Summary
The antithrombotic efficacy and duration of action of a single subcutaneous administration
of the selective factor Xa inhibitor recombinant antistasin (rATS) was evaluated in
a rhesus monkey model of mild disseminated intravascular coagulation. rATS (1 mg/kg)
was shown to be fully effective and comparable to standard heparin (1,000 U/kg) in
the suppression of thromboplastin-induced fibrinopeptide A generation for at least
5 h following a single subcutaneous administration. The absorption rate of rATS, as
measured by ex vivo activated partial thromboplastin times (aPTT), mirrored that of
standard heparin exhibiting peak anticoagulant activity between 1 and 2 h post administration.
The anticoagulant effects of a single rATS dose lasted for longer than 30 h maintaining
an aPTT value at least 2-fold higher than baseline. Repeated subcutaneous administrations
of rATS resulted in the generation of fully neutralizing antibodies. These results
suggest that specific factor Xa inhibition may be as effective as standard heparin
in the treatment of venous thrombosis. Due to its antigenicity however, rATS is probably
not suitable for chronic subcutaneous anticoagulant therapy.
