Conjectures and refutations on the mode of action of heparins - The limited importance of anti-factor Xa activity as a pharmaceutical mechanism and ayardstick for therapy

Low-molecular-weight heparins (LMWHs), like unfractionated heparin (UFH), e xert their action primarily by accelerating the interaction between antithr ombin (AT) and thrombin. At the levels of aXa activity that are attained in human pharmacology, it does not cause significant (>15%) inhibition of the clotting system. The essential differences between LMWHs and UFH are: (a) LMWHs attain higher plasma concentrations after subcutaneous injection thig h bioavailability), and (b) in contrast to LMWHs, UFH contains very large h eparin molecules with a putative hemorrhagic action. The reputedly higher a Xa activity of LMWH can be shown to be largely due to the absence of Ca2+ u sing the current laboratory methods to estimate this activity. Via this art ifact the apparently high aXa activity of LMWHs is correlated but not relat ed to their favorable pharmacokinetic properties. Consequently dosage guide lines for the use of different LMWHs cannot be based upon their aXa activit y. Until better laboratory methods are available, clinical results are the only reliable guideline to heparin dosage. Copyright (C) 1999 S. Karger AG, Basel.