Chapter 27 - Thrombotic thrombocytopenic purpura

Abstract

Thrombotic thrombocytopenic purpura (TTP), also known as Moschcowitz disease, is a rare and fatal thrombotic microangiopathy (TMA) characterized by microangiopathic hemolytic anemia (MAHA), severe thrombocytopenia and a variable degree of organ ischemia linked to disseminated microvascular platelet-rich thrombi, particularly affecting the brain and heart. The underlying mechanism is the severe ADAMTS13 activity deficiency, which results in ULVWF being uncleaved, leading to the TTP clinical presentation. TTP is mostly acquired due to ADAMTS13 autoantibodies, inhibiting ADAMTS13 or increasing its clearance (immune-mediated TTP, iTTP). However, it is rarely inherited owing to mutations in ADAMTS13 (congenital TTP, cTTP). Acute TTP was universally life-threatening until therapeutic plasma therapy (TPE) was introduced, which improved the mortality rate from 80%–90% to 10%–20%. Rapid recognition and timely diagnosis to initiate appropriate treatment are crucial but challenging, because TTP shares many clinical presentations with other disorders (including pregnancy-related syndromes, hemolytic uremic syndrome, and other TMAs). Triple therapy with TPE, immunosuppressives (e.g., corticosteroids and rituximab), and caplacizumab is proposed as the standard care for acute iTTP. Additionally, novel anti-VWF therapies, recombinant ADAMTS13, and its potential antibody-resistant ADAMTS13 variants are under development.