Plasma PF4 is a reliable biomarker of platelet reactivity and predictive of bleeding risk in DAPT patients undergoing cardiac surgery.

Abstract

Background: Platelet activation is crucial for hemostasis and thrombosis, particularly in patients on antiplatelet therapy. Managing bleeding risk during cardiac surgery requires understanding platelet dynamics, especially when antiplatelet agents are maintained until the coronary artery bypass surgery (CABG).

Aims: to explore the relevance of plasma levels of sCD40L, sP-Selectin, PF4, and NAP-2 in predicting bleeding events during CABG in patients under dual antiplatelet therapy (clopidogrel+aspirin, DAPT) or aspirin.

Methods: Platelet reactivity before CABG was assessed in 143 patients by plasma levels of sCD40L, sP-Selectin, PF4, and NAP-2 as well as platelet aggregation tests and platelet membrane expression of P-Selectin. Postoperative bleeding was monitored at 24 h with the chest tube blood output.

Results: Patients receiving DAPT demonstrated markedly reduced plasma levels of PF4 and NAP-2 compared to patients on aspirin alone (PF4: 676 vs. 992 ng/ml, p < 0.001; NAP-2: 167 vs. 281 ng/ml, p < 0.001). PF4 and NAP-2 levels correlated with 10 and 20 µM ADP-induced and collagen-induced platelet aggregation (p = 0.01) but not with arachidonic acid or PAR1ap as agonists. Platelet membrane P-Selectin expression before CABG was significantly correlated with PF4 and NAP-2 levels (r = 0.26, p < 0.001 for PF4, r = 0.23, p = 0.01 for NAP-2), confirming its role in reflecting basal platelet activation. sP-Selectin and sCD40L showed no significant correlation with any clinical outcomes, treatment group or platelet activation test whereas PF4 and NAP-2 were independently correlated with increased 24-hour bleeding volume (PF4: r =-0.19 p = 0.03; NAP-2: r=-0.17 p = 0.04).

Conclusion: PF4 is the most platelet-specific biomarker for predicting platelet reactivity and bleeding in patients receiving DAPT until the CABG. Plasma PF4 quantification could provide a simpler alternative to aggregation tests for predicting platelet reactivity, postoperative bleeding and could guide perioperative antiplatelet management.