Coagulation inhibition capacities of low-molecular mass and unfractionated heparin, as determined by thrombin generation

Abstract

The common unfractionated heparin preparations (UFH) accelerate inhibition of most of the enzymes in the coagulation cascade, while low-molecular mass heparin (LMMH) mainly accelerates inhibition of activated coagulation factor X (FXa). The present study addresses the question of whether LMMH may be a weaker anticoagulant than UFH when the two preparations are added to plasma with equal FXa inhibitory activities. Normal and coagulation factor VIII (FVIII)-deficient plasma was used. Thrombin generation was determined by assaying the formation of the thrombin-antithrombin complexes (TAT) and of fibrinopeptide A (FPA), two parameters that showed a strong positive correlation. At a heparin concentration of 0.5 or 1.0 FXa-inhibiting IU/ml, the formation of TAT and FPA was substantial and always much more increased with LMMH than with UFH. At 4.0 FXa-inhibiting IU/ml, no FPA was generated, but traces of thrombin were. In recalcified FVIII-deficient plasma (one of the batches containing FVIII antibodies), more TAT was formed with 0.1 FXa-inhibiting IU/ml LMMH than with UFH with the same FXa-inhibiting activity. It is concluded that LMMH is a weaker anticoagulant than UFH, partly because of a poor thrombin inhibition capacity which facilitates acceleration of coagulation by FVIII activation and partly because of a poor inhibition of enzymes preceding the prothrombinase stage, both mechanisms leading to increased enzymatic activity above the prothrombin stage. As judged from the higher degree of thrombin generation with LMMH than with UFH, there is no support for the assumption that LMMH is as good an antithrombotic agent as UFH is, without reducing the haemostatic capacity as much as UFH does.