Goodman & Gilman's Pharmacology > XI. Drugs Acting on the Blood and the Blood-Forming Organs > Chapter 54. Blood Coagulation and Anticoagulant, Thrombolytic, and Antiplatelet Drugs Philip W. Majerus and Douglas M. Tollefsen

Parenteral Anticoagulants

"Heparin is a glycosaminoglycan found in the secretory granules of mast cells. It is synthesized from UDP-sugar precursors as a polymer of alternating D-glucuronic acid and N-acetyl-D-glucosamine residues (Figure 54–4) (Sugahara and Kitagawa, 2002). About 10 to 15 glycosaminoglycan chains, each containing 200 to 300 monosaccharide units, are attached to a core protein and yield a proteoglycan with a molecular mass of 750,000 to 1,000,000 daltons. The glycosaminoglycan then undergoes a series of modifications, which include the following: N-deacetylation and N-sulfation of glucosamine residues, epimerization of D-glucuronic acid to L-iduronic acid, O-sulfation of iduronic and glucuronic acid residues at the C2 position, and O-sulfation of glucosamine residues at the C3 and C6 positions. Each of these modifications is incomplete, yielding a variety of oligosaccharide structures. After the heparin proteoglycan has been transported to the mast cell granule, an endo--D-glucuronidase degrades the glycosaminoglycan chains to fragments of 5000 to 30,000 daltons (mean, about 12,000 daltons or 40 monosaccharide units) over a period of hours.High doses of heparin can interfere with platelet aggregation and thereby prolong bleeding time. It is unclear to what extent the antiplatelet effect of heparin contributes to the hemorrhagic complications of treatment with the drug...."