1. 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

2. 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 (<100.000/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.

3.  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

4.  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

5. Romiplostim : action + side effect http://www.medscape.com Headache Arthralgia Myalgia Thrombotic events Thrombotic events

6.  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.

7. 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 2009.3 2010.6 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 50,000~100,000 2010.8 PLK 331,000

8. 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.

9. 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.