Bayer Pharma AG

Essence of this Article

Factor Xa is central to the propagation of coagulation and is an attractive target for the design of new anticoagulants. Two types of Factor Xa inhibitors are commonly used as anticoagulants – direct and indirect Factor Xa inhibitors. Fondaparinux is a synthetic indirect inhibitor of Factor Xa. A limitation of its long-term use for venous thromboembolism (VTE) prevention is the mode of administration by subcutaneous injection. Rivaroxaban, apixaban and edoxaban, all of which are oral agents, directly inhibit Factor Xa. Oral direct Factor Xa inhibitors have many of the properties of an ideal anticoagulant, including oral administration; rapid onset of action; and predictable pharmacokinetics and pharmacodynamics.

Factor Xa Inhibitors

Indirect Factor Xa inhibitors

Fondaparinux is a synthetic indirect inhibitor of Factor Xa.

  • Its structure is based on the natural pentasaccharide contained within heparin and low molecular weight heparins (LMWHs)106
  • It potentiates the rate of neutralization of Factor Xa by antithrombin (AT) and, unlike heparin, does not inactivate thrombin107
  • Fondaparinux does not inhibit Factor Xa bound in the prothrombinase complex and, therefore, does not completely inhibit Factor Xa106
  • As with the heparins, a limitation of long-term use for VTE prevention is the mode of administration by subcutaneous injection106, 107

Direct Factor Xa inhibitors

Rivaroxaban, apixaban and edoxaban directly inhibit Factor Xa and have successfully completed large phase III registrational studies for the prevention of venous thrombosis108

  • Direct Factor Xa inhibitors engage the active site of the Factor Xa molecule and inhibit both free Factor Xa in plasma and Factor Xa attached to the prothrombinase complex106, 107
  • Rivaroxaban, apixaban and edoxaban are oral agents

Oral direct Factor Xa inhibitors have many of the properties of an ideal anticoagulant:106, 107

  • Oral administration
  • Rapid onset of action
  • Predictable pharmacokinetics and pharmacodynamics
FactorXa Propagation Of Coagulation

Factor Xa is central to the propagation of coagulation.109 Activated Factor X, bound as part of the prothrombinase complex on the surface of activated platelets, converts large amounts of prothrombin to thrombin, the so-called ‘thrombin burst.’ PL, phospholipid.

Factor Xa occupies a critical point in the coagulation process 


Sylvia Haas MD

 Factor Xa is positioned at the start of the common pathway of coagulation. As the amount of serine protease is amplified at each step of the cascade, it has been hypothesized that the selective inhibition of coagulation factors above thrombin might be a highly effective antithrombotic strategy.

Sylvia Haas, MD

Professor of Medicine and former Director of the Haemostasis and Thrombosis Research Group at the Institute for Experimental Oncology and Therapy Research, Technical University of Munich, Germany

 


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