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.