Thrombotic Thrombocytopenic Purpura: A Case Series from a Tertiary Care Centre in Northern India

Abstract: Thrombotic thrombocytopenic purpura is a medical emergency with varied clinical manifestations. High index of suspicion with careful evaluation of thrombocytopenia and hemolytic anemia is of paramount importance. Laboratory parameters of microangiopathic hemolytic anemia i.e. schitocytosis and increased LDH and indirect hyperbilirubinemia support the diagnosis. Plasma exchange is the treatment of choice. Post stem cell transplant TTP carries a poorer prognosis.

Introduction:

Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia associated with fever, renal dysfunction and neurological manifestations. Without treatment, TTP is almost uniformly fatal with a mortality rate approaching 90%. With the timely institution of therapeutic plasma exchange mortality decreases to about less than 10% (1). Recent reports indicate that rituximab can induce remission in the majority of patients with classic TTP (2). We report here 13 cases of TTP who were treated at our hospital in last 4 years. Six of these patients developed features of TTP post allogenic stem cell transplantation.

Materials and Methods: The study included retrospective analysis of patients who presented with the features of TTP. Patients with characteristic features of TTP included two or more features among the pentad commonly considered diagnostic of TTP. Evidence of microangiopathic hemolytic anemia and thrombocytopenia were the minimal requirement for the diagnosis with or without fever, renal dysfunction and neurological manifestations. Coagulation profile included prothrombin time and APTT. Liver and kidney function analysis was done in all patients. Response was assessed by clinical and laboratory parameters with monitoring platelet counts, LDH, and schistocytes in the peripheral blood film. Patients with LDH in normal range and platelet counts more than 100,000/µl were considered to have achieved remission.

Results: Patients with classic TTP recovered with plasma exchange and/or rituximab. Post-transplant TTP patients had a poorer prognosis as five out of six post-transplant TTP patients died.

Discussion: TTP can have a varied clinical presentation and can be associated with many other diseases. Our case series highlight the varied manifestations and associations of TTP and their management and outcome. TTP is a medical emergency and needs high index of suspicion for the diagnosis. In our series, TTP was diagnosed by the findings of thrombocytopenia and hemolytic anemia evidenced by presence of schistocytes in the peripheral blood film and increased LDH, in the absence of coagulopathy. TTP should be suspected in the presence of microangiopathic hemolytic anemia and thrombocytopenia (1,3), and treatment should be started immediately, as delay in treatment can increase the mortality (1). Plasma exchange has changed the prognosis of this highly fatal disease to a highly curable disease. Rituximab has further improved the management of TTP (2). Patients with classic TTP were treated with plasma exchange but 3 patients also required rituximab. All patients with classic TTP are in remission.

Transplant-associated microangiopathy (TAM) is a MAHA and thrombocytopenia that occurs after bone marrow transplantation. Patients with post-transplant TTP were diagnosed based on thrombocytopenia and features of microangiopathic hemolytic anemia with schistocytosis and raised LDH, in the absence of coagulopathy. They were treated with FFP and steroids, as plasma exchange is not beneficial for post-transplant TTP (1). Repeated plasma exchange with increased frequency and/or rituximab therapy are the agents of choice in relapsing disease (3). Rituximab is a safe and effective treatment for newly diagnosed TTP, and has been shown to decrease the number of plasma exchange required to achieve remission. We used rituximab in 3 patients and all improved. Post transplant MAHA carried poor prognosis.

Conclusion: Diagnosis of TTP requires a high index of suspicion and prompt treatment with plasma exchange, which results in a high cure rate. Rituximab is useful in patients relapsing or showing partial recovery. Plasma exchange has not been reported to be effective in post-transplant TTP.

Acknowledgment: We are thankful to Ms Bharti Sharma for compiling the data.

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