Thrombotic thrombocytopenic purpura following salvage chemotherapy with paclitaxel, ifosfamide and cisplatin in a patient with a refractory germ cell tumor: A case report and review of the literature

Abstract

Abstract. Thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy that is characterized by microvascular thrombosis, thrombocytopenia, hemolysis and end organ damage. An extensive variety of drugs, including certain chemotherapeutic agents, have been associated with TTP. However, paclitaxel, cisplatin and ifosfamide regimen (TIP)-induced TTP has not previously been described. The present study reports the case of a 43-year-old patient with a refractory testicular germ cell tumor who developed acute TTP during TIP chemotherapy. Following the third cycle of TIP chemotherapy, the patient developed fever, anemia, thrombocytopenia and confusion. A diagnosis of TTP was established. Plasmapheresis was initiated as daily treatment in the first week, then continued every other day for 4 weeks. TIP chemotherapy was discontinued. The patient's clinical and neurological symptoms improved markedly after a week. Renal function and hemolysis improved, and the patient was discharged in a stable condition. The patient did not develop any complications and has been in remission for 5 months. The Naranjo adverse drug reaction probability scale indicated a likely association between TTP and the TIP chemotherapy regimen in this patient. This case is also investigated with regard to the associated literature to increase the awareness of TTP following chemotherapy. IntroductionMoschowitz initially described thrombotic thrombocytopenic purpura (TTP) in 1925, characterized by hyaline thrombosis in a variety of tissues (1). The classic pentad of TTP characteristics, including microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fever, neurological findings and kidney function abnormalities, was described by Amorosi and Ultmann following a review of 16 cases in 1966 (2). TTP is a rare but emergent disease associated with increased mortality (3). The estimated incidence of TTP is 3.7 cases per million (3), and the mortality rate has been reported to range from 10-20% (4). The condition may be either inherited or acquired. The most common form of TTP is the acquired idiopathic form, characterized by an acute attack. Hemolytic uremic syndrome and TTP, which have similar clinicopathological features, are categorized as thrombotic microangiopathic diseases (5).It is essential to determine the underlying pathology of TTP in order to form a diagnosis and successfully manage the disease. This life-threatening disease may occur secondary to sepsis and malignancy in oncology cases (most likely stomach, colon and breast cancer, and adenocarcinoma cases) (6). An extensive variety of drugs, including certain chemotherapeutic agents, have been associated with TTP (7,8). Chemotherapy-associated TTP and thrombotic microangiopathy (TMA) are observed particularly with the use of mitomycin C, gemcitabine, cisplatin, bleomycin and oxaliplatin (9)(10)(11)(12)(13)(14). To the best of our knowledge, the present study is the first reported case of TTP in association with the paclitaxel, cisplatin and ifosfamide regimen (TIP)...

An Update in Drug-Induced Thrombotic Microangiopathy

“…Drug-induced TMA has been reported in children with acute lymphoblastic leukemia (34,35) and adults with solid tumors (36,37), receiving multiagent chemotherapy. Jodele et al described 13 patients developing TMA after high-dose chemotherapy and autologous stem cell transplantation for neuroblastoma (12 patients receiving carboplatin/etoposide/melphalan and one cyclophosphamide/thiotepa) (38).…”