Clexane® exerts its anticoagulant effects through potentiation of the activity of antithrombin. Although first characterised as an inhibitor of thrombin (FIIa), antithrombin also affects other coagulation factors including FXIa, FIXa, and FXa. Importantly, antithrombin also reduces FVII activity by accelerating the dissociation of the FVIIa-tissue factor complex that initiates coagulation and prevents its re-association [42].
Clexane® joins with antithrombin to form a complex. This complex undergoes a conformational change; in its altered conformation, the complex inhibits coagulation factors. The ability to inhibit FXa prevents the formation of the FXa/FVa prothrombinase complex. Owing to the higher proportion of low-molecular-weight fractions, enoxaparin displays a markedly lower anti-FIIa activity than UFH, and therefore has a higher ratio of anti-Xa to anti-IIa activity in comparison with UFH, which displays a ratio of 1:1 [38].
In addition to AT-mediated anticoagulation, there are other mechanisms that contribute to the anti-coagulation activity of Clexane®. They include the release of tissue factor pathway inhibitors (TFPI). Clexane® has also been shown to differ from UFH in that it reduces the release of von Willebrand factor, which mediates platelet adhesion to exposed sub-endothelium [38].
Clexane® has a lower binding affinity than UFH to endothelial cells and binds less to plasma proteins. This property is thought to contribute to the higher bioavailability of Clexane® following subcutaneous administration. This may also explain the reduced variability compared with UFH seen in the pharmacodynamic effects of Clexane® [38].
Further information is available in the SPC.
