Effect of heparin and heparinoids on platelet aggregation.
Biological effectiveness of bovine lung heparin and porcine mucosal heparin was tested in vitro and compared with the effectiveness of 12 semisynthetic heparinoids obtained by sulfation of waste heparin mucopolysaccharides and other biomolecules. Equieffective concentrations of these substances were determined in the sense of prolongation of the thrombin time and the APTT, inhibition of the thrombin- and collagen-induced aggregation, and potentiation of the primary ADP-induced aggregation. The influence of sulfation was proved on the biological effectiveness as well as the significance of the proper choice of the parent structure. Some polycondensates of the polysaccharide type were effective altogether with the sulfated waste heparin mucopolysaccharides. On the contrary, protein structures and low molecular weight glycosides exhibited little or no activity. The effective substances were related to heparin not only by the anticoagulant activity but also by the inhibitory action on the thrombin- and collagen-induced platelet aggregation. Contrary to heparin, higher concentrations of the studied heparinoids strongly potentiated the ADP-induced aggregation response. Strong inhibition of the collagen-induced aggregation was proved after administration of heparin to patients with end-stage renal failure on days without haemodialysis. Less significant changes in the secondary aggregation were observed also after administration of S-heparin (one of the studied heparinoids) to volunteers in the form of the rectal suppositories.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000494:pharmacology*; D006496:Heparinoids / Q000494:pharmacology*; D006801:Humans; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000494:pharmacology; D013918:Thrombin Time
D006496:Heparinoids; D000244:Adenosine Diphosphate; D006493:Heparin; D003094:Collagen; D013917:Thrombin