Caplacizumab As Step-Up Therapy In Refractory Ttp Utilizing Adamts-13 Activity And Evidence Of End-Organ Damage

Background: Thrombotic Thrombocytopenic Purpura (TTP) is a form of microangiopathic hemolytic anemia that is classically characterized by the clinical pentad of fever, hemolytic anemia, thrombocytopenia, renal dysfunction, and neurologic dysfunction. The pathophysiology of acquired TTP is marked by autoantibody formation against ADAMSTS13, an enzyme responsible for breaking down von Willebrand Factor (vWF) multimers. Standard therapy for TTP includes both replenishing functional ADAMTS-13 and immune-modulation with plasma-exchange and steroids/rituximab, respectively. A novel therapy addresses the microvascular thrombosis hallmark of end-organ damage in TTP. Caplacizumab, a humanized immune globulin that inhibits vWF interaction with platelets, achieved its primary endpoint of faster time to platelet normalization than placebo in the Stage 3 HERCULES trial when given up-front with additional standard therapies.