Heparin mechanism of action
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Heparin is an indirect thrombin inhibitor. Its anticoagulation effect is due to activation of antithrombin III, which in turn inactivates thrombin (factor IIa) and factor Xa. The other mechanism of benefits are due to its inhibition of platelet aggregation
Mechanism of action
- It forms a complexes with antithrombin / AT III (predominantly) and other factors like factor Xa, factors XIIa, XIa, and IXa, that results in a conformational change in antithrombin, converting it from a slow to a rapid inactivator of thrombin.
- Antithrombin has two active sites:
- Reactive center, Arg393-Ser394
- Heparin binding sites
The unfractionated heparins have long saccharide units that are lacking in in the low molecular weight (LMW) heparins, and fondaparinux. These long chains of polysaccharides are required for heparins to bind to both AT and to a binding site on thrombin and formation of a tenary complex. Accordingly, LMW heparins and fondaparinux have less antithrombin activity than does unfractionated heparin [8,9].
- Direct binding to platelets
- Binding to heparin cofactor II (high concentrations) .