- 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
- need two doses 20min apart
- need platelets for rFVIIa to be effective
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
- DVT/ PE
- 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
- 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
- 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)
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.