Determinants of plasma fibrin clot lysis measured using three different assays in healthy subjects

Several methods for measuring fibrinolytic capacity in plasma have been developed yielding frequently inconsistent results. We investigated which factors determine fibrinolytic capacity in three plasma-based assays.

In 80 apparently healthy controls (aged 43 ± 10 years, 50 women [62.5%]) we evaluated fibrinolysis using three assays: (1) by Pieters et al. (CLT2018), (2) by Lisman et al. (CLT), and (3) by Carter et al. (Lys50). Coagulation factors and fibrinolytic proteins, including histidine-rich glycoprotein (HRG) and γ'-fibrinogen, were determined. Regression models were performed to identify determinants of lysis times.

Positive correlations were observed between CLT2018 and both CLT (r = 0.73) and Lys50 (r = 0.61), as well as between CLT and Lys50 (r = 0.46, all p < 0.001). The main determinants of both CLT2018 and CLT were plasminogen activator inhibitor-1 (PAI-1), followed by thrombin-activatable fibrinolysis inhibitor (TAFI) and α₂-antiplasmin. Histidine-rich glycoprotein was a predictor of the longest-normal CLT2018 alone (OR 1.04, 95% CI 1.02-1.06). α₂-Antiplasmin and fibrinogen levels, followed by PAI-1 and TAFI determined Lys50. After adjustment for age, sex, and body mass index, C-reactive protein (CRP) was an independent predictor of the top quartiles of the three lysis times.

We showed that apart from PAI-1, TAFI, and α₂-antiplasmin, several other factors, in particular CRP, can affect the results of global fibrinolysis tests used in research. Our findings may help understand why the choice of a specific fibrinolysis assay can affect the presence and/or magnitude of intergroup differences in fibrinolytic capacity in a given disease state.