Dabigatran and the parenteral direct thrombin inhibitors
Fibrin and control · detail · Direct IIa Idarucizumab
Dabigatran etexilate is an oral prodrug that reversibly and competitively blocks the active site of thrombin, inhibiting both free and clot-bound thrombin without needing antithrombin. Argatroban and bivalirudin do the same parenterally and are the agents of choice when heparin cannot be used.
Traced from the start
- Tissue factor and the extrinsic triggerVitamin K cycle and gamma-carboxylation
- Contact activation system (factor XII, prekallikrein, high-molecular-weight kininogen)
- Subendothelial collagen and von Willebrand factor
- Tissue factor-factor VIIa complex (extrinsic tenase)Factor IXaFactor VIIIa and its von Willebrand factor carrierActivated platelet phospholipid surface
- Factor XaFactor VaProthrombin (factor II)
- Thrombin (factor IIa)
- Dabigatran and the parenteral direct thrombin inhibitors
Detail
- Mechanism
- Direct, reversible, competitive active-site inhibition of thrombin
- Pharmacokinetics
- About 80% renally cleared, so it is avoided when creatinine clearance is below 30 mL/min; half-life 12-17 hours
- Effect on tests
- Markedly prolongs the thrombin time — a normal thrombin time effectively excludes clinically relevant dabigatran — and prolongs the APTT variably; quantify with a dilute thrombin time or ecarin clotting time
- Reversal
- Idarucizumab, a monoclonal antibody fragment; dabigatran is also dialysable, unlike the Xa inhibitors
- Parenteral agents
- Argatroban, hepatically cleared and preferred in renal failure, and bivalirudin
When it goes wrong
Heparin-induced thrombocytopenia requiring ongoing anticoagulation
Use argatroban or bivalirudin; every form of heparin, including line flushes, must be stopped
Practise this structure
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