Anticoagulation & DOAC History
Traditional anticoagulants such as warfarin, coumarin and heparin are in widespread use. Newer anticoagulants, novel oral anticoagulants (NOACs) or directly acting oral anticoagulants (DOACs) include direct thrombin inhibitor (dabigatran) and factor Xa inhibitor (rivaroxaban and apixaban).
Direct oral anticoagulants (DOACs) is the generic term for a group of anticoagulating substances that act directly against certain coagulation factors and can be taken orally.
Anticoagulation therapy denotes the administration of a drug, the “anticoagulant”, with the aim to inhibit clotting of the patient’s blood. The effect of an anticoagulant is based on the influence to the plasmatic coagulation of the patient, the influence to the plasmatic coagulation factors, to reduce or inhibit clotting activity. Anticoagulants in existence and in development include:
- vitamin K antagonists
- indirect anticoagulants
- direct anticoagulants
For many years, treatment options of venous thromboembolism have been limited to unfractionated heparin or vitamin K antagonists. Recently, many other anticoagulants have been established.
Vitamin K Antagonists
These anticoagulants belong to the group of coumarins. They suppress the vitamin K dependent synthesis of coagulation factors and thus exert an inhibitory effect on the plasmatic coagulation. The dosage form is a daily tablet intake. Regular blood sample drawing and determination of the INR value define the dose.
Heparins (glycosaminoglycans) are only administered parenterally. Their mechanism of action is based on the increase in activity of endogenous antithrombin. The anticoagulant effect is therefore dependent of the patient’s antithrombin. Depending on the molar mass, heparins are distinguished between unfractionated heparin (UFH) and low molecular weight heparin (LMWH). Measuring LMWH levels may be useful in certain situations such as renal failure, underweight / overweight / obesity, bleeding complications thrombosis despite adequate therapy, elderly patients, children and neonates. The pentasaccharide fondaparinux, tradename Arixtra®, is also an indirect factor Xa inhibitor and is prepared completely synthetically.
These drugs intervene directly in the coagulation cascade and inhibit directly specific clotting factors such as Factor Xa and Factor IIa (thrombin). Current research also deals with other factors of the coagulation cascade (e.g. Factor XIa, Factor XIIa and Factor XIIIa).
Factor Xa inhibitors
- Apixaban – tradename Eliquis®
- Rivaroxaban – tradename Xarelto®
- Edoxaban – tradename Lixiana®
- Betrixaban – tradename BEVYXXA®
Factor IIa inhibitors
- Dabigatran – tradename Pradaxa®