Heparin and low molecular weight heparin but not hirudin stimulate platelet aggregation in whole blood from acetylsalicylic acid treated healthy volunteers.
The platelet aggregatory effect of heparin was investigated with whole blood aggregometry in blood from healthy volunteers with collagen as activator. Tests were performed before and 3 hours after 0.5 g acetylsalicylic acid given perorally. Three protocols were tested. In the first experiment and before acetylsalicylic acid low doses (2.5 and 5 IU/ml) of heparin and low molecular weight heparin (LMW-heparin) did not affect aggregation while higher doses (25 and 250 IU/ml) had an antiaggregatory effect (p less than 0.0001). After acetylsalicylic acid, and with the same amount of collagen as before acetylsalicylic acid, aggregation decreased by 82 +/- 4%. Both heparin and LMW-heparin increased the aggregation (p less than 0.05). In the second experiment the collagen dose was titrated to give a similar light to moderate degree of aggregation before as compared to after acetylsalicylic acid. Low doses of heparin (p less than 0.01) but not hirudin increased the aggregation to the same degree before and after acetylsalicylic acid. In the third experiment the RGDS peptide (ARG-GLY-ASP-SER), a blocker of GPIIb/IIIa platelet receptor dose dependently inhibited platelet aggregation by 93 +/- 17%. With added RGDS peptide heparin still increased aggregation (p less than 0.001). In conclusion, with whole blood aggregometry both heparin and LMW-heparin but not the specific thrombin inhibitor hirudin stimulated platelet aggregation before and after acetylsalicylic acid ingestion. The heparin aggregatory effect was not inhibited by the RGDS peptide implying platelet activation via non specific mechanisms. These heparin effects could be of clinical importance for the treatment of arterial thromboembolic disease.
Chen
J H
JH
Department of Medicine, Huddinge University Hospital, Sweden.
Karlberg
K E
KE
Sylvén
C
C
D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D013268:Stimulation, Chemical
D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D009842:Oligopeptides; D010980:Platelet Membrane Glycoproteins; D006493:Heparin; D003094:Collagen; C046617:arginyl-glycyl-aspartyl-serine; D001241:Aspirin