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J Thromb Haemost. 2003 May;1(5):907-14.

The inhibition of blood coagulation by heparins of different molecular weight is caused by a common functional motif--the C-domain.

Author information

1
Synapse BV, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands.

Abstract

BACKGROUND:

Heparins in clinical use differ considerably as to mode of preparation, molecular weight distribution and pharmacodynamic properties.

OBJECTIVES:

Find a common basis for their anticoagulant action.

METHODS:

In 50 fractions of virtually single molecular weight (Mr), prepared from unfractionated heparin (UFH) and four low-molecular-weight heparins (LMWH), we determined: (i) the molar concentration of material (HAM) containing the antithrombin binding pentasaccharide (A-domain); (ii) the specific catalytic activity in thrombin and factor Xa inactivation; (iii) the capacity to inhibit thrombin generation (TG) and prolong the activated partial thromboplastin time (APTT). We also calculated the molar concentration of A-domain with 12 sugar units at its non-reducing end, i.e. the structure that carries antithrombin activity (C-domain).

RESULTS:

The antithrombin activity and the effects on TG and APTT are primarily determined by the concentration of C-domain and independent of the source material (UFH or LMWH) or Mr. High Mr fractions (>15 000) are less active, probably through interaction with non-antithrombin plasma proteins. Anti-factor Xa activity is proportional to the concentration of A-domain, it is Ca2+- and Mr-dependent and does not determine the effect on TG and APTT.

CONCLUSION:

For any type of heparin, the capacity to inhibit the coagulation process in plasma is primarily determined by the concentration of C-domain, i.e. the AT-binding pentasaccharide with 12 or more sugar units at its non-reducing end.

PMID:
12871355
[Indexed for MEDLINE]
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