These include: 1) sequestration of platelets in the enlarged spleen secondary to portal hypertension (hyper-splenism); 2) reduced hepatic production of thrombopoietin; 3) bone marrow suppression by HCV or antiviral treatment; and 4) increased platelet destruction mediated by immune mechanisms involving anti-platelet autoantibodies and platelet-associated immune complexes. This evidence concerns the gene THPO and portal hypertension.