Thrombin generation and all-cause mortality in The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Abstract

Introduction: Thrombin generation assay (TGA) is a laboratory method that provides the global evaluation of hemostasis. The association between thrombin generation and all-cause mortality is poorly investigated and results are contradictory. This study evaluated whether TGA parameters are associated with all-cause mortality in a prospective cohort.

Methods: This study was conducted in 2,588 participants enrolled at baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). TGA was performed using the Calibrated Automated Thrombogram (CAT) method, and its parameters lagtime, time-to-peak, peak, Endogenous Thrombin Potential (ETP) and normalized ETP (nETP) were evaluated according to the reference interval (RI). The association between TGA parameters and all-cause mortality was estimated by Cox regression and adjusted for confounders.

Results: The mean follow-up time was 6.6 ± 2.7 years and 85 deaths occurred. After adjustment, time-to-peak values above the RI at low and high tissue factor (TF) concentrations were associated with higher risk of death [HR = 2.45 (95 % CI: 1.17-5.13) and HR = 2.24 (95 % CI: 1.02-4.93), respectively] and nETP and peak values below RI at high TF concentration were associated with higher risk of death [HR = 3.85 (95 % CI: 1.39-10.68) and HR = 2.56 (95 % CI: 1.17-5.61), respectively].

Conclusions: Delayed thrombin generation was associated with higher risk of all-cause mortality.

Keywords: Adult; All-cause mortality; Blood Coagulation Tests; Calibrated automated thrombogram; Cohort Studies; Thrombin generation.