THE RELATIVE IMPORTANCE OF THROMBIN INHIBITION AND FACTOR-XA INHIBITION TO THE ANTITHROMBOTIC EFFECTS OF HEPARIN

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 65  (1) , 198-201
Abstract
The relative importance of antithrombin and anti-factor Xa activities of heparin fractions required to achieve optimal antithrombotic effects is unknown. The effects of standard heparin, an octasaccharide heparin fraction (anti-factor Xa activity only), and dermatan sulfate (antithrombin activity only) on the prevention of thrombosis were examined and this was related to their anticoagulant effects in vivo in rabbits. Thrombosis was measured as the incorporation of 125I-fibrinogen into tissue thromboplastin-induced thrombi using a Wessler-type model. Ex vivo changes in thrombin clotting time (TCT) were used as an index of antithrombin activity, and a chromogenic anti-factor Xa assay was used to measure anti-factor Xa activity. In addition, the ability of the 3 sulfated polysaccharides to simultaneously inhibit the generation of thrombin activity and to enhance the inactivation of the factor Xa added to initiate thrombin generation in plasma was determined. Standard heparin, in a dose of 10 anti-factor Xa U/kg, inhibited thrombus formation by 90%, prolonged the TCT by 2 s, and resulted in an anti-factor Xa level of 0.32 U/ml. The octasaccharide heparin fraction, in a dose of 10 anti-factor Xa U/kg, inhibited thrombus formation by 41%, had no effect on the TCT, and resulted in an anti-factor Xa level of 0.28 U/ml. Higher doses of the octasaccharide resulted in a further increase in the anti-factor Xa levels but had no further effect on thrombus formation. Dermation sulfate, in a dose of 500 .mu.g/kg, inhibited thrombus formation by 95%, but had no effect on the TCT. The antithrombotic effect achieved by inhibiting factor Xa apparently is limited and better antithrombotic effects are achieved by heparin or heparin-like substances capable of influencing the inactivation and/or the generation of thrombin.