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Recombinant Factor VIIa in postpartum haemorrhage

Recombinant Factor VIIa in postpartum haemorrhage. Dr. Bennet Rajmohan, MRCS (Eng), MRCS Ed Consultant General Surgeon Apollo Speciality Hospital Madurai. On behalf of. Dr. Rohini Sridhar Consultant Haematologist Apollo Speciality Hospital Madurai. Introduction.

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Recombinant Factor VIIa in postpartum haemorrhage

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  1. Recombinant Factor VIIa in postpartum haemorrhage Dr. Bennet Rajmohan, MRCS (Eng), MRCS Ed Consultant General Surgeon Apollo Speciality Hospital Madurai

  2. On behalf of Dr. Rohini Sridhar Consultant Haematologist Apollo Speciality Hospital Madurai

  3. Introduction • Originally developed to treat bleeding in haemophiliacs with antibodies to Factor VIII and IX • Approved in EU for this & also for bleeding in FVII deficiency and Glanzmann thrombasthenia refractory to platelet transfusions • Eptacog alfa (activated), Novoseven

  4. Coagulation cascade

  5. rVIIa – Mechanism of action • Increase in thrombin burst occurs after direct rFVIIa activation of factors IX and X on the surface of activated platelets • Permits formation of fibrin, less susceptible to lysis • Due to increase in Thrombin Activatable Fibrinolysis Inhibitor (TAFI) & Factor XIIIa

  6. The result • Prothrombin time (PT) reduced rapidly • BUT substantial fibrin clot formed only at site of tissue trauma

  7. Dose • 90 -120 mcg / kg IV bolus through any vein, over 2 -5 mins, repeated after 2 hrs if bleeding persists • Half life 2.5 to 3 hrs • IV infusion (without heparin) – steady concentration, 50 – 75% dose reduction

  8. Cost • 1.2 mg - Rs 44,000/- (approx) • 2.4 mg - Rs 87,500/- (approx)

  9. Assessment • Clinical • Lab • PT, APTT  not reliable • Thromboelastogram • Factor VII, Factor VIIa assay

  10. CAUTION • Prior replacement of deficient coagulation factors, red cells, fibrinogen, platelets & avoidance of hypothermia, acidaemia & ongoing surgical bleed • Adverse events (esp. in old age, atherosclerosis, sepsis, crush injury etc) – 25 per 1,00,000 • thrombosis (venous / arterial) • DIC

  11. rVIIa – Advantages • Quick response • Reduces / avoids transfusions • Good safety profile • No risk of viral transmission

  12. Evidence • Price G et al. Use of rFVIIa to treat life threatening non-surgical bleeding in a post-partum patient. BJA 2004;93(2):298-30 • Ahonen J al. rFVIIa for life-threatening post-partum haemorrhage. BJA2005;94(5):592-595 • Marco Ranucci, MD et al. Efficacy & safety of rFVIIa in major surgical procedures. Systematic review & meta-analysis of RCTs. Arch Surg. 2008;143(3):296-304

  13. Ahonen et al. in BJA 2005 • Partial or good response to rFVIIa in 11 out of 12 patients with PPH • In 4 women – subsequent selective arterial embolization – bleeding significantly reduced • Only 3 required ICU admission • Single dose of rFVIIa = transfusion of 50 units of red blood cells, embolization procedure, or 2 days in ICU  may be also cost-effective

  14. Arch Surg. 2008;143(3):296-304 • Meta-analysis of 7 RCTS • rFVIIa reduces no. of patients receiving transfusions • At least 50 mcg / kg dose needed for benefit • Cost benefit ratio favourable in patients needing massive transfusions • No safety concerns in this study

  15. Criteria for rVIIa use • Blood replacement > 1.5 times patient’s blood volume in 24 hrs (i.e. >15 units) • Severe ongoing bleed • Eg: multiple sites, large raw areas despite local control measures • Brisk bleed > 200 ml / hr, inspite of drugs, blood products • Fibrinogen > 1g/L and platelets > 20,000 / mm3

  16. Criteria for rFVIIa (contd) • No surgical correction possible in the immediate foreseeable future • Coagulopathy associated nonsurgical bleed, refractory to conventional treatment • Patient refusing blood products & exsanguination likely • Uterine artery ligation or embolisation or hysterectomy considered

  17. rFVIIa vs embolisation • rFVIIa • Diffuse bleed – not responding to transfusions & uterotonics • No access to interventional radiology • To buy time before shifting to higher centre • More localized & obvious arterial bleed  selective arterial embolization

  18. News Flash • Reuters, Wed Jun 11, 2008 – Novo stops NovoSeven trauma Phase III trial for treatment of bleeding in severe trauma • In February 2007, Novo Nordisk halted regulatory filing for the drug for bleeding in the brain – initial results from a Phase III clinical trial NovoSeven reduces bleeding in the brain but does not improve long-term clinical outcomes • rFVIIa is still useful in Haemophilia

  19. Conclusion • Clinical efficacy of rFVIIa outside the setting of congenital coagulation disorders yet to be defined • Not giving rFVIIa for major bleeding does not equate to substandard care • BUT when conventional, surgical, interventional & blood product support measures have failed, rFVIIa is certainly worth a try

  20. Thank you

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