Thrombopoietin induces rapid resolution of thrombocytopenia after orthotopic liver transplantation through increased platelet production

Thrombopoietin (TPO) deficiency has been proposed as an important etiologic factor for thrombocytopenia in advanced-stage liver disease. To clarify th e contributions of platelet production, platelet consumption, coagulation a ctivation, and splenic sequestration to thrombocytopenia in liver disease, we studied TPO serum levels and markers of platelet production, platelet ac tivation, and coagulation activation before and 14 days after orthotopic li ver transplantation (OLT) in 18 patients with advanced liver cirrhosis. Thr ombocytopenia before transplantation occurred with low-normal serum levels of TPO, normal levels of platelet and coagulation activation markers, and n o increase in bone marrow production of platelets. TPO serum levels increas ed significantly on the first day after OLT, preceding the increase of reti culated platelets by 3 days and peripheral platelets by 5 days. Normalizati on of the peripheral platelet count occurred in most patients within 14 day s of OLT, irrespective of the change in spleen size assessed by computed to mography volumetry. Normalization of platelet counts was not hampered by a certain degree of platelet activation observed during the steepest increase in the peripheral platelet count. Bone marrow production of platelets incr eased significantly within 2 weeks of transplantation. Low TPO serum levels with low platelet counts and without platelet consumption suggests low TPO production in end-stage liver disease. The rapid increase in TPO serum lev els after transplantation induces an increase in the bone marrow production of platelets. Decreased TPO production in the cirrhotic fiver is an import ant etiologic factor for thrombocytopenia in liver disease that is rapidly reversed by transplantation. (C) 2000 by The American Society of Hematology.