Regular ArticleIncreased expression of platelet P-selectin and formation of platelet–leukocyte aggregates in blood from patients treated with unfractionated heparin plus eptifibatide compared with bivalirudin
Section snippets
Methods
The institutional review board approved the protocol. All patients provided written informed consent. Eligible patients included adult men and women in whom performance of PCI was clinically indicated. Patients were ineligible if they had received abciximab during the preceding week or eptifibatide or tirofiban within the past 48 h; had a contraindication to UFH, eptifibatide or bivalirudin; or were pregnant or breastfeeding. Patients with and without diabetes mellitus were randomized
Characteristics of patients studied
We studied 60 patients of whom 34 were randomized to bivalirudin and 26 to UFH + E. Their clinical characteristics are shown in Table 1. Most of the patients had stable symptoms of coronary artery disease, with cardiac catheterization performed as an elective procedure. In those with unstable angina, catheterization was performed during their admission for unstable angina. Thirty three percent had diabetes mellitus. Most procedures involved PCI of a single vessel. Two patients in the UFH + E group
Platelet–leukocyte aggregates
To determine whether the increased propensity of platelets to express P-selectin on their surfaces had functional implications, we quantified the presence of platelet–neutrophil (PNA) and platelet–monocyte (PMA) aggregates in coronary blood before and after PCI. A greater prevalence of PNA and PMA was evident in patients treated with UFH + E compared with bivalirudin (Fig. 3). Similar to the case with expression of P-selectin the greatest difference was apparent shortly after initiation of
Influence of clopidogrel
An additional analysis was performed to determine whether pretreatment with clopidogrel altered the influence of either of the two treatment regimens studied. Table 2 shows the results for platelet function, prevalence of platelet–leukocyte aggregation and the concentration of MPO with respect to pretreatment with clopidogrel. Pretreatment with clopidogrel attenuated differences in platelet function and platelet–leukocyte aggregation seen with the 2 anti-thrombotic regimens before and
Discussion
In this comparison of the effect of UFH + E compared with bivalirudin in vivo, we observed greater agonist-induced expression of P-selectin in whole blood samples obtained before PCI from patients treated with UFH + E. The functional significance of the increased platelet reactivity was suggested by an increased prevalence in vivo of platelet–leukocyte aggregates and evidence of greater activation of leukocytes in those treated with UFH + E compared with bivalirudin. We obtained blood from the
Acknowledgements
The authors thank Mary Lord, RN, for her expert assistance. The study was supported by a grant from The Medicine Company.
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