Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study

Summary Background Among the syndromes characterised by thrombotic microangiopathy, thrombotic thrombocytopenic purpurais distinguished by a severe deficiency in the ADAMTS13enzyme. Patients with this disorder need urgent treatment with plasma exchange. Because ADAMTS13activity testing typically requires prolonged turnaround timesand might be unavailable in resource-poor settings, a method to rapidly assess the likelihood of severe ADAMTS13deficiency is needed. Methods All consecutive adult patients presenting to three large academic medical centres in Boston, MA, USA, with thrombotic microangiopathyand a possible diagnosis of thrombotic thrombocytopenic purpurabetween Jan 8, 2004, and Dec 6, 2015, were included in an ongoing multi-institutional registry (the Harvard TMA Research Collaborative). Univariate analysis was used to identify covariates for a logistic regression model predictive of severe ADAMTS13deficiency (≤10% activity). A clinical point score was generated, and its diagnostic performance was assessed using internal and external validation cohorts and compared to clinical assessment alone. Findings 214 patients with thrombotic microangiopathywere included in the derivation cohort. A seven-component clinical prediction tool, termed the PLASMIC score, was developed and found to reliably assess the pretest probability of severe ADAMTS13deficiency ( C statistic 0·96, 95% CI 0·92–0·98). Our diagnostic model was reproducibly accurate in both the internal (0·95, 0·91–0·98) and external (0·91, 0·85–0·95) validation cohorts. The scoring system also more consistently diagnosed thrombotic microangiopathydue to severe ADAMTS13deficiency than did standard clinical assessment, as measured by C statistic (0·96, 95% CI 0·92–0·98 for PLASMIC vs 0·83, 0·77–0·88 for clinical assessment; p vs 0·111 for clinical assessment; mean paired difference 0·05, 95% CI 0·01–0·08; p Interpretation We have developed and validated a clinical prediction tool—the PLASMIC score—to stratify patients with thrombotic microangiopathyaccording to their risk of having severe ADAMTS13deficiency. We have shown that this scoring system is superior to standard clinical assessment in addressing the diagnostic challenge presented by thrombotic microangiopathy. Its use, together with clinical judgment, may facilitate treatment decisions in patients for whom timely results of ADAMTS13activity testing are unavailable. Funding The Luick Family Fund of Massachusetts General Hospital.