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Thrombosis |
From the Divisions of Angiology (S.S., D.S., E.M., C.W.K.) and Cardiology (K.H., C.K.), 2nd Department of Medicine, University of Vienna, Austria.
Correspondence to Christoph W. Kopp, MD, 2nd Department of Medicine, Division of Angiology, University of Vienna, General Hospital Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. E-mail christoph.kopp{at}univie.ac.at
Objective Activated platelets rapidly adhere to monocytes and upregulate the expression of tissue factor (TF), the major trigger of the coagulation cascade. In this study, we examined the effect of abciximab, a nonselective glycoprotein IIb/IIIa-receptor antagonist, on monocyte TF expression in thrombin receptor activatorstimulated whole blood in vitro.
Methods and Results Abciximab (50 µg/mL) reduced the mass of platelets attached to monocytes, measured by the mean fluorescence intensity (MFI) of CD42b on CD14+ cells, 1 (CD42b, 471±197 versus 1073±217 MFI, mean±SD, P<0.05), 5, and 10 minutes after thrombin receptor activator stimulation of whole blood to the same extent as antiP-selectin (50 µg/mL; 288±177 MFI, P<0.05) when determined by flow cytometry. In parallel, the expression of the platelet activation marker P-selectin colocalized with CD14+ monocytes was reduced up to 25% by abciximab at the same time points. Expression of monocyte TF antigen (CD14+/TF+, 39.9±8.7% versus 66.3±19.9%, P<0.05), chromogenic TF-activity (TF, 8.4±1.9 versus 13.2±2.8 U, arbitrary units, P<0.05), and TF mRNA was suppressed in the presence of abciximab as a consequence of reduced platelet mass attached to monocytes.
Conclusions Our data suggest that heterotypic monocyte-platelet aggregates are a target for abciximab, which suppresses monocyte TF because of a reduction of monocyte-platelet cross talk.
Key Words: tissue factor glycoprotein IIb/IIIa inhibition abciximab monocyte-platelet aggregates flow cytometry
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