Background: Besides its anticoagulant effects, heparin is known to alter platelet (PLT) function. We examined the effects of unfractionated heparin on PLT function in patients with stable coronary artery disease (CAD).
Methods and Results: PLT function was evaluated by whole-blood flow cytometry to detect PLT CD62 expression and by impedance aggregometry to assess platelet aggregation (PA) before and after bolus intravenous administration of low-dose heparin (2713 ± 1231 U) in 16 patients undergoing coronary angiography (group 1) and high-dose heparin (7937 ± 2414 U) in 16 patients undergoing coronary angioplasty (group 2). Activated clotting time (ACT) and plasma antifactor-Xa heparin levels also were measured. Heparin increased PLT CD62 expression, which was significantly more pronounced in group 1 patients with plasma heparin levels less than 0.7 U/mL and ACT of 222 ± 52 seconds compared with group 2 patients with heparin levels greater than 0.7 U/mL and ACT of 365 ± 86 seconds (8 ± 9 v -1 ± 4% change in resting PLTs, P = .01, and 11 ± 12 v 1 ± 6% increase in adenosine diphosphate (ADP) [5 μM]-stimulated PLTs, P = .02). Heparin produced a slight increase in PA in group 1 patients (1.4 ± 5.3 ohms) as compared with the group 2 patients, where it significantly suppressed PA (-3.0 ± 5.3 ohms, P < .05 v group 1). A strong and statistically significant negative correlation between change in platelet CD62 expression and heparin concentration was observed in group 1 patients (r = -.5, P = .05, —ADP; r = —.65, P = .006, +ADP), whereas this relationship was weak and did not reach statistical significance in group 2 patients (r = -0.4, P = .2, -ADP; r = .11, P = 0.9; +ADP).
Conclusion: Bolus administration of intravenous heparin augmented PLT activation in patients at clinically relevant anticoagulant concentrations (<0.7 U/mL). These findings may have implications for optimal dosing strategy for heparin as an antithrombotic agent in clinical situations characterized by platelet-dependent thrombotic events.
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