Abstract : Objective To investigate the clinical significance of thrombomodulin (TM) and tssue plasminogen activator-plasminogen activator inhibitor-1 complex ( tPAIC) in heatstroke. Methods A retrospective analysis was conducted on 45 heatstroke patients admitted to the Intensive Care Unit of the 908th Hospital of PLA Logistic Support Force from June 2016 to September 2022. The patients were divided into 2 groups : heat exhaustion group( n=23) and heatstroke group( n=22) according to the severity of heat ilness. The results of conventional coagul ation tests, thromboelastogram ( TEG)，and coagulation markers，including TM，thrombin antithrombin complex (TAT) , plasmin-a2 anti-pl asmin inhibitor complex ( PIC) and t-PAIC within 2 hours after admission, were statistically analyzed. Results Conpared with the heat exhaustion patients, the plasma levels of TM [17.1 (9.2, 24.7) vs 7.3(5.4, 9.3 )TU/mL],TAT [23.4 (10.4, 44.3) vs 2.6( 1.5, 7.2)ng/mL], PIC [2.0 (0.9, 5.2) vs 0.7(0.4, 1.0) μg/mL] and t-PAIC [17.0 (8.3, 44.1 vs 3.8(2.1, 7.0) ng/mL] in the heat stroke patients were significantly increased ( P<0.05 ). Combining univariate and multivariate Logistic regression analysis, TM and t-PAIC were shown as the independent risk factors for heatstroke. The area under the ROC curve of TM combined with t-PAIC was 0.916 ( 95%CI:0.839 to 0.993, P<0.001). When TM>8.2 TU/mL, t-PAIC>8.7 ng/ mL, the sensitivity,specifieity, positive predictive value and negative predictive value were 95.5%，69.6%, 75.0%， and 94.1% , respectively. Conclusion The levels of TM, TAT, PIC and t-PAIC of the patients with heatstrokk may si gnificantly increase. The results of TM combined with t-PAIC should be of clinical value in the diagnosis of heatstroke.