Leukocyte-platelet aggregation, platelet surface P-selectin, and platelet surface glycoprotein IIIa after percutaneous coronary intervention: Effectsof dalteparin or unfractionated heparin in combination with abciximab

Background Plaque disruption with resultant platelet activation and leukocy te-platelet aggregation is a pathophysiologic process common to both acute coronary syndromes and percutaneous coronary interventions. Unfractionated heparin is a standard antithrombotic therapy in patients with both acute co ronary syndromes and in those undergoing percutaneous coronary intervention s. Low-molecular-weight heparins have been reported to cause less platelet activation than unfractionated heparin. Methods Monocyte-platelet aggregates, neutrophil-platelet aggregates, plate let surface P-selectin, and platelet surface glycoprotein (GP) IIIa were me asured serially by whole blood flow cytometry in 40 patients with unstable angina (randomly assigned to either unfractionated heparin 70 U/kg or the l ow-molecular-weight heparin dalteparin 60 IU/kg) undergoing coronary interv ention with planned abciximab administration (in 2, one-half-dose boluses). Assays were performed at baseline, 5 minutes after administration of eithe r type of heparin, 10 minutes after the first bolus of abciximab, 10 minute s after second bolus of abciximab, and 8 to 10 and 16 to 24 hours after adm inistration of either heparin. Results No significant differences in clinical outcomes were observed betwe en patients receiving either unfractionated heparin or dalteparin. The numb er of circulating P-selectin-positive platelets was increased by unfraction ated heparin but not dalteparin, and abciximab reversed this increase. The number of circulating P-selectin-positive platelets was reduced below basel ine levels in both treatment groups 8 to 10 and 16 to 24 hours after study drug administration. At 8 to 10 and 16 to 24 hours after administration of study drug, platelet degranulation in response to iso-thrombin receptor ago nist peptide 1.5 mu mol/L was significantly reduced by almost 50% (compared with immediately after study drug administration). Both unfractionated hep arin and dalteparin significantly increased the numbers of circulating mono cyte-platelet and neutrophil-platelet aggregates, which were subsequently r educed to baseline levels after administration of the second abciximab bolu s and to below baseline at both 8 to 10 and 16 to 24 hours in all patients. After both unfractionated heparin and dalteparin administration, platelet surface GP IIIa expression was significantly increased compared with baseli ne at both 8 to 10 and 16 to 24 hours. Conclusions Dalteparin in combination with abciximab in patients with unsta ble angina undergoing coronary intervention appears to be safe. Unfractiona ted heparin, but not dalteparin, degranulates platelets in patients with un stable angina. Both heparins increase the number of circulating monocyte-pl atelet and neutrophil-platelet aggregates. Abciximab therapy during coronar y interventions rapidly reduces the number of degranulated platelets and le ukocyte-platelet aggregates.