Nr. 20(4)/2012

Delia Dima, Ioana Codruța Frinc, Mariana Pațiu, Andrei Cucuianu

Thrombotic thrombocytopenic purpura (TTP) is caused in a majority of cases by auto-antibodies that inhibit the von Willebrand factor (vWF) multimer cleaving enzyme (ADAMTS13); the abnormal persistence of these vWF multimers determines disseminated aggregation of platelets, leading to disseminated thrombosis as well as hemorrhage through platelet consumption. The natural history of the disease is severe, but with plasmapheresis followed by massive plasma transfusions (plasma exchange) and immunosuppressive treatment, TTP can be cured in a majority of cases. RL, 50 years old presented in December 2010, at the emergency room with confusion associated with headache. The neurological examination revealed confusion, bradylalia, without any focal signs. Clinical examination showed marked cutaneo-mucous pallor, hepatomegaly 4-5 cm and splenomegaly 3 cm under the costal margin. The hematological examination showed normocytic anemia (Hb 6 g/dl), moderate thrombocytopenia (28 x10^9/L), reticulocytosis (13%) and the presence of schizocytes. Biochemically there was indirect hyperbilirubinemia, mild hepatocytolysis, elevated lactatedehydrogenase (LDH) at 2637 U/L, normal renal function. Based on the clinical and hematological data, a diagnosis of TTP was established and treatment with plasma exchange (PEX) was urgently initiated in association with dexamethasone 16 mg/day and antiplatelet treatment with aspirin 75 mg/day. The response to PEX was prompt with rapid normalization of platelet count and reticulocytes, and the gradual disappearance of schizocytes. About 6 weeks later, after the reduction of the corticosteroid dose, concomitantly with an episode of acute enterocolitis with Klebsiella spp, followed by acute pneumonia with Enterococcus faecalis and Klebsiella pneumoniae, the platelet count dropped to 35x10^9/L, with reappearance of schizocytes on the blood smear and reticulocytosis. Dexamethasone 16 mg/day and PEX were resumed; vincristine and cyclophosphamide were also associated but no significant response was observed. We decided therefore to associate rituximab 375 mg/m2 (700 mg)/week. Four rituximab doses were administered, with a favourable outcome, with normalization of the platelet count and subsequent disappearance of schizocytes. Presently, the patient is in remission at 19 months after completing the treatment with rituximab. This case report illustrates the fact that in some TTP cases, classical treatment with plasma exchange and corticosteroids may not lead to lasting results. The association of B-cell specific immunosuppression anti-CD20 monoclonal antibodies (rituximab) may be an effective alternative

Keywords: thrombotic thrombocytopenic purpura,plasma exchange,rituximab,dexamethasone