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Biochemistry

Both forms of heparin accelerate the inhibitory activity of antithrombin. However, the mechanisms of the complex formation with the enzymes are different.

a) Unfractionated heparin (UFH)

Unfractionated heparin has binding sites for thrombin and antithrombin. After both molecules have bound to the heparin chain a rapid complex formation between thrombin and antithrombin takes place, due to conformational changes in both molecules after heparin binding. Subsequently, UFH dissociates from the complex. UFH / antithrombin also inhibits factor Xa, which itself does not bind to UFH.

b) Low molecular weight heparin (LMWH)

The considerably shorter molecule of LMWH has a binding site only for antithrombin, but none for thrombin. Therefore the inhibition of thrombin by antithrombin only takes place very slowly in the presence of LMWH, while the inhibition of factor Xa is considerably accelerated, as it is by UFH.

Clinical significance

Heparins are employed as anticoagulants in the therapy and prophylaxis of thromboembolic disease. Possible complications of a heparin therapy are bleeding and heparin induced thrombocytopenia (HIT). For this reason, it may be advisable to monitor the heparin concentration during therapy. Monitoring is generally not necessary during prophylaxis. However, for prophylaxis during pregnancy monitoring may be advantageous. In the case of inexplicable bleeding, which occur very rarely, it is advisable to document the anti-factor Xa activity.

Indication

• Monitoring of high dose heparin therapy
• Monitoring heparin therapy in renal insufficiency
• Determination of the anti-factor Xa activity at the onset of treatment with LMW heparin in order to assess the optimal therapy.

1. Hirsh J. Drug therapy: Heparin. New Engl J Med 324, 1565-1574, 1991.
2. Hirsh J. Low molecular weight heparin. Thromb Haemost 70, 204-307, 1993.
3. Schuster B. Monitoring of anticoagulants. Hämostaseologie 29, 268-273, 2009.