Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor

• Published in: Circulation (New York, N.Y.) N.Y.), 1998-01, Vol.97 (3), p.251-256
• Main Authors: XIAO, Z, THEROUX, P
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - pharmacology; Adult; Aged; Aged, 80 and over; Angina, Unstable - blood; Angina, Unstable - drug therapy; Anticoagulants - administration & dosage; Anticoagulants - therapeutic use; Antithrombins - administration & dosage; Antithrombins - therapeutic use; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Dose-Response Relationship, Drug; Enoxaparin - administration & dosage; Enoxaparin - therapeutic use; Female; Heparin - administration & dosage; Heparin - therapeutic use; Humans; Male; Medical sciences; Middle Aged; P-Selectin - blood; P-Selectin - drug effects; Partial Thromboplastin Time; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; Pipecolic Acids - administration & dosage; Pipecolic Acids - therapeutic use; Platelet Activation - drug effects; Platelet Count; Platelet Glycoprotein GPIIb-IIIa Complex - drug effects; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.97.3.251

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. 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