The effectiveness of low dose heparin in the prevention of venous thrombosis and pulmonary embolism has been attributed to its enhancement of plasma anti-Xa activity. Low molecular weight (MW) heparin fractions have a relatively high anti-Xa activity, both in vitro and ex vivo, and it has been assumed that this high anti-Xa activity correlates with antithrombotic activity.
We have compared the antithrombotic effect of a very low MW heparin fraction (mean MW 3,000) with standard heparin (mean MW 15,000) using a rabbit prophylaxis model and thromboplastin as the thrombogenic stimulus. The antithrombotic effect of these heparins was related to ex vivo anti-Xa heparin activity. Both heparins showed a dose-dependent antithrombotic effect, enabling the relative antithrombotic and anti-Xa activities to be compared over a dosage range. Even when the ex vivo anti-Xa activity achieved with the low MW heparin was significantly greater than for the standard heparin (0.41 and 0.16 anti-Xa units per ml; p < 0.01), significantly less inhibition of thrombosis was observed with the low MW heparin fraction (24% and 88%; p < 0.02). For an equivalent antithrombotic effect (50% inhibition of thrombosis) an ex vivo anti-Xa activity in excess of five fold was required in the low MW heparin treated animals. These findings are in contrast with our previous experience using a low MW fraction (mean MW 4,600) and suggest that the relationship between anti-Xa activity and antithrombotic effect may be MW dependent.