Effects of dermatan sulfate and heparin on inhibition of thrombus growth in vivo.
The effects of dermatan sulfate and heparin on inhibition of fibrin accretion onto existing thrombi as related to their ex vivo anticoagulant activity and abilities to inhibit increased prothrombin clearance induced by thrombi were investigated. Our results indicate that for equivalent anti-thrombin activities, dermatan sulfate is a more effective inhibitor of fibrin accretion onto existing thrombi than is heparin. These observations raise the possibility that in some clinical conditions dermatan sulfate, rather than heparin, may be a better antithrombotic agent of choice. This beneficial effect of dermatan sulfate appears to be unrelated to anti-factor Xa activity either endogenous to dermatan sulfate itself (which is unlikely since it does not catalyze factor Xa inhibition) or to anti-factor Xa activity associated with other glycosaminoglycans released into the circulation following dermatan sulfate administration since this activity is less than that associated with heparin treatment. It is more likely that dermatan sulfate mediates this beneficial effect by more effectively inhibiting thrombin within a thrombus than can heparin. This possibility is supported by the ability of dermatan sulfate to normalize prothrombin consumption in animals with existing thrombi.
Van Ryn-McKenna
J
J
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Ofosu
F A
FA
Gray
E
E
Hirsh
J
J
Buchanan
M R
MR
D000818:Animals; D002807:Chondroitin / Q000031:analogs & derivatives*; D003871:Dermatan Sulfate / Q000494:pharmacology / Q000627:therapeutic use*; D015951:Factor Xa; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D011516:Prothrombin / Q000378:metabolism; D011817:Rabbits; D015842:Serine Proteinase Inhibitors; D013917:Thrombin / Q000037:antagonists & inhibitors; D013924:Thrombophlebitis / Q000097:blood / Q000188:drug therapy*
D015842:Serine Proteinase Inhibitors; D003871:Dermatan Sulfate; D011516:Prothrombin; D005337:Fibrin; D006493:Heparin; D002807:Chondroitin; D013917:Thrombin; D015951:Factor Xa