Thrombotic thrombocytopenic purpura, genetic and secondary

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a clinical entity caused by deficiency of the ADAMTS13 protease, either due to hereditary deficiency or autoantibody formation. ADAMTS13 deficiency results in the persistence of ultralarge von Willibrand factor (vWF) multimers in the blood, which cling to the endothelial surface, resulting in the deposition of platelet-rich vaso-occlusive thrombi. Occlusion and mechanical shearing caused by these thrombi result in the clinical manifestations of thrombocytopenia, microangiopathic hemolytic anemia, renal injury, neurologic manifestations, and fever. TTP is an extremely rare disease, with incidence of approximately 3 per million people in adults, and 1 per 10 million in children. While mortality rates in the past reached as high as 90-100%, the advent of effective treatment, most notably with corticosteroids and plasma exchange therapy, has resulted in a significant improvement in outcomes, with survival rates of 70-90%.