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

R. Al Dieri, R. Wagenvoord, G.W.K. van Dedem, S. Beguin, H.C. Hemker*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    1 Downloads (Pure)

    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 hepar-in (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.
    Original languageEnglish
    Pages (from-to)907-914
    Number of pages8
    JournalJournal of Thrombosis and Haemostasis
    Volume1
    Issue number5
    DOIs
    Publication statusPublished - 2003

    Cite this