Current concepts in the diagnosis and management of thrombotic thrombocytopenic purpura. Nabhan C, Kwaan HC. Hematolology/oncology Clinics of North America 2003;17(1):177-199.

ABSTRACT:

Thrombotic thrombocytopenic purpura (TTP) is a multisystem disease characterized by thrombocytopenia, hemolytic anemia, renal failure, fever, and neurologic abnormalities. Plasma exchange (PE) has revolutionized the outcome of this entity from a once fatal disease to a disease that potentially is cured or has prolonged remission. The understanding of the pathophysiology of TTP continues to evolve. Recently, investigators showed that a deficiency in a specific plasma protease responsible for cleaving von Willebrand factor (vWf) plays a crucial role in the familial form of TTP. This explains in part why patients usually respond to PE therapy. The identification of a mutation in a specific gene that belongs to the metalloproteinase family could have important therapeutic implications. TTP can be induced by certain drugs, especially immunosuppressants, in the setting of bone marrow and solid organ transplantation. This disease also has been described in association with HIV, pregnancy, cancer, and chemotherapy. In addition, there is much overlap between TTP and hemolytic uremic syndrome (HUS) depending on its severity. A recent study of patients with thrombotic microangiopathy, including TTP and HUS, showed that the vWf-cleaving protease activity was deficient in TTP but not HUS. Patients with HUS have normal levels of protease without the presence of an inhibitor, explaining why few patients, if any, would benefit from PE therapy in that setting. The distinction between both entities is crucial in clinical practice, as PE has some morbidity and is costly. The incidence of TTP-HUS has risen, however, with 3% to 7% of patients infected with E. coli O157:H7 eventually progressing to an overt TTP-HUS. Early signs of TTP-HUS should be monitored and PE should be instituted promptly when identified. Despite its severity, investigators have shown that patients with Shiga toxin-associated TTP-HUS respond to PE with good outcomes. Treatment with antibiotics has no benefit and in fact has been shown recently to increase the incidence of TTP-HUS. The use of antimotility agents is also contraindicated. Currently, attempts are being made to block the Shiga-toxin receptor with synthetic analogues.