Effects on platelets and on the clotting system of four glycosaminoglycans extracted from hog mucosa and one extracted from aortic intima of the calf.
A commercial heparin preparation, a heparin fraction with a molecular weight of 12,000 Daltons, heparan sulfate, dermatan sulfate obtained from hog mucosa, and mesoglycan, an heparinoid obtained from calf aortic intima were investigated. Commercial mucous heparin had a stimulatory effect on platelet aggregation induced by ADP, while the others failed to do so. Dermatan sulfate had a dose dependent inhibition and commercial mucosal heparin, a dose dependent stimulation, on serotonin release induced by ADP. Both the commercial mucosal heparin and dermatan sulfate showed an inhibition and the other glycosaminoglycans (GAGs) a negligible effect on collagen induced platelet aggregation. The collagen induced serotonin release was clearly reduced by all GAGs; heparan sulfate had this activity only at the highest doses used. Commercial mucosal heparin produced the highest activity on clotting systems as measured by activated partial thromboplastin time, while mesoglycan had the strongest anti-factor Xa specific activity as measured by a clotting assay. Dermatan sulfate was the weakest on both assays. When we injected intravenously an equivalent amount (about 60 mg) of heparin fraction, heparan sulfate, dermatan sulfate and mesoglycan in three different volunteers with an interval of 20 days after each injection, we had an immediate platelet factor 4 (PF4) release only with heparin fraction, heparan sulfate and mesoglycan. Heparin fraction and mesoglycan, in spite of having a wide discrepancy in anticoagulant effect, caused almost the same PF4 release. GAGs which can neutralize PF4 and which can also have specific anti-factor Xa activity could represent a great advantage in thrombosis prophylaxis.
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects*; D002417:Cattle; D003871:Dermatan Sulfate / Q000494:pharmacology; D005170:Factor X / Q000037:antagonists & inhibitors; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000494:pharmacology; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000032:analysis; D012701:Serotonin / Q000378:metabolism; D013552:Swine
D003871:Dermatan Sulfate; D005170:Factor X; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D010978:Platelet Factor 4; D012701:Serotonin; C040617:mesoglycan