Decreased platelet reactivity in blood anticoagulated with bivalirudin or enoxaparin compared with unfractionated heparin: implications for coronary intervention.
BACKGROUND
Platelet reactivity predicts complications after percutaneous coronary intervention (PCI). Accordingly, agents that suppress platelet reactivity should decrease adverse events after PCI. This study was designed to determine the effects of therapeutic concentrations of unfractionated heparin (UFH), bivalirudin, or enoxaparin alone or in combination with tirofiban on platelet reactivity.


METHODS
Blood taken from 13 patients with coronary artery disease was exposed to each anticoagulant alone or in combination with tirofiban ex vivo. Platelet reactivity was characterized with flow cytometry to quantify the percentage of platelets capable of binding fibrinogen (activation of glycoprotein IIb-IIIa) and expressing P-selectin in response to adenosine diphosphate (ADP, 0, 0.2, and 1 microM).


RESULTS
Platelet reactivity was greater in blood treated with UFH than in blood anticoagulated with bivalirudin with respect to both the capacity to bind fibrinogen (by 4 +/- 1.8%, p = 0.01) and P-selectin expression (by 7.7 +/- 0.7%, p, < 0.0001) in response to 1 microM ADP. Platelet reactivity was greater in blood treated with UFH than in blood exposed to enoxaparin with respect to P-selectin expression (by 7 +/- 1.1%, p, < 0.0001) in response to 1 microM ADP. Platelet reactivity was similar in blood treated with bivalirudin or enoxaparin. Addition of tirofiban suppressed the capacity to bind fibrinogen in the presence of each anticoagulant to a similar extent.


CONCLUSIONS
As platelet reactivity is greater in blood anticoagulated with UFH in comparison with blood anticoagulated with enoxaparin or bivalirudin, the use of bivalirudin or enoxaparin rather than UFH during PCI should contribute to a reduced incidence of adverse cardiac events after PCI.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D004341:Drug Evaluation; D017984:Enoxaparin / Q000494:pharmacology; D005434:Flow Cytometry; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D019007:P-Selectin / Q000032:analysis; D010446:Peptide Fragments / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D000925:Anticoagulants; D017984:Enoxaparin; D006629:Hirudins; D019007:P-Selectin; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D000244:Adenosine Diphosphate; D006493:Heparin; C074619:bivalirudin