A comparison of the antithrombotic and haemorrhagic effects of low molecular weight heparin fractions: the influence of the method of preparation.

Bleeding is an important complication of heparin therapy. A number of low molecular weight heparin fractions produce less bleeding than standard heparin for an equivalent antithrombotic effect in experimental animals. Low molecular weight heparin fractions and fragments are produced by a number of different procedures but their relative effects on haemostasis and thrombosis have not been evaluated. We have compared the antithrombotic and haemorrhagic effects of two low molecular weight heparin fragments and of a heparinoid with porcine mucosa heparin and related these in vivo findings to the results of ex vivo tests of blood coagulation and in vitro tests of platelet vivo tests of blood coagulation and in vitro tests of platelet function. Haemorrhage was assessed using a rabbit ear bleeding model. The antithrombotic effects were assessed by measuring inhibition of a tissue thromboplastin-induced jugular vein thrombus and by inhibition of fibrin and platelet accumulation in an arterial-venous shunt. The ex vivo anticoagulant effects were assessed with the thrombin clotting time, activated partial thromboplastin time and anti-Xa assay, and the effect of these glycosaminoglycans on platelet function was assessed by measuring collagen-induced platelet aggregation. For a similar antithrombotic effect, standard heparin produced significantly more bleeding than the other 3 glycosaminoglycans. The antithrombotic effects of all 4 glycosaminoglycans occurred at similar levels of anti-Xa activity but there was no relationship between blood loss and the effects of these glycosaminoglycans on any of the other tests of blood coagulation. Standard heparin had a greater inhibitory effect on collagen-induced platelet aggregation than the low molecular weight glycosaminoglycans, supporting the possibility that the increased bleeding observed with heparin is related in part to its inhibitory effect on platelet function.