THPO and hypersplenism: Platelet count in cirrhosis is reduced due to the following: (a) decreased production: impaired thrombopoietin synthesis by the liver results in reduced megakaryocyte stimulation; (b) increased clearance: hypersplenism due to portal hypertension accelerates platelet sequestration and destruction; and (c) immune activation: autoantibodies and immune complex-mediated platelet clearance further exacerbate thrombocytopenia.