Activated partial thromboplastin time predicts mortality in patients with severe fever with thrombocytopenia syndrome: A multicenter study in North China

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high lethality. This study aimed to determine whether prolonged activated partial thromboplastin time (APTT) predicted SFTS mortality. Methods SFTS patients were enrolled from 6 hospitals in the north China. Subjects were divided into training cohort and 5 externally validation cohorts. The least absolute shrinkage and selection operator Cox regression model was performed to screen potential prognostic factors. Risk factors were analysed using multivariable regression models. Prognostic models were established by Cox regression and random survival forest (RSF) methods, and evaluated regarding discrimination, validity and clinical benefit. Time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive effectiveness of variables. Results 1332 SFTS cases were included, in which 211 patients died. Six potential prognostic factors were screened, and pulse, breath, APTT and aspartic transaminase (AST) were independently associated with mortality in both training cohort (Yantai, N=791) and external validation cohort (N=541). APTT was steadily correlated with the fatality (HR: 1.039∼1.144; all P<0.01) in each five sub-validation cohorts (Dandong, Dalian, Tai’an, Qingdao and Beijing). RSF model with variables of APTT, AST, pulse and breath had considerable prognostic effectiveness, which APTT showed the highest prognostic ability with the area under the curve of 0.848 and 0.787 for 7-day and 14-day survival, respectively. Survival differences were found between high and low levels of APTT for mortality using 50s as the optimal cut-off. Conclusions SFTS patients have prolonged APTT, which is an independent risk factor for fatality. APTT≥50s was recommended as a biomarker to remind physicians to monitor and treat patients more aggressively to improve clinical prognosis.