The inhibition of blood coagulation by heparins of different molecular weight is caused by a common functional motif
| Autor: | Robert Wagenvoord, G W K van Dedem, R. Al Dieri, H. C. Hemker, Suzette Beguin |
|---|---|
| Přispěvatelé: | Biochemie |
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Molar concentration
medicine.drug_class Amino Acid Motifs Pharmacology Structure-Activity Relationship Thrombin medicine Humans Blood Coagulation Dose-Response Relationship Drug medicine.diagnostic_test Heparin Chemistry Antithrombin Anticoagulant Anticoagulants Hematology Blood proteins Protein Structure Tertiary Molecular Weight Biochemistry Molar mass distribution Partial Thromboplastin Time circulatory and respiratory physiology medicine.drug Partial thromboplastin time |
| Zdroj: | Journal of Thrombosis and Haemostasis, 1(5), 907-914. Wiley |
| ISSN: | 1538-7933 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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