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rFactor VIIa

rFactor VIIa. Dr S Kumar Cardiac Anesthesiologist Meenakshi Mission Hospital and Research Centre Madurai. Haemorrhage control. Controlling bleeds and maintaining blood volume are the primary concerns in bleeding management The treatment of bleeding is to stop the bleeding.

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rFactor VIIa

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  1. rFactor VIIa Dr S Kumar Cardiac Anesthesiologist Meenakshi Mission Hospital and Research Centre Madurai

  2. Haemorrhage control Controlling bleeds and maintaining blood volume are the primary concerns in bleeding management The treatment of bleeding is to stop the bleeding

  3. The 12 P’s of Clinical Hemostasis “ApplyPressure withPacksor Pads, havePatience,suture withProlene(or whatever).GivePlatelets, fresh frozenPlasma, Protamine(to reverse heparin),andPackedcells(if still bleeding),call theProfessorfor help… if he cant help-Pray…thatyou will not meet your patient at thePostmortem.” Dr Ahmad Assalia

  4. The Bloody Vicious Cycle Bleeding CoagulopathyTransfusion Hypothermia Acidosis!!

  5. Why not multiple transfusion? • Increased risk of infection • Increased risk of multiple organ failure (MOF) • No extra benefit - in terms of in-hospital and 60 day mortality, development of MI, pulmonary oedema & ARDS

  6. What does rFVIIa do? STOPS BLEEDING FAST!!!

  7. Outline • What is Recombinant Factor VIIa(rFVIIa)? • Why it was introduced? • How is it prepared? • How does it act? • For what can Factor VIIa be used? • What is the dosage? • Is it safe ? • What is NICE Registry? • How is rFactor VIIa useful in Cardiac Surgery?

  8. What is rFVIIa? • It is a vitamin K-dependent glycoprotein consisting of 406 amino acid residues (MW 50 K Dalton). • It is structurally similar to human plasma-derived Factor VIIa. • It is intended for promoting hemostasis by activating the extrinsic pathway of the coagulation cascade.

  9. Outline • What is Recombinant Factor VIIa(rFVIIa)? • Why it was introduced? • How is it prepared? • How does it act? • For what can Factor VIIa be used? • What is the dosage? • Is it safe ? • What is NICE Registry? • How is rFactor VIIa useful in Cardiac Surgery?

  10. Why it was introduced? • rFVIIa originally developed for the treatment of acquired inhibitors associated with hemophilia. • It has been successfully used for bleeding due to thrombocytopathy, extensive trauma and a variety of surgical procedures.

  11. Outline • What is Recombinant Factor VIIa(rFVIIa)? • Why it was introduced? • How is it prepared? • How does it act? • For what can Factor VIIa be used? • What is the dosage? • Is it safe ? • What is NICE Registry? • How is rFactor VIIa useful in Cardiac Surgery?

  12. How is it prepared? • FVIIa gene cloned & transfected to BHK cells which produces FVII. • Structurally similar to plasma-derived human FVIIa

  13. Outline • What is Recombinant Factor VIIa(rFVIIa)? • Why it was introduced? • How is it prepared? • How does it act? • For what can Factor VIIa be used? • What is the dosage? • Is it safe ? • What is NICE Registry? • How is rFactor VIIa useful in Cardiac Surgery?

  14. How does it act? Initiation Amplification Propagation Thrombin burst Thrombin II

  15. 2. Amplification phase 1. Initiation phase 3. Propagation phase

  16. N7 - MOA N7 - MOA

  17. Effect on Coagulation • There is a significant reduction in PT/ INR. • Clinically insignificant reduction in APTT. • No major effect on platelets.

  18. Outline • What is Recombinant Factor VIIa(rFVIIa)? • Why it was introduced? • How is it prepared? • How does it act? • For what can Factor VIIa be used? • What is the dosage? • Is it safe ? • What is NICE Registry? • How is rFactor VIIa useful in Cardiac Surgery?

  19. For what can Factor VIIa be used? • Hemophilia with inhibitors • Glanzmann’s Thrombasthenia • Factor VII deficiency • Bleeding in Trauma • Cardiac surgery bleeds • PPH • Liver/UGI Bleeding • Anticoagulant toxicity reversal

  20. Outline • What is Recombinant Factor VIIa(rFVIIa)? • Why it was introduced? • How is it prepared? • How does it act? • For what can Factor VIIa be used? • What is the dosage? • Is it safe ? • What is NICE Registry? • How is rFactor VIIa useful in Cardiac Surgery?

  21. Dosage Low dose (1.0 mg = 10-20 g/kg) Intermediate dose (2.0 mg = 30-50g/kg) High dose (4.0 mg or more = 70-90 g/kg)

  22. Cost • 1 mg - Rs 43,450 2 mg - Rs 86,900 • It is expensive but it should be weighed against the possible benefits • Effective therapy can reduce the incidence of multiple transfusions & their ill effects.

  23. Factor VIIa Half Life The mean elimination half life is 3.8-5.8 hrs (only 1.3 hrs in children)

  24. Outline • What is Recombinant Factor VIIa(rFVIIa)? • Why it was introduced? • How is it prepared? • How does it act? • For what can Factor VIIa be used? • What is the dosage? • Is it safe ? • What is NICE Registry? • How is rFactor VIIa useful in Cardiac Surgery?

  25. Is it safe to use Factor VIIa? • Recombinant product of non-human origin • No risk of viral transmission • Hypersensitive reactions rare • Estimated incidence of thromboembolism in patients treated with rFactor VIIa for conditions other than haemophilia-1.4% • With 800mcg/kg administration, no toxic effects reported

  26. Outline • What is Recombinant Factor VIIa(rFVIIa)? • Why it was introduced? • How is it prepared? • How does it act? • For what can Factor VIIa be used? • What is the dosage? • Is it safe ? • What is NICE Registry? • How is rFactor VIIa useful in Cardiac Surgery?

  27. Why NICE Registry? NICE Registry – The journey so far... NICE Registry Demographic data Chronicle Indications and doses Overall efficacy and survival data Impact of NovoSeven® outcome Track record, 2006–2010

  28. Why This Registry? NovoSeven® in Critical care Evaluation (NICE Registry) in April 2006 Off label uses – Evidence based indications No consensus in dose and duration Practice based collection of data Aim: To see if it would be possible to gather new information and endorse the available information

  29. Demographic data – NICE Registry April ´06 to till Feb ´10 Median Range (in years) Age 40 0.5 – 91 193 121 Total – 314

  30. NovoSeven® Overall efficacy April ´06–Feb ´10 n=314 13.9% 62.8% Bleeding reduced Bleeding stopped 12.3% Minimal bleeding 11.0% Bleeding did not reduce Haemostatic response to NovoSeven® was seen in 89% of cases

  31. NICE Registry • NICE registry – Is a 1st step towards the collection of data in emerging indications of NovoSeven® • Median dose of NovoSeven® – 60 µg/kg • Highest in DHF (77.5 µg/kg) • Least in cardiac surgery (40 µg/kg) • Haemostatic response with NovoSeven® was seen in 89% of cases with a few adverse events • The overall survival rate with NovoSeven® usage was 70% • Clinicians with impression of positive impact – 74% • Reduction in the use of blood component after NovoSeven® therapy reported in medical and surgical causes of bleeding

  32. Outline • What is Recombinant Factor VIIa(rFVIIa)? • Why it was introduced? • How is it prepared? • How does it act? • When can Factor VIIa be used? • For what can Factor VIIa be used? • What is the dosage? • Is it safe ? • What is NICE Registry? • What is the role in Cardiac Surgery?

  33. Bleeding Problems in Cardiac Surgery-Possible Causes • Platelet dysfunction • Hyperfibrinolysis in the re-transfused blood • Exposure of blood to artificial surfaces • Haemodilution • Consumption of coagulation factors & platelets • Hypothermia

  34. Bleeding Problems in Cardiac Surgery Treatment Strategies • Mechanical techniques(e.g.cell salvage) • Pharmacological techniques • EACA, TEA, Desmopressin, Aprotinin.

  35. Effect of rFVIIa • Blood loss was at least 25-35% less after the administration of the rFVIIa • Blood product & Component therapy usage was reduced

  36. Safety • A particularly important safety concern with the use of rFVIIa in cardiac surgery is the potential for inappropriate clotting due to increased tissue factor expression. • It’s true efficacy & safety profile will not be known until further appropriately powered randomized trials are performed.

  37. MMHRC EXPERIENCE 4 Cases in Cardiac Surgery Tetralogy Of Fallot - 1 Acute Dissecting Aortic Aneurysm - 2 CABG - 1 Bleeding subsided in all. One patient survived. Rest died due to MODS

  38. Conclusion • Absence of high-quality data & laboratory tests able to predict response • Good Safety Profile with favourable risk-to-benefit ratio • Off-label use of recombinant factor VIIa be a ‘last resort’

  39. Words of Wisdom “Blood transfusion is like marriage; it should not be entered upon lightly, unadvisedly or wantonly or more often than is absolutely necessary.” - Robert Beal Blood transfusion has reached levels of safety that could not have been imagined a decade ago though…the relative calm could be perturbed again by an emerging pathogen with lethal potential, transfusion related Immuno-modulation and aged blood during prolonged storage. So, Dr Beal, we have a good but not perfect marriage, and we anticipate that continued counseling will further improve the relationship. Harvey JA, ASH 50th Ann Review; Blood 2008

  40. Thank you!

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