Abstract
The introduction of low-molecular-mass heparins (LMMHs) has added a new dimension
to the prophylactic and therapeutic management of thromboembolic disorders. These
agents are now globally accepted as drugs of choice for postsurgical prophylaxis of
deep vein thrombosis (DVT). Currently, the LMMHs are being developed for various therapeutic
and cardiovascular indications. Reviparin is an optimized LMMH prepared by controlled
nitrous acid digestion of porcine mucosal heparin. This drug has been developed utilizing
validated procedures and exhibits a relatively narrow molecular mass distribution
in contrast to most other commercially available LMMHs. The specific activity in the
anticoagulant assays is approximately 40 U/mg whereas the specific activity in amidolytic
anti-Xa assays is approximately 100 anti-Xa U/mg. Reviparin is capable of producing
dose- and time-dependent antithrombotic effects in animal models of thrombosis. Although
ex vivo anticoagulant effects are initially observed at dosages that are antithrombotic,
this agent has been found to produce sustained antithrombotic effects when ex vivo
anticoagulant actions are not measurable. Repeated administration of this LMMH induces
progressively stronger antithrombotic effects. This drug has also been found to release
tissue factor pathway inhibitor (TFPI) following both intravenous (IV) and subcutaneous
(SC) administration. The studies included in this article are designed to provide
additional data on the molecular profile using new calibration methods and additional
results on pharmacologic studies. In particular, the release of TFPI following IV
and SC administration to nonhuman primates is described. The effect of repeated administration
of Reviparin mimicking the postsurgical prophylaxis of DVT is also reported in terms
of any augmentation of the antithrombotic or hemorrhagic effects of this agent.
Keywords:
Low-molecular-mass heparin (LMMH) - deep vein thrombosis - Reviparin - tissue factor
pathway inhibitor (TFPI) - animal experiments
