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.

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iTTP survivors experience high rates of adverse health sequelae and increased mortality over long-term follow up. We conducted this multi-center cohort study to evaluate long-term mortality and causes of death in iTTP survivors. Between 2003 and 2020, 222 patients were enrolled in the Ohio State University and Johns Hopkins TTP registries and followed for a median of 4.5 (interquartile range [IQR],75 0.4-11.5) years. Nine patients died during their first iTTP episode and 29 patients died during follow-up. Mortality rate was 1.8 times higher than expected from an age, sex and race adjusted reference population. Cardiovascular disease was a leading primary cause of death (27.6%) tied with relapsed iTTP (27.6%), followed by malignancy (20.7%), infection (13.8%), and other causes (10.3%). Male sex [HR 3.74 (95% CI 1.65-8.48, P=0.002), increasing age [HR 1.04 (95% CI 1.01-1.07), P=0.011] and number of iTTP episodes [HR 1.10 (95% CI 1.01-1.20), P=0.022] were associated with mortality in a model adjusted for African American race [HR 0.70 (95% CI 0.30-1.65), P=0.702], hypertension [HR 0.47 (95% CI 0.20-1.08), P=0.076], CKD [HR 1.46 (95% CI 0.65-3.30, P=0.358] and site [HR 1.46 (95% CI 0.64-3.30), P=0.358]. There was a trend towards shorter survival in patients with lower ADAMTS13 activity during remission (P=0.078). In conclusion, iTTP survivors are at higher risk of death compared with a reference population and cardiovascular disease is a leading cause of death. Our study highlights the need for survivorship care, and investigation focused on cardiovascular disease and early mortality in TTP survivors.

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