New data on the pharmacology of heparin and low molecular weight heparins.
Studies on the pharmacological and pharmacodynamic properties of heparins are complicated by the heterogeneity of heparin preparations. It is important to consider the molecular weight distribution, which may differ from one preparation to another. Molecules with a molecular weight ranging from about 2000 to 5000D are abundant in low molecular weight heparins (LMWHs), while they are present at a very low concentration in standard heparin. The clinical relevance of this difference is not fully understood. Recent work from our laboratory demonstrates that factor VII activation to factor VIIa in vitro is significantly inhibited by heparins. This is another aspect of some importance in understanding the mechanism of action of heparins. The bioavailability and plasma clearance of anti-Xa activity are well documented. In contrast, clear results regarding the bioavailability of anti-IIa activity are still missing. Recent data indicate that the anti-Xa activity of different molecules of heparin does not increase in parallel with the molecular weight of the heparin chain. In contrast, the anti-IIa activity of different molecules of heparin increases in parallel with the molecular weight. This could explain why activated partial-thromboplastin time is less prolonged with LMWHs than with standard heparin. There is growing evidence that anti-Xa activity contributes to the antithrombotic effect of heparins, although it is generally accepted that anti-IIa activity plays a major role. There have been 3 important findings from recent work on the pharmacology of heparins: i) heparin at a very low dose has thrombopoietic activity; ii) in hip surgery, the incidence of heparin-induced thrombocytopenia is significantly lower in patients receiving subcutaneous LMWHs for 2 weeks compared with patients receiving unfractionated heparin; and iii) the risk of osteoporosis with long term treatment with LMWHs seems lower than with standard heparin.
Samama
M M
MM
Laboratoire Central d'Hématologie, Hôpital de l' Hôtel-Dieu de Paris, France.
Bara
L
L
Gouin-Thibault
I
I
D000818:Animals; D000925:Anticoagulants / Q000493:pharmacokinetics / Q000494:pharmacology*; D000990:Antithrombin III / Q000819:agonists; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D010024:Osteoporosis / Q000139:chemically induced; D011485:Protein Binding; D013921:Thrombocytopenia / Q000139:chemically induced
D000925:Anticoagulants; D001798:Blood Proteins; D006495:Heparin, Low-Molecular-Weight; D000990:Antithrombin III; D006493:Heparin