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Direct Thrombin Inhibitors

This section covers the role of thrombin in coagulation, and discusses the use of direct thrombin inhibitors as anticoagulants

  • Thrombin plays a key role in coagulation1
  • It is produced in small amounts in the initiation phase and large amounts in the propagation phase2
  • Thrombin is essential for the amplification of coagulation and fibrin formation1
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Thrombin plays a key role in coagulation.1 During the propagation phase, activated Factor X converts large amounts of prothrombin to thrombin, initiating a ‘thrombin burst’

PL, phospholipid

  • Dabigatran is a competitive, reversible direct thrombin inhibitor3
    • It inhibits free thrombin, fibrin-bound thrombin and thrombin-induced platelet aggregation
    • Inhibition of thrombin prevents the conversion of fibrinogen to fibrin and thus clot formation
    • Dabigatran is orally administered as the prodrug dabigatran etexilate, which is converted to the active form in plasma and in the liver
  • Dabigatran is approved in Europe in adults for:3
    • Prevention of VTE in patients undergoing elective hip or knee replacement surgery
    • Treatment of DVT and PE and prevention of recurrent DVT and PE (following initial parenteral anticoagulation for at least 5 days)
    • Prevention of stroke and systemic embolism in patients with NVAF with ≥1 risk factors
References

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