Platelet aggregation, sensitivity to prostaglandin E1 and thromboxane A2 release in recombinant hirudin- and heparin-anticoagulated blood.
Hirudin is the most potent known natural inhibitor of thrombin and is presently gaining popularity as an anticoagulant since recombinant forms have become available. The aim of the present study was to compare platelet aggregation, sensitivity to prostaglandin E1 and thromboxane A2 release in r-hirudinized and heparinized blood. Platelet aggregation was measured turbidimetrically using a dual channel aggregometer (Labor, Germany) in blood samples of healthy volunteers anticoagulated with r-hirudin W015 (Behring) and heparin (20 micrograms/ml blood each). Aggregation was induced by arachidonic acid (0.5, 1.0 and 2.0 mM) and adenosine diphosphate (1.0 microM). Prostaglandin E1 in concentrations 10, 20, 40 and 80 ng/ml was used. Plasma thromboxane B2 content was measured by gas chromatography/mass spectrometry. This study showed a significantly lower arachidonic acid induced platelet aggregation in r-hirudinized plasma. Three minutes after the aggregation induction by 0.5 mM arachidonic acid the plasma thromboxane B2 concentration was 23.0 ng/ml in blood anticoagulated with r-hirudin and 108.4 ng/ml in heparin-anticoagulated blood. The extent of the aggregation induced by adenosine diphosphate was nearly the same in hirudinized and heparinized plasma. Platelet sensitivity to prostaglandin E1 was significantly higher in r-hirudinized blood. Thus, platelet aggregation induced by arachidonic acid is significantly lower and sensitivity to prostaglandin E1 higher in r-hirudin-anticoagulated blood in comparison with heparin-anticoagulated blood.
Viigimaa
M
M
Department of Cardiology, Tartu University Hospital, Estonia.
Tsikas
D
D
Frölich
J C
JC
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000527:Alprostadil / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006493:Heparin / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism*
D006629:Hirudins; D011994:Recombinant Proteins; D016718:Arachidonic Acid; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D006493:Heparin; D000527:Alprostadil