ISTH definition of pulmonary embolism-related death and classification of the cause of death in venous thromboembolism studies: Validation in an autopsy cohort

Background: The International Society on Thrombosis and Haemostasis (ISTH)’s Scientific and Standardization Committee (SSC) recently proposed a definition of pulmonary embolism (PE)-related death. Objectives: To evaluate the accuracy and interrater reliability of the ISTH definition of PE-related death in an autopsy cohort. Methods: We reviewed reports of 1064 consecutive adult autopsies that were performed at the NewYork-Presbyterian Hospital from January 2010 until July 2019. We included all patients with autopsy-confirmed PE-related death (cases) during that time frame, combined with patients who died in 2018 from a cause other than PE (controls). Based on clinical summaries, two adjudicators independently adjudicated the cause of death in each patient using the ISTH classification for the cause of death, blinded to the case/control status and ratio. The primary outcome was autopsy-confirmed PE-related death. We determined the sensitivity and specificity of the ISTH definition to identify autopsy-confirmed PE-related death, and its interrater reliability using the percentage agreement and Cohen's kappa. Results: A total of 126 patients who underwent autopsy were included in the analysis (median age, 68 years [range, 21–94], 60 [48%] women), of which 29 (23%) had died from PE as confirmed by autopsy. The ISTH definition's sensitivity and specificity for autopsy-confirmed PE-related death were 45% (95% CI, 26–64) and 99% (95% CI, 94–100), respectively. Interrater reliability for PE-related death was substantial (percentage agreement, 94% [95% CI, 89–97]; kappa, 0.73 [95% CI, 0.55–0.97]). Conclusion: Adjudication of the cause of death using the ISTH definition resulted in very high specificity, moderate sensitivity, and good interrater reliability for PE-related death.