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@1993 Elsevier Science Publishers B V All rights rcseruedVasculu Medicine H. Bocca.lon. editor.
Low molecular weight heparins - their mode of action in plasma
and its consequences for the clinical laboratorySuzette Bdguin and H. Coenraad HemkerDepartment of Biochemistry, Cardiovascular Research Institute and University of Limburg, Maastricht, TheNetherlands
IntroductionUnfractionated heparin (UFH) has been with us as a drug since the 1930s and lowmolecular weight heparins (LMWH) for some 20 years. This means that there is a fairamount of established practice in dealing with these drugs. Research in the last fewyears has made it clear that some of the traditional ways of approaching hcparins arenot necessarily the most adequate ones. lndeed there is a consrderable amou'rt ofconfusion arising from attempts to define LMWHs in terms that are adequate to dealwith UFH. In this article we propose an approach to the clinical chemistry of heparinsbased on recent biochemical data. We will indicate what the differences are with theexisting practice and we will show how existing practice can be brought in line withthe new approach.Types of heparinHeparin is a mixture of linear polysaccharides consisting of alternating iduronic acidor glucoronate units and N-acetylglucoseamine units joined by glycosidic l-4linkages. Most of the N-acetyls of the glucosamine are replaced by N-sulfo groups.Most iduronates are O-sulfated in their 2-position, most glucosamines in their 6-position. The result is that there is a wide variety of different possible mono-saccharides. They occur in almost random order and the chain lengths can vary fromfive to 100 or more. This chemical diversity is reflected in different biologicalactivities.In order to be active in antithrombin III (ATIII) dependent reactions (see below),heparin has to bind to ATIII via a specific pentasaccharide sequence. Heparins thatcontain this sequence we call high affinity material (HAM). The low affinity material(LAM) as such is not active in ATIII dependent reactions but may influence theaction of HAM by replacing it in nonspecific reactions (see below). The HAM comesin two kinds: the material with a chain length of 5-17 monosaccharide units (MW1700-5400) which is not capable of catalysing ATIII dependent thrombin activation.We therefore call it below critical chain length material (BCLM). The HAM longer
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