Factor VIIa

CLASS

• recombinant protein

MECHANISM OF ACTION

• tissue factor + VIIa + platelets -> platelet aggregation -> production of platelet-fibrin matrix -> haemostasis
• used in massive transfusion senario to attempt to control intractable haemorrhage

DOSE

• need two doses 20min apart
• expensive
• need platelets for rFVIIa to be effective

INDICATIONS

Consider rFVIIa when patient has had:

• 10 RBC
• 8U FFP
• 2U Plts
• 2U Cryoprecipitate
• warfarin has been reversed
• heparin has been reversed
• anti-fibrinolytic agents (tranexamic acid) have been considered
• requires T >35 C
• pH >7.2
• platelets > 100
• fibrinogen >1

-> rFVIIa 100mcg/kg, wait 20 min and repeat

ADVERSE EFFECTS

• DVT/ PE

EVIDENCE

• initially developed for haemophilia
• good theoretical basis
• encouraging case reports from use in trauma
• may avoid problems with ongoing transfusion – disease transmission, acute lung injury, TRALI, hypothermia, acid-base disturbance, volume overload
• probable publication bias -> tendency to publish cases where it has produced successful results
• massive transfusion and trauma -> off licence use

Mayer, S.A., et al (2005) “Recombinant Activated factor VII Intracerebral Haemorrhage Trial Investigators. Recombinant activated factor VII for acute intracerebral haemorrhage” N Engl J Med 352:777-785

• Multicentre RCT
• n = 399 with acute intracerebral haemorrhage
• single IV injection of recombinant factor VIIa (40, 80 or 160mcg/kg) VS placebo within 1 hour of their base line CT head scan.
  -> significant reduction in volume of haematoma on CT @ 24 hours with therapy proportional to dose.
  -> significant reduction in 30 day mortality without increase in severely disabled patients.
  -> no statistically significant increase in thromboembolic events although there was a trend.

Levi, M. et al (2010) “Safety of Recombinant Activated Factor VII in Randomized Clinical Trials” NEJM 363:79, pages 1791-800

• goal = evaluate the rate of thromboembolic risk in all published RCT’s using rFVIIA
• trials = 35
• n = 4468

Strengths

• arterial thromboembolic events: coronary, cerebral, other arterial events
• venous thromboembolic events:
  -> all well defined end-point with appropriate investigations.
• dose adjusted (< 80, 80-120, >120mcg/kg)
  -> similar ages and dose exposures

-> thromboembolic rate = 11.1%
-> significant increase in arterial thromboembolic rate (5.5% vs 3.2% with P < 0.05) -> likely to be coronary in origin.
-> no significant difference in venous thromboembolic rate
-> risk factors: > 65 years, higher dose, treatment for spontaneous CNS bleeding

AN APPROACH

• use in life threatening bleeding in trauma and massive transfusion
• use as per local protocols
• consider use in ICH
• vigilance regarding possible increase in thrombosis risk (especially coronary)