The Lack Of Relationship Between Anti-Xa Activity And Antithrombotic Activity Of Low Molecular Weight Heparin

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.