Thrombotic Thrombocytopenic Purpura Associated with Interferon alpha for the Treatment of Chronic Hepatitis C

Abstract

Purpose: Thrombotic thrombocytopenic purpura (TTP) is a rare entity characterized by microangiopathic hemolytic anemia, thrombocytopenia and symptoms consisting of fever, neurologic, or renal dysfunction. Development of TTP has been reported in relationship with many drugs. We report a rare case of TTP associated with use of interferon alpha (INF-alpha) for the treatment of chronic hepatitis C. Methods: A 48-year-old female was diagnosed with hepatitis C eleven months ago. Liver biopsy revealed chronic hepatitis (grade 1 stage 0), and genotype of 1B. Treatment with INF and ribavarin was initiated six months ago. At the end of 24th week of treatment, she presented to the clinic with extensive bruising over both extremities. Laboratory data revealed hemoglobin of 8.9 g/dL, platelet count of 15 K/UL, blood urea nitrogen of 19 mg/dL, serum creatinine of 1.1 mg/dL, total bilirubin of 1.8 mg/dL, unconjugated bilirubin of 1.6 mg/dL, presence of > 1 schistocytes/hpf, negative Coombs, Lactate dehydrogenase (LDH) of 1050 U/dL, haptoglobulin of < 8 U/dL, and negative anti nuclear antibody and cryoglobulins. A clinical diagnosis of TTP was made based on presence of microangiopathic hemolytic anemia and non-immune mediated thrombocytopenia. Interferon treatment was stopped and patient was started on plasmapheresis. At the end of 8th treatment with plasmapheresis, platelets increased to 184 K/UL and LDH decreased to 200 U/dL. ADAMTS13 assay revealed decreased activity to 5% in presence of an inhibitor. Thrombocytopenia was resolved without any clinical sequelae. Results: Chronic acquired thrombocytopenia is seen in about 5–35% of patients with hepatitis C virus infection. The proposed mechanisms include direct infection by HCV of megakaryocyte lineage and/or dysregulation of the host immune system. However, thrombocytopenia may also be induced by INF-alpha therapy of chronic hepatitis C. In most cases, INF-alpha induced thrombocytopenia results from bone marrow suppression. A second rare cause of INF-induced thrombocytopenia is the development of autoimmune thrombocytopenia. Few case reports have associated TTP with INF- alpha use. Although the mechanism of this occurrence is unknown, it may involve a secondary release of cytokines, with perturbation of the immune system, or direct endothelial immunomodulating activities of INF. Conclusions: TTP should be considered in differential diagnosis of thrombocytopenia in patients with hepatitis C treated with interferon.