No abstract

Antithrombin drugs represent a wide group of natural agents, recombinant agents equivalent to some of the naturally occurring proteins, and synthetic agents. This group of drugs is characterized by marked structural and functional heterogeneity. Several of these drugs are currently in various phases of development. Argatroban represents the first clinically approved antithrombin agent, which was made available in Japan several years ago. Two recombinant hirudin preparations, Revasc (Novartis) and Refludan (Aventis), are available for postsurgical DVT prophylaxis and alternate anticoagulant use in patients with heparin-induced thrombocytopenia. A synthetic antithrombin agent based on the combined structures of hirudin and antithrombin peptides, hirulog (Bivalirudin), is undergoing clinical trials in cardiovascular indications. Additional studies on the hirudins are being carried out to test their efficacy as surgical and interventional anticoagulants as replacements for heparin. However, the need for a proper antagonist is one of the limiting factors for the optimal development of hirudin in this indication. Several of the synthetic thrombin inhibitors are also being developed for oral use for the prophylaxis of DVT in surgical patients. Since the therapeutic index of thrombin inhibitors is narrower than that of heparin, this route may not be an optimal approach for the development of these agents. Despite several unresolved developmental issues, the thrombin inhibitors provide a useful alternative to heparin anticoagulation and may prove to be useful in validated clinical use.

No abstract

Red blood cell (RBC) replacement solutions are being developed as alternatives to allogeneic RBC use in blood transfusions in the treatment of massive trauma, to achieve hemodynamic stability during elective surgery, and to increase oxygen-carrying capacity in anemia. Hemoglobin-based oxygen carrier (HBOC)-201 (Biopure Corp.) is a purified, sterile, isosmotic glutaraldehyde-polymerized bovine hemoglobin. Because this product is acellular, blood components containing this substance appear hemolyzed. This study reports on the interferences produced by the presence of HBOC-201 in a variety of clinical assays. This product was added in vitro at concentrations up to 60 g/L (6.0 g/dL) to normal human serum, plasma, or whole blood before testing for serum chemistries, coagulation profiles, and hematology and blood bank assays. In addition, a set of normal human sera containing HBOC-201 was supplemented with various therapeutic drugs and assayed for these agents. The results of these studies demonstrate that the presence of HBOC-201 in blood components does not result in significant analytical interference that would be of concern with many clinical assays at HBOC-201 concentrations encountered during routine clinical use of this RBC replacement solution in patients.