Portal vein thrombosis as complication of romiplostim treatment in a cirrhotic patient with hepatitis C-associated immune thrombocytopenic purpura Journal of Hepatology, 2011 Medizinische Klinik, Klinikum der J.W. Goethe-Universität, Frankfurt am Main R2. Park sunhee/ Prof. Kim ByungHo

BACKGROUND  Chronic HCV infection is associated with a variety of extrahepatic manifestations –lymphoproliferative hematologic diseases –ITP  ITP –Primary ITP : de novo –Secondary ITP : d/t underlying conditions pharmacotherapy, autoimmune diseases, chronic viral infections including HCV –Characteristics thrombocytopenia (< /μl) due to formation of autoantibodies against platelet surface antigens –Pathophysiology exceeding platelet destruction, impair platelet production, relative thrombopoietin deficiency Liver disease : diminished further by exceeding sequestration of platelets in the enlarged spleen.

 The therapeutic strategy –determined by bleeding complications and platelet count ITP patients + PLK > 30,000/μl without bleeding complications : no therapy ITP patients + serious bleedings (requiring transfusion) : required treatment –First line therapy steroids acute bleeding : + iv immunglobulins –Second line therapy Splenectomy

 Newer approaches for refractory ITP therapy –Rituximab which alters B cell response and antibody formation and leads to a response in 30-50% of patients. –Agents that directly stimulate the thrombopoietin receptor Eltrombopag Romiplostim

Romiplostim : action + side effect Headache Arthralgia Myalgia Thrombotic events Thrombotic events

 There are indications that risk for development of portal vein thrombosis in patients with advanced liver cirrhosis might be increased under therapy with thrombopoietin receptor agonists.  We report a case of a patient with Child class B liver cirrhosis with concurrent immune thrombocytopenic purpura that developed portal vein thrombosis under therapy with the thrombopoietin receptor agonist, romiplostim.

IV heparin Romiplostim stop TRA (Romiplostim) For 9 mo Child B, MELD 16 Steroid Esophageal varix bleeding  Ligation  propranolol METHODS F/50 C-viral LC Child B ITP Adm MELD 20 Child B Adm MELD 20 Child B Abd sono Abd CT  Portal vein thrombosis Abd sono Abd CT  Portal vein thrombosis LT CASE REPORT PLK <20,000 PLK 50,000~100, PLK 331,000

RESULTS  The thrombotic event was assumed to be associated with romiplostim treatment for immune thrombocytopenic purpura via excessive elevation of platelet count.  After anticoagulation with heparin and cessation of romiplostim treatment, complete recanalisation of the portal vein was achieved.

CONCLUSION  Romiplostim should be used with precaution in patients with hepatitis C-associated immune thrombocytopenic purpura and advanced liver cirrhosis as the risk for thrombotic complications may increase significantly.