Summary
The effects of SP54 on inhibition of thrombin, factor Xa and factor IXa, in the presence
and absence of antithrombin III (At III), have been examined and compared to those
of heparin. SP54 potentiated inhibition of thrombin and Xa by purified At III, but
crossed immunoelectrophoresis data indicated that these effects were mediated by binding
to the enzyme, rather than to At III. Relatively high concentrations of SP54 were
required for inhibition of thrombin and Xa in plasma, but at concentrations less than
2 μg/ml there was a marked suppression of the intrinsic activation of factor X. This
effect was shown to be independent of At III, and to be due largely to inhibition
of factor IXa. Prothrombin activation by factor Xa and phospholipid was also suppressed
by SP54 in the absence of At III, and its effect on the APTT was also shown to be
independent of At III. It is concluded that at relatively low concentrations the anticoagulant
actions of SP54 are mainly due to these At III-independent pathways.
Key words
Heparin - Pentosan polysulphate - SP54 - Mechanism in vitro