PB1211 - Individual determination of the components of the fibrinolytic system in platelet-depleted plasma and derived euglobulin fraction

Background: Global fibrinolytic capacity of plasma (GFC) and euglobulin clot lysis time (ECLT) exhibit distinct methodologies to facilitate clot lysis (addition of exogenous t-PA, removal of inhibitors respectively). Their sensitivity to fibrinolysis inhibitors deficiency is unclear.
Few data are available concerning redistribution of fibrinolysis inhibitors and activators in the euglobulin fraction, and correlation between GFC and ECLT and fibrinolysis inhibitors and activators levels.

Aims: i) To measure the amount of several components of the fibrinolytic system in both platelet-depleted plasma and derived euglobulin fraction,
ii) To assess their correlations with ECLT and GFC.

Methods: The study was approved by the local Ethics Committee (NUB: B0392020000042).
Fibrinolysis components were measured in citrated platelet-depleted plasma from 20 healthy volunteers and derived euglobulin fraction, according to the experimental design summarized in Figure 1.
Statistical analyses were performed in R (v4.1.2).

Results: Results are summarized in Table 1.
Large reduction in α2-antiplasmin activity, α2-macroglobulin and TAFI antigen levels in the euglobulin fraction as compared with platelet-depleted plasma (-87.7%, -100%, and -79.7% respectively). Massive reduction in PAI-1 activity level (-99.6%) despite a negligible reduction in PAI-1 antigen level (-9.2%).
Moderate to very strong correlations between ECLT and PAI-1 activity (ρ=0.865) and antigen (ρ=0.457), and α2-antiplasmin activity (ρ=0.462) levels in plasma.
Moderate to strong correlations between ECLT and t-PA antigen (ρ=0.743), and PAI-1 antigen (ρ=0.559) and activity (ρ=0.477) levels in the euglobulin fraction.
Moderate to strong correlations between GFC and t-PA antigen (ρ=0.496), α2-antiplasmin activity (ρ=0.474), and PAI-1 antigen (ρ=0.669) and activity (ρ=0.690) levels in plasma.

Conclusion(s): PAI-1 was still present in the euglobulin fraction but in an inactive conformation, shifting the PAI-1/t-PA equilibrium.
Despite their distinct methodologies, ECLT and GFC were both mainly correlated with PAI-1 (antigen and activity), t-PA (antigen), and α2-antiplasmin (activity). Their sensitivity to fibrinolysis inhibitors deficiency remains to be studied.