Effects of nadroparin, enoxaparin, and unfractionated heparin on endogenous factor Xa and IIa formation and on thrombelastometry profiles.

Abstract

Measurements of anti-FXa or anti-FIIa (thrombin) activities are conventional tests for biological monitoring of low molecular weight heparin (LMWH) or unfractionated heparin treatment. It was the aim of our study to assess the anticoagulant efficacy of the LMWHs nadroparin and enoxaparin and that of unfractionated heparin not by the above-mentioned isolated measurements but in the physiological environment of clotting plasma or whole blood. The effects of increasing amounts of nadroparin, enoxaparin, or unfractionated heparin on the time-course of FXa or FIIa formation were investigated in tissue factor activated platelet-poor plasma using a subsampling technique and chromogenic substrates. Moreover, the anticoagulant efficacy of these drugs was also investigated in whole blood triggered by the physiological relevant activator collagen/endogenous thrombin using thrombelastometry. Nadroparin is as efficient as enoxaparin concerning suppression of endogenous FXa or FIIa formation. The two LMWHs are capable of suppressing the formation of FIIa as efficient as that of FXa. Compared with equivalent anti-FXa activity, unfractionated heparin is markedly more efficient in suppressing the formation of FXa and FIIa than the LMWHs. Corresponding results were obtained in whole blood. The anticoagulant efficacy of nadroparin was comparable with that of enoxaparin and the influence of unfractionated heparin on thrombelastometry parameters was markedly stronger than that of the two LMWHs. We conclude that LMWHs are efficient inhibitors not only of endogenous FXa formation but also of endogenous FIIa formation. Under our experimental conditions, the anticoagulant efficacy of nadroparin was comparable with that of enoxaparin but markedly lower than that of unfractionated heparin.