Isolation and characterization of heparin from tuna skins.

This study characterized heparin isolated from tuna skins. Glycosaminoglycans were isolated from tuna skin after digestion using anion exchange resin. Heparin was eluted from the resin by sodium chloride gradient and was further fractionated by acetone fractionation. Anticoagulant activity was determined using the activated partial thromboplastin time and Heptest assays. Potency was determined using amidolytic antifactor IIa and antifactor Xa assays. The presence of heparin in the extracted tuna skin glycosaminoglycans was confirmed using (13)C-nuclear magnetic resonance. The activated partial thromboplastin time and Heptest clotting times were doubled at concentrations of about 4 and 1 microg/mL, respectively. The clotting time prolongation and antiprotease activity induced by tuna heparin was readily neutralized by 25 microg/mL protamine sulfate. These results demonstrate that biologically active heparin with properties similar to clinical grade heparin can be derived from tuna skin, a raw material with otherwise relatively little economic value.

Antiplatelet agents: current drugs and future trends.

Antiplatelet drugs in clinical use are discussed in terms of their mechanisms of action and the relevancy of that to the physiology of platelets and the pathophysiology of arterial thrombosis. Current clinical usage is outlined in detail for each drug. Experimental antiplatelet drugs also are discussed.

Heparin to pentasaccharide and beyond: the end is not in sight.

The 87-year history of heparin began in 1916 when a 26-year-old medical student named Jay McLean startled his mentor William Howell, Professor of Physiology at Johns Hopkins University, by proclaiming that he had discovered "antithrombin." This discovery was so surprising to Howell because he had expected McLean to isolate thromboplastin, a clot-promoting substance from animal tissue. In 1928, Charles Best, M.D., in Toronto, Canada, organized a team of chemists, physiologists, and surgeons to focus on the development of heparin. This group determined which animal tissues were the best source, had performed purification and identification, and had determined pharmacologic properties in vitro. By 1935, they were ready for human trials. By 1941, the group reported a series of 700 patients treated with the glycosaminoglycan called heparin. Meanwhile a critical cofactor, antithrombin, had been discovered at the University of Iowa (Brinkhous, et al). Introduction of newer tests for laboratory monitoring enabled refinement of dosages during the 1960s and 1970s. Its use permitted the development of hemodialysis and cardiopulmonary bypass surgery, and the prophylaxis of deep vein thrombosis in surgical patients. The concept of low-molecular-weight heparin occurred to Dr. Choay and others in France in the late 1970s. During the 1980s and 1990s, the development of low-molecular-weight heparins evolved for both prophylaxis and therapy. The first synthetic product was called the pentasaccharide, named for the five critical sugar units in heparin that bind to antithrombin (1983). Since then, this drug has been studied extensively to prove its clinical efficacy and safety.