TITLE

Promotion of proinflammatory interactions between platelets and monocytes by unfractionated heparin

AUTHOR(S)
Harding, S. A.; Din, J. N.; Sarma, J.; Josephs, D. H.; Fox, K. A. A.; Newby, D. E.
PUB. DATE
November 2006
SOURCE
Heart;Nov2006, Vol. 92 Issue 11, p1635
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Objectives: To determine the in vitro effects of unfractionated heparin, fractionated heparin and direct thrombin inhibition on platelet-monocyte aggregation, and to establish the in vivo effects of unfractionated heparin and direct thrombin inhibition on platelet-monocyte aggregates in patients scheduled for percutaneous coronary intervention (PCI). Design: Platelet-monocyte aggregates were assessed in whole blood from 18 healthy volunteers after the addition of unfractionated heparin (1 U/mI), enoxaparin (0.8 U/mI) or lepirudin (5.6 g/ml), and in 28 patients scheduled for elective PCI before and after administration of 100 U/kg of unfractionated heparin or 0.75 mg/kg bivalirudin. The influence of P-selectin-mediated platelet-monocyte aggregation was assessed with specific blocking antibodies. Results: Addition of unfractionated heparin in vitro was associated with a higher level of platelet-monocyte aggregates than in controls (20.1 (1.9)% v 16.2 (1.6)%, respectively, p < 0.001). However, platelet-monocyte aggregation was not affected by enoxaparin or lepirudin (16.9 (2.0)% and 17.0 (2.2)%, respectively, NS). Intravenous unfractionated heparin in vivo also resulted in an increase in platelet-monocyte aggregates (absolute Δ 7.1 (2.7)%, p < 0.01), whereas intravenous bivalirudin had no effect (absolute Δ -1.5 (2.4)%, NS). The addition of P-selectin blockade abolished any increase in platelet-monocyte aggregates associated with heparin. Conclusions: In vitro and in vivo unfractionated heparin is associated with increased platelet-monocyte aggregation through a P-selectin-dependent mechanism. These findings provide a potential explanation for the superior cardiovascular outcomes associated with fractionated heparins and direct thrombin inhibitors.
ACCESSION #
22982755

 

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