Diagnosis of Thrombotic Thrombocytopenic Purpura and Current Management

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening condition that is characterized by microangiopathic hemolytic anemia (MAHA), severe thrombocytopenia, and organ ischemia. A severe deficiency of ADAMTS13 (<10%) is the most specific biological marker of TTP and has recently been added to its definition. The estimated annual incidence of both immune thrombotic thrombocytopenic purpura (iTTP) and congenital thrombotic thrombocytopenic purpura together (cTTP) combined is two to six cases per million. There are two types of TTP, namely, congenital and acquired. cTTP is extremely rare, inherited in an autosomal pattern, and occurs due to either homozygous or compound heterozygous mutations of the ADAMTS13 gene (located on chromosome 9q34). This results in a deficiency of von Willebrand factor-cleaving metalloprotease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Immune TTP (iTTP) occurs due to autoantibodies (Abs) formed against ADAMTS13, resulting in a deficiency of ADAMTS13 (<10%). Over the years, understanding of TTP has evolved alongside advancements in diagnostic modalities and treatment strategies, which provide the basis for updates at various time points. This chapter on TTP provides an overview of its current definitions, pathogenesis, types, current diagnostic modalities, and treatment strategies. Newer treatment modalities like caplacizumab, rituximab, and plasma-cell-directed therapies have significantly improved the management of TTP by improving treatment outcomes and reducing morbidity. Consequently, we describe current guidelines and recommendations in detail, which would help in the prompt diagnosis and effective treatment of TTP.