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(Circulation. 1998;97:251-256.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

Platelet Activation With Unfractionated Heparin at Therapeutic Concentrations and Comparisons With a Low-Molecular-Weight Heparin and With a Direct Thrombin Inhibitor

Zihui Xiao, MSc; ; Pierre Théroux, MD

From the Department of Medicine, Montreal Heart Institute and University of Montreal, Montreal, Canada.

Correspondence to Dr Pierre Théroux, Montreal Heart Institute, 5000 Bélanger St E, Montreal, Quebec H1T 1C8, Canada.

Background—The growing use of heparin in acute thrombotic disorders, coupled with the availability of many new antithrombotic agents, emphasizes the need for adequate characterization of the platelet effects of the various anticoagulants. Controversial platelet effects have been reported with heparin (eg, enhanced platelet activation in vitro with high doses and no such effect in vivo at therapeutic doses). This study examined platelet receptor activation and platelet aggregation at therapeutic concentrations of unfractionated heparin (UFH), of enoxaparin, a low-molecular-weight heparin, and of argatroban, a direct thrombin inhibitor.

Methods and Results—Platelet P-selectin (CD62) and activated GP IIb/IIIa (PAC-1) expression on platelet membrane was quantified in whole blood as well as platelet aggregation in platelet-rich plasma in 43 patients with unstable angina before and during treatment with UFH or enoxaparin. Studies were also carried out in blood of seven normal volunteers after addition ex vivo of UFH (0.25 U/mL), enoxaparin (0.25 U/mL), argatroban (1 ng/mL), and normal saline. UFH in patients with unstable angina increased the percentage of circulating platelets positive to PAC-1 from 2.7±1.7% to 4.4±3.4% (P<.05) and to CD62 from 1.6±0.9% to 2.7±1.5% (P<.01). Platelets were also hyperresponsive to stimulation with ADP and with the thrombin-receptor agonist peptide. Aggregation to ADP increased from 6.8±4.6% to 11.2±7.0% and to TRAP from 5.2±3.5% to 11.1±6.0% (P<.001). The addition of UFH to blood of normal volunteers resulted also in activation of GP IIb/IIIa receptors, expression of P-selectin, and enhanced platelet aggregation. Enoxaparin had only minor effects on platelet activation in vivo and ex vivo, and argatroban, evaluated ex vivo, had no detectable effects.

Conclusions—Therapeutic concentrations of UFH are associated with platelet activation.

Key Words: platelets • cell adhesion molecules • glycoproteins • heparin

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