Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura

Abstract

Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64–15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59–27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications.

Thrombotic thrombocytopenic purpura: Toward targeted therapy and precision medicine

“…iTTP is associated with an increased risk for other autoimmune diseases (mostly systemic lupus erythematosus and Sjögren's syndrome), which may present before, concomitant with, or after diagnosis of iTTP. The cumulative incidence of autoimmune disorders after iTTP diagnosis is 9.9% after 5 years, 13.5% after 10 years, and 25.9% after 12 years . The incidence is higher after rather than before the first iTTP episode and increases over time, suggesting a role for increasing age.…”

“…Of note, neither depression nor cognitive impairment was significantly associated with the occurrence of relapses or ADAMTS13 activity <10%‐20% during remission . Moreover, prevalence of hypertension and major depression is greater as is mortality among iTTP survivors in remission compared with a reference population . The excess of early death in patients with a history of iTTP remains unexplained and could result from sudden undiagnosed relapses, increased cardiovascular risk related to persistent severe ADAMTS13 deficiency, organ damage following the acute episode, or other causes …”

“…The cumulative incidence of autoimmune disorders after iTTP diagnosis is 9.9% after 5 years, 13.5% after 10 years, and 25.9% after 12 years. 50,51 The incidence is higher after rather than before the first iTTP episode and increases over time, suggesting a role for increasing age.…”

“…52 Moreover, prevalence of hypertension and major depression is greater as is mortality among iTTP survivors in remission compared with a reference population. 51 The excess of early death in patients with a history of iTTP remains unexplained and could result from sudden undiagnosed relapses, increased cardiovascular risk related to persistent severe ADAMTS13 deficiency, organ damage following the acute episode, or other causes. 50 When the clinical score suggests a low probability for ADAMTS13 activity <10%, it may be appropriate to withhold treatment for TTP; however the diagnosis of TTP cannot be excluded.…”

Additional autoimmune disorders in patients with acquired autoimmune thrombotic thrombocytopenic purpura

“…4 The French Thrombotic Microangiopathies (TMA) Reference Center has reported the same observation: 26 (10%) of 261 patients with acquired autoimmune TTP also had SLE. 5 The French TMA Center also documented the occurrence of 14 autoimmune disorders, in addition to SLE, among their TTP patients. Fifty-six (21%) patients had one or more of these 15 autoimmune disorders.…”