ADAMTS13 Deficiency in the Immune and Hereditary Forms of Thrombotic Thrombocytopenic Purpura

Introduction: This review explores the role of ADAMTS13 deficiency in both immune-mediated and hereditary forms of Thrombotic Thrombocytopenic Purpura (TTP), a rare and life-threatening hematological disorder characterized by microvascular thrombosis and platelet consumption. Objective: The principal objective is to consolidate current knowledge on the pathophysiology, diagnosis, and therapeutic approaches to improve patient outcomes and inform future research. Methods: A literature review was conducted using PubMed, SciELO, Scopus, and the Virtual Health Library (BVS), covering publications from 1980 to 2024. The search used standardized descriptors related to platelet aggregation, von Willebrand Factor (vWF), TTP, and ADAMTS13. After screening, 27 articles were selected for a detailed analysis. Findings: TTP results from a severe deficiency in ADAMTS13, an enzyme that cleaves ultra-large vWF multimers, preventing spontaneous platelet aggregation. In hereditary cases, mutations in ADAMTS13 lead to its inactivity. In acquired forms, immune-mediated autoantibodies mainly inhibit or accelerate the clearance of ADAMTS13. Diagnosis is often delayed due to nonspecific clinical presentation but relies heavily on measuring ADAMTS13 activity and identifying inhibitory antibodies. Plasma exchange therapy is the current gold standard, combined with corticosteroids and, in some cases, immunosuppressants such as rituximab. Newer treatments, including recombinant ADAMTS13 and caplacizumab, are promising for refractory or relapsing cases. Discussion: Understanding ADAMTS13 deficiency has improved the diagnosis and treatment of TTP; however, current assays have limited sensitivity. While plasma exchange is effective, newer therapies, such as recombinant ADAMTS13 and caplacizumab, offer hope for refractory cases. These treatments may also reduce healthcare costs. Standardized diagnostics and access to advanced therapies are essential for better outcomes and equitable care.