platelet function abnormalities were correlated with sepsis severity, as reflected by higher SOFA scores and elevated procalcitonin levels, particularly at T0. Early platelet dysfunction, preceding thrombocytopenia, may represent a potential early indicator of sepsis severity and support timely intervention for hemostatic and immune platelet-dependent abnormalities in septic patients.