Pharmacotherapeutic aspects of unfractionated and low molecular weight heparins. 1990

M Verstraete
Centre for Thrombosis and Vascular Research, University of Leuven, Belgium.

Standard unfractionated heparin is a mixture of mucopolysaccharide chains of various length that may vary from 5000 to 30,000 daltons. Heparin is only effective as an anticoagulant in the presence of a plasma protein termed antithrombin III, with which it forms a complex. High- and low-affinity heparin are 2 types that readily bind or do not bind, respectively, to antithrombin III. The pharmacokinetics of unfractionated heparin are compatible with a model based on the combination of a saturable and a linear mechanism. The primary indication for intravenous infusion of conventional heparin is to prevent extension of an established arterial, venous or intracardiac thrombus. The average requirement is 400 U/kg/24h. Subcutaneous administration of 5000U of concentrated unfractionated heparin, administered every 8 or 12 hours, is effective and safe in the prevention of postoperative venous thrombosis and pulmonary embolism in patients at medium thrombotic risk. Adequate prophylaxis is also obtained in patients at high thrombotic risk if 5000U of heparin combined with 0.5mg dihydroergotamine is given subcutaneously 3 times daily, or by monitoring the 3 subcutaneous doses of heparin in order to maintain an adjusted activated partial thromboplastin time (APTT) of around 50 to 70 seconds. Low molecular weight heparins have been produced by a variety of techniques and their molecular weights range from 3000 to 9000 daltons. These preparations have a ratio of anti-factor Xa activity to anti-factor IIa activity of about 4, while the ratio for unfractionated heparin is 1. After intravenous administration of low molecular weight heparin, the half-life of the anti-factor Xa activity is considerably longer than for unfractionated heparin, while the anti-factor IIa half-lives are similar. In contrast to unfractionated heparin, low molecular weight heparin is completely absorbed after subcutaneous administration and its biological half-life is almost twice as long. In spite of certain differences with regard to the ratio between factor Xa and IIa inhibition, the various low molecular weight preparations show a rather similar absorption pattern. The bioavailability of all low molecular weight heparin fractions is substantially higher than that of unfractionated heparin, which renders their use more simple. Low molecular weight heparins less readily enhance platelet aggregation although there is no evidence that low molecular weight heparins are less antigenic or that they do not interact with platelet IgGFc receptor. A lower bleeding incidence for equivalent antithrombotic efficacy of fractionated heparins when compared to unfractionated heparins has yet to be established in humans.(ABSTRACT TRUNCATED AT 400 WORDS)

UI MeSH Term Description Entries
D006493 Heparin A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Heparinic Acid,alpha-Heparin,Heparin Sodium,Liquaemin,Sodium Heparin,Unfractionated Heparin,Heparin, Sodium,Heparin, Unfractionated,alpha Heparin
D006495 Heparin, Low-Molecular-Weight Heparin fractions with a molecular weight usually between 4000 and 6000 kD. These low-molecular-weight fractions are effective antithrombotic agents. Their administration reduces the risk of hemorrhage, they have a longer half-life, and their platelet interactions are reduced in comparison to unfractionated heparin. They also provide an effective prophylaxis against postoperative major pulmonary embolism. LMWH,Low-Molecular-Weight Heparin,Low Molecular Weight Heparin,Heparin, Low Molecular Weight
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

M Verstraete
January 1990, Acta chirurgica Scandinavica. Supplementum,
M Verstraete
June 2013, Cardiovascular & hematological agents in medicinal chemistry,
M Verstraete
November 2007, Clinical advances in hematology & oncology : H&O,
M Verstraete
August 2001, European heart journal,
M Verstraete
October 2007, Clinical advances in hematology & oncology : H&O,
M Verstraete
September 2002, Thrombosis and haemostasis,
M Verstraete
December 2001, Adverse drug reactions and toxicological reviews,
M Verstraete
April 2019, Journal of investigational allergology & clinical immunology,
Copied contents to your clipboard!