PF805 INCIDENCE, CLINICAL FEATURES, RISK FACTORS AND OUTCOMES OF REFRACTORY ACQUIRED IMMUNE THROMBOTIC THROMBOCYTOPENIC PURPURA: A CHINESE MULTI‐CENTER EXPERIENCE
Authors: Gui R.‐Y. , Zhang G.‐C. , Wang C.‐C. , Liu X. , Cai X. , Wu J. , Huang Q.‐S. , Fang M.‐Y. , Yang C.‐M. , Zhang J.‐H. , Yang L.‐H. , Zhang J.‐Y. , Sun L. , Cheng Y.‐F. , Zhu Q.‐J. , Nie Y.‐L. , Mao M. , Huang X.‐J. , Zhang X.‐H. 
Published: June 2019

Background:Acquired immune thrombotic thrombocytopenic purpura(TTP) is an autoimmune disorder that is characterized by microangiopathic hemolytic anemia and thrombocytopenia with associated organ dysfunction. Refractory TTP that fails to respond to standard therapeutic plasma exchange(TPE) and prednisone continues to be associated with high mortality. Although recent evidence had identified age, renal involvement, and cardiac involvement as predictors of high mortality, little information is available on clinical factors capable of predicting the treatment response that may be able to guide the initiation of early and targeted aggressive therapy.Aims:To identify the incidence and early indicators of refractory TTP and risk factors of exacerbation, relapse and mortality.Methods:The study population consisted of all patients with clinically suspected TTP from 14 large academic medical centers in China from January 2005 to January 2018. We excluded patients who were diagnosed congenital TTP or other thrombotic microangiopathies. Final diagnosis of acquired immune TTP was confirmed by at least one senior hematologist. Data(demographic, clinical, laboratory and treatment information) obtained at diagnosis and prior to treatment were collected from electronic medical records. Stepwise regression was used to identify independent risk factors.Results:Among 261 patients referred to the 14 medical centers, 126 patients satisfied the inclusion criteria and were included in the analysis. Overall, 41/126 patients were regarded as having refractory TTP. Compared with those of the responsive group, the patients in the refractory group were older and had higher d‐dimer, C‐reactive protein(CRP) and serum creatinine levels and more acute kidney insufficiency. The ADAMTS13 levels were comparable between the two groups. In multivariate logistic analysis, we identified albumin<35 g/L(OR 3.939, 95% CI 1.050–14.782; p = 0.042) and CRP < 15 mg/L(OR 0.280, 95% CI 0.085–0.928, p = 0.037) as independent predictors of refractory TTP. All patients underwent a median of 5 TPE sessions, and corticosteroids were given to most of the patients. When combined with first‐line treatments, alternative treatments, such as intravenous immunoglobulin, rituximab, cyclosporine A and vincristine, each showed better outcomes, although the differences were not statistically significant. With a median follow‐up time of 1131 days, the 1‐year overall survival(OS) and progression‐free survival of all TTP patients were 74.1% and 60.3%, respectively. Refractory and responsive TTP had significantly different outcomes(p < 0.001). In the multivariate analysis, an older age(OR 1.082, 95% CI 1.017–1.151, p = 0.013), proteinuria(OR 13.628, 95% CI 1.406–132.072, p = 0.024) and increased indirect bilirubin(OR 1.067, 95% CI 1.022–1.114, p = 0.03) were independent risk factors of exacerbation/relapse, but exacerbation/relapse had no influence on OS(p = 0.566). Cox regression indicated that two factors were significantly associated with OS: age>45 years(HR 14.127, 95% CI 1.404–142.136, p = 0.025) and acute kidney insufficiency(HR 9.100, 95% CI 1.838–45.052, p = 0.007).Summary/Conclusion:This novel observation showed that 32.5% of TTP cases were refractory and that serum albumin and elevated CRP might be early predictors of these cases. These factors may have the potential to guide intensification of therapy and improve survival outcomes, which should be reevaluated in larger prospective studies.