The limited importance of factor Xa inhibition to the anticoagulant property of heparin in thromboplastin-activated plasma.
The antifactor Xa activities of heparin fractions are widely used as an ex vivo index of their antithrombotic efficacy. Its clinical meaning, however, remains speculative. In the study reported, we measured the effects of standard heparin, a synthetic pentasaccharide heparin (antifactor Xa activity only), and a low molecular weight heparin (LMWH) on factor Xa, factor Va, and thrombin generation in thromboplastin-activated plasma. We clearly demonstrated that the antifactor Xa activity of heparin contributed little in its anticoagulant activity. The inhibition of factor Va generation, dependent on the heparin antithrombin activity only, is of prime importance to the inhibition of thrombin generation in plasma. The inhibition of thrombin generation by the LMWH was comparable with that of standard heparin on the basis of their respective antithrombin specific activities, but not on the basis of their antifactor Xa activities.
Pieters
J
J
Department of Biochemistry, University of Limburg, Maastricht, The Netherlands.
Lindhout
T
T
D001792:Blood Platelets / Q000187:drug effects*; D005165:Factor V / Q000096:biosynthesis; D015943:Factor Va; D015951:Factor Xa; D006493:Heparin / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors; D013917:Thrombin / Q000096:biosynthesis; D013925:Thromboplastin / Q000494:pharmacology*
D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D015842:Serine Proteinase Inhibitors; D015943:Factor Va; D005165:Factor V; D006493:Heparin; D013925:Thromboplastin; D013917:Thrombin; D015951:Factor Xa