Relationship between plasma antifactor Xa activity and the antithrombotic activity of heparins of different molecular mass.
The relationship between the inhibition of venous thrombosis and antifactor Xa (AXa) plasma levels, measured as ex vivo AXa activity at the moment of experimental thrombosis induction, was evaluated in rats treated by different administration routes with different doses of heparins of various molecular masses: unfractionated heparin (UH, 13 kDa), low-molecular-mass heparin (LMM-H, 5kD) and oligo-heparin (OL-H, 2 kD). The AXa activity levels of plasma samples were measured by an amidolytic method and expressed in AXa U/ml. The antithrombotic effect was determined by a vena cava ligature model and expressed as the percent inhibition of thrombus weight. A correlation between the two parameters was determined, regardless of the administration route used. Every heparin requires different AXa plasma levels to develop the same antithrombotic activity: the plasma concentration inducing a 50% protection was 0.09, 0.12 and 0.15 AXa U/ml, for UH, LMM-H and OL-H, respectively. Oligo-H has a significant antithrombotic activity when delivered by the intraileal route and the time course pharmacodynamics showed two phases for the parameters considered: in the second phase, a dissociation between AXa plasma level and antithrombotic effect was observed.
Bianchini
P
P
Opocrin SpA Research Laboratories, Corlo di Formigine, Modena, Italy.
Bergonzini
G L
GL
Parma
B
B
Osima
B
B
D000818:Animals; D004333:Drug Administration Routes; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D013924:Thrombophlebitis / Q000188:drug therapy*
D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin