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Thrombin regulation of platelet interaction with damaged vessel wall and
isolated collagen type I at arterial flow conditions in a porcine model:
effects of hirudins, heparin, and calcium chelation
L Badimon, JJ Badimon, R Lassila, M Heras, JH Chesebro and V Fuster
Division of Cardiology, Mount Sinai School of Medicine, New York, NY.
The role of thrombin inhibition in platelet vessel wall interaction and
thrombus growth was studied under controlled flow conditions. Natural
hirudin and recombinant hirudin (r-hirudin), which are specific thrombin
inhibitors, were compared with heparinized blood (1.8 +/- 0.2 U/mL) and
Ca(2+)-chelated blood in their potential to inhibit platelet interaction
and thrombus growth on two biologic vascular surfaces and one immobilized
vessel wall component. The substrates were perfused by flowing blood at
shear rates typical of patent and stenosed arteries (212 to 1,690/s) for 5
minutes. Platelet deposition was measured by In- 111-labeled platelets. We
found that both natural and r-hirudin have similar effects on
platelet-substrate interaction. As compared with heparin, platelet
deposition to mildly damaged vessel wall and digested collagen type I was
not reduced by hirudin or citrate. However, hirudin and citrate
significantly reduced platelet deposition to severely damaged vessel wall
(platelets x 10(6)/cm2: 93 +/- 10 in heparinized blood v 50 +/- 7 in blood
treated with 100 U/mL r-hirudin). Therefore, thrombus growth on areas of
severe wall damage is in part dependent on local thrombin production at the
site of vascular damage. We also found that hirudin added to heparinized
blood reduced platelet deposition to severely injured wall but not to
subendothelium or collagen-coated slides. Hirudin added to citrated blood
did not affect platelet deposition. Our study indicates that local thrombin
generation at the site of severe injury will induce platelet activation and
deposition even in the presence of average therapeutic heparin levels that
inhibit blood coagulation.
Volume 78,
Issue 2,
pp. 423-434,
07/15/1991
Copyright © 1991 by The American Society of Hematology
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