Summary
We investigated the effect on thrombin generation in plasma of the pentasaccharide
that represent the AT II/binding site in heparin. This compound has no effect on the
breakdown of thrombin in plasma. It dose-dependently inhibits the formation of thrombin
in both the intrinsic and the extrinsic pathway. If coagulation is triggered by the
complete prothrombinase complex (phospholipid – factor Va – factor Xa) under conditions in which the large majority of factor Xa is bound to the complex, the inhibition of prothrombinase activity is only minor.
If no factor Va is present or if the prothrombinase activity is triggered by adding complete tenase
(PL-FVIIIa-FIXa) or incomplete tenase (PLFIXa) to the plasma the inhibition by pentasaccharide is of the same magnitude as that
in the intrinsic or extrinsic system.
We conclude that the pentasaccharide inhibits blood coagulation by katalysing the
inactivation of free factor Xa. In contrast to classical heparin it does inhibit the peak of thrombin formation
in platelet rich plasma, probably because it is less subject to inactivation by heparin
binding proteins from platelets than classical heparin is.
Keywords
Heparin - Pentasaccharide - Thrombin generation - Factor X
a
