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The inhibition of blood coagulation by heparins of different molecular weight is caused by a common functional motif—the C‐domain
Author(s) -
Al Dieri R.,
Wagenvoord R.,
Van Dedem G. W. K.,
Béguin S.,
Hemker H. C.
Publication year - 2003
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1046/j.1538-7836.2003.00211.x
Subject(s) - chemistry , antithrombin , partial thromboplastin time , thrombin , low molecular weight heparin , heparin , coagulation , pharmacology , biochemistry , medicine , platelet
Summary. 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 Ca 2+ ‐ 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.