Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and ischemic end organ injury due to microvascular platelet-rich thrombi. TTP results from a severe deficiency of the specific von Willebrand factor (VWF)-cleaving protease, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13). ADAMTS13 deficiency is most commonly acquired due to anti-ADAMTS13 autoantibodies. It can also be inherited in the congenital form as a result of biallelic mutations in the ADAMTS13 gene. In adults, the condition is most often immune-mediated (iTTP) whereas congenital TTP (cTTP) is often detected in childhood or during pregnancy. iTTP occurs more often in women and is potentially lethal without prompt recognition and treatment. Front-line therapy includes daily plasma exchange with fresh frozen plasma replacement and immunosuppression with corticosteroids. Immunosuppression targeting ADAMTS13 autoantibodies with the humanized anti-CD20 monoclonal antibody rituximab is frequently added to the initial therapy. If available, anti-VWF therapy with caplacizumab is also added to the front-line setting. While it is hypothesized that refractory TTP will be less common in the era of caplacizumab, in relapsed or refractory cases cyclosporine A, N-acetylcysteine, bortezomib, cyclophosphamide, vincristine, or splenectomy can be considered. Novel agents, such as recombinant ADAMTS13, are also currently under investigation and show promise for the treatment of TTP. Long-term follow-up after the acute episode is critical to monitor for relapse and to diagnose and manage chronic sequelae of this disease.

Thrombocytopenia and Intracranial Venous Sinus Thrombosis after “COVID-19 Vaccine AstraZeneca” Exposure

“…An immune-mediated thrombotic thrombocytopenic purpura (iTTP) was discussed [25], however, the ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13) enzyme activity was not significantly reduced in any of our three patients.…”

Prediction of Severity and Mortality in Acquired Thrombotic Thrombocytopenic Purpura (aTTP). Utility of Clinicalbiological Scores

“…Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening thrombotic microangiopathy (TMA) [1][2][3]. It has an average annual prevalence of approximately 10 cases/million people and an annual incidence between 1.5 and 6.0 cases per million according to studies conducted in France [4], the United States [5,6], the United Kingdom [7,8], and Spain [9].…”

“…The latter is rare and represents 2% of all aTTP cases [1]. Independently of its origin, the lack of ADAMTS13 activity (less than 10%) is the only biologic marker specific for aTTP and it is a crucial factor in the diagnosis [1,3].…”

“…However, none of these symptoms is exclusive to aTTP and they may be present in other pathologies such as hemolytic uremic syndrome (HUS), other TMA syndromes, and Evans syndrome [1,10]. For this reason, the presence of a severe deficiency of ADAMTS13 (<10% ADAMTS13 activity), although not required to start treatment, has become necessary to confirm the diagnosis [1,3]. The first-line therapy for acute aTTP is based on daily therapeutic plasma exchange (TPE) for ADAMTS13 deficiency in conjunction with steroids as an adjunct treatment due to the autoimmune nature of aTTP.…”

“…The first-line therapy for acute aTTP is based on daily therapeutic plasma exchange (TPE) for ADAMTS13 deficiency in conjunction with steroids as an adjunct treatment due to the autoimmune nature of aTTP. The use of a humanized anti-CD20 monoclonal antibody (rituximab) as part of the frontline treatment has been proposed lately, due to the high response rates, the shorter hospitalization periods, and the fewer relapses reported in some studies [3,11].…”