Factor VIIa (NovoSeven RT)

Indications

FDA-Approved Indications

  • Treatment or Prevention of Bleeding in Patient with Hemophilia A with Inhibitor to Factor VIII (see Hemophilia A, [[Hemophilia A]])
  • Treatment or Prevention of Bleeding in Patient with Hemophilia B with Inhibitor to Factor IX (see Hemophilia B, [[Hemophilia B]])
  • Treatment or Prevention of Bleeding Episodes in Patients with Acquired Hemophilia
  • Treatment or Prevention of Bleeding Episodes in Patients with Congenital Factor VII Deficiency (see Factor VII Deficiency, [[Factor VII Deficiency]])

Off-Label Indications

  • General Comments
    • Cochrane Systematic Review (2012) [MEDLINE]
      • Main Findings: the effectiveness of recombinant factor VIIa as general hemostatic drug, either prophylactically or therapeutically, remains unproven
        • The results indicate increased risk of arterial events in patients receiving recombinant factor VIIa
        • The use of recombinant factor VIIa outside its current licensed indications should be restricted to clinical trials
  • Anticoagulant Reversal
    • IIb/IIIa Inhibitors (see IIb IIIa Inhibitors, [[IIb IIIa Inhibitors]])
    • Coumadin (see Coumadin, [[Coumadin]])
      • Factor VIIa has been used to more rapidly reverse coumadin anticoagulation than FFP
      • In addition, since the INR does not fully reflect the mechanism of action of factor VII in vivo, Factor VIIa may provide benefit over simply correcting the INR with FFP
    • Factor Xa Inhibitors (see Factor Xa Inhibitors, [[Factor Xa Inhibitors]])
      • Fondaparinux (Arixtra) see Fondaparinux, [[Fondaparinux]])
      • Rivaroxaban (Xarelto) (see Rivaroxaban, [[Rivaroxaban]])
    • Low Molecular Weight Heparins
      • Dalteparin (Fragmin) (see Dalteparin, [[Dalteparin]])
      • Enoxaparin (Lovenox) (see Enoxaparin, [[Enoxaparin]])
      • Tinzaparin (Innohep) (see Tinzaparin, [[Tinzaparin]])
    • Thrombin Inhibitors (see Factor IIa Inhibitors, [[Factor IIa Inhibitors]])
      • Dabigatran (Pradaxa) (see Dabigatran, [[Dabigatran]])
    • Tissue Factor Inhibitors
  • Bernard-Soulier Syndrome (see Bernard-Soulier Syndrome, [[Bernard-Soulier Syndrome]]): has been used to treat patients with platelet refractoriness
  • Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]])
  • End-Stage Liver Disease (ESLD) (see End-Stage Liver Disease, [[End-Stage Liver Disease]])
  • Factor XI Deficiency (see Factor XI Deficiency, [[Factor XI Deficiency]])
  • Glanzmann’s Thrombasthenia (see Glanzmann’s Thrombasthenia, [[Glanzmanns Thrombasthenia]]): has been used to treat patients with platelet refractoriness
  • Hemorrhagic Complications of Stem Cell Transplantation (see Bone Marrow Transplant, [[Bone Marrow Transplant]])
  • Massive Uncontrolled Hemorrhage
  • Platelet Function Defects
  • Surgery-Associated Hemorrhage
  • Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]])
  • Trauma-Associated Hemorrhage
  • Von Willebrand Disease (see Von Willebrand Disease, [[Von Willebrand Disease]]): in type 1, 2a, and 3 with antibodies against vWF

Pharmacology

Recombinant Factor VIIa

  • In Hemophilias: platelet-bound Factor VIIa partially restores platelet surface factor X activation
  • In Non-Hemophiliac Conditions: platelet-bound Factor VIIa increases activation of both factor IX and factor X and increases thrombin generation above normal levels -> increased thrombin enhances platelet activation and accumulation (including dysfunctional platelets)

Administration

  • IV
    • End-Stage Liver Disease: doses reported range from 5-120 ug/kg
  • Half-Life of Recombinant Factor VIIa: 2 hrs
    • Note: the half-life of normal factor VIIa is 4-6 hrs
  • Cost for Single 90 ug/kg IV Dose (US): $4500

Adverse Effects

Hematologic Adverse Effects

  • General Comments
    • Overall Rate of Events (most with off-label use): ranges from 1%-9.8%
    • Product packaging indicates that the rate of thrombotic events is 4% in patients with acquired hemophiia
    • Product packaging indicates that the rate of thrombotic events is 0.2% of bleeding episodes in patients with congenital hemophiia
  • Arterial Thrombosis:
  • Venous Thrombosis:

Immunologic Adverse Effects


References

  • Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia. Cochrane Database Syst Rev. 2012 Mar 14;3:CD005011. doi: 10.1002/14651858.CD005011.pub4 [MEDLINE]