The importance of thrombin inhibition for the expression of the anticoagulant activities of heparin, dermatan sulphate, low molecular weight heparin and pentosan polysulphate

Abstract

The effects of standard heparin, 3 low MW derivatives of heparin, dermatan sulfate and pentosan polysulfate on the intrinsic coagulation pathway were compared to evaluate the contributions of the anti-factor Xa and anti-thrombin activities to their anticoagulant activities. The anticoagulant potency was measured by the ability of each sulfated polysaccharide to inhibit the generation of thrombin activity in plasma. Similarly, the ability of the 6 sulfated polysaccharides to enhance the rates of inactivation either factor Xa or thrombin in defibrinated plasma containing CaCl and cephalin were also determined. Standard heparin was the only sulfated polysaccharide that could equally inhibit thrombin generation and enhance the inactivation of factor Xa and thrombin by plasma. Dermatan sulfate and pentosan polysulfate were more effective as inhibitors of thrombin generation than potentiators of factor Xa inactivation. Th 2 smallest derivatives of heparin, which had high anti-factor Xa (but low antithrombin) activity, were the poorest inhibitors of thrombin generation. Only sulfated polysaccharides that enhance the inactivation of thrombin by plasma and/or inhibit the generation of thrombin activity in plasma are good anticoagulants. These 2 activities of sulfated polysaccharides appear to be good predictors of the relative antithrombotic potency in vivo.