Immune thrombotic thrombocytopenic purpura: Spotlight on long-term outcomes and survivorship

Abstract

Advances in diagnosis and treatment have dramatically improved survival of acute immune thrombotic thrombocytopenic purpura (iTTP) and iTTP has evolved from an acute fatal condition to a chronic relapsing disorder. In addition to the risk of iTTP relapse, iTTP survivors are at risk of multiple adverse health outcomes including higher than expected rates of all-cause mortality, increased rates of stroke and other cardiovascular disease, and higher rates of morbidities such as obesity, hypertension, and autoimmune disorders. iTTP survivors also report neurocognitive impairment, depression, and reduced quality of life. Women with iTTP are at risk for recurrent iTTP, preeclampsia, and other maternal and fetal complications in subsequent pregnancies. ADAMTS13 activity during clinical remission has emerged as an important targetable risk factor for iTTP relapse and other outcomes including stroke and all-cause mortality. This review summarizes current literature regarding the epidemiology and potential mechanisms for adverse long-term sequelae of iTTP, outlines current best practices in iTTP survivorship care, and highlights a research agenda to improve long-term iTTP outcomes.

Treatment Challenges of Acquired Thrombotic Thrombocytopenic Purpura in Pediatric Patients From a Low-Income Country

“…The primary approach for aTTP treatment involves performing PEX utilizing fresh frozen plasma and steroids, which is recognized as the initial therapeutic choice. A delayed commencement of plasma exchange has shown an association with a heightened early mortality rate, potentially stemming from misdiagnosis or insufficient access to treatment, similar to what was observed in our patient [ 11 - 13 ].…”

“…The employment of anti-CD20 (rituximab) in combination with PEX has exhibited favorable outcomes. Other immunosuppressive agents such as cyclosporin A, mycophenolate mofetil, or cyclophosphamide may offer potential benefits in refractory cases, which are characterized as situations where remission is not attained by the fifth day, similar to what was observed in the second case [ 11 - 13 , 15 , 16 ]. Supportive therapy also stands as a crucial component for aTTP pediatric patients, encompassing the administration of blood components and folic acid during hemolysis [ 13 , 15 - 19 ].…”

“…Following the 1960s, the earliest reports of TTP in pediatric patients began to surface. It was not until the late 1970s that the congenital deficiency of ADAMTS-13 was designated as Upshaw-Schulman syndrome [ 11 , 12 ].…”

“…Historically, aTTP diagnosis was established when patients manifested a pentad of fever, renal and neurological anomalies, TMA, and thrombocytopenia, although this pentad has become less prevalent in contemporary diagnosis [7][8][9]. At present, most patients demonstrate thrombocytopenia, TMA, and erythrocyte fragmentation in peripheral blood, coupled with negative direct Coombs testing and no deviations in coagulation times [10,11]. Initial analysis for suspected TMA should involve assessing ADAMTS-13 activity, with a marked deficiency in activity (<10%) confirming the diagnosis of thrombotic thrombocytopenic purpura (TTP).…”

Cardiovascular Disease and Stroke in Immune TTP–Challenges and Opportunities

“…Mortality of acute TTP episodes has reduced from >90% to <10% with rapid diagnosis and prompt treatment with plasma exchange and immunosuppression [ 3 , 4 ]. With a growing population of TTP survivors, immune-mediated TTP (iTTP) is recognized as a chronic disorder that requires long-term care [ 5 , 6 , 7 , 8 ]. Importantly, iTTP is a thrombotic vascular disorder, and thromboembolic events such as stroke are a leading cause of mortality and morbidity in acute iTTP [ 9 , 10 ].…”