Massive Blood Transfusion
- Jan 14th, 2014
- Zach Radwine
Resuscitation with crystalloid and plasma-poor red blood cell concentrates can lead to dilutional coagulopathy, which is further exacerbated by hypothermia, acidosis, and massive tissue injury that accompany trauma and large-volume resuscitation.
Since the shift from whole blood to blood components in the 1980s there has been ongoing controversy regarding the ratio of components that should be given during massive transfusion (MT) in order to treat/prevent this coagulopathy. Recent evidence has suggested, largely in military setting, that a 1:1:1 ratio should be the goal.
Here we examine the evidence for the optimal ratio of plasma to platelets to red blood cells in massive transfusion.
- Classic definition of MT: >10 units PRBC in 24 hours
- Newer definition: 5 units PRBC in 3 hours
- 1 unit = about 200ml PRBC, will raise hct by 3-4% unless bleeding is ongoing
- Coags should be monitored with PT, PTT, and platelets, preferably after every 5 units PRBC
- Replace FFP for PT/PTT > 1.5x control
- Replace platelets for < 50,000
- Trauma patients with coagulopathy have 3-4x greater mortality
- Reasons for coagulopathy
- Intrinsic: Acidosis, hypothermia (< 35 degrees C), widespread tissue injury, consumption of coagulation proteins, fibrinolysis
- Induced: Dilution of clotting factors and platelets w/ PRBC and crystalloid
- Other complications
- Blood is anti-coagulated w/ citrate which can cause metabolic alkalosis and hypocalcemia
- Hypothermia (use blood warmer)
- Hyperkalemia (only occurs w/ long-stored red cells transfused at high volumes into the central circulation)
What’s New: Review of Recent Literature
- Rajasekhar 20111
- Systematic review of 11 observation studies
- Majority of studies: Higher FFP/PRBC ratios associated w/ survival benefit, but subject to biases:
- Survival bias: Patients who die shortly after enrollment receive less FFP than those who survive longer
- Decreased crystalloid: It has been suggested that increased crystalloid use is associated w/ worse outcomes, therefore the role of decreased crystalloid use in the setting of increased blood product transfusion is unclear
- Shaz 20102
- Retro/prospective review of 214 civilian pts showed improved 30-day mortality with increased ratios of plasma, platelets, and cryoprecipitate.
- Perkins 20093
- Retrospective review of 694 military pts showed that ratio ≥ 1:8 apheresis platelets:PRBC associated w/ improved survival at 24 hours and 30 days.
- Phan 20094
- Systematic review: 11 retrospective studies (1 military)
- Seven showed improvement w/ incr FFP/PRBC ratio
- One showed optimal ratio between 1:2 and 1:3
- One showed no benefit > 1:3
- One showed no effect on mortality
- One showed that when treated as a time-dependent covariate, plasma ratio has no survival advantage suggesting that rather than high plasma ratios causing improved survival, in fact patients who survive longer are able to receive higher volumes of plasma
- Zehtabchi 20095
- Three retrospective reviews and 1 prospective cohort provide inadequate evidence to support or refute the use of high FFP:PRBC ratio in pts w/ severe trauma.
- Holcomb 20086
- Retrospective review 466 pts compared FFP/PRBC < 1:2 and ≥ 1:2
- Also compared high to low ratio platelets
- High ratio FFP and platelets associated with improved survival
- Conclusion: to statistically ensure 98% of pts receive at least 1:2 FFP/PRBC, guideline should be 1:1
- Truncal hemorrhage was cause of death in 10% of high ratio and 44% in low ratio
- 17% of pts received rfVII
- Borgman 20077
- 246 military pts, compared FFP/PRBC 1:8, 1:2.5, 1:1.4
- Conclusion: mortality improved w/ incr in FFP/PRBC ratio
- Sig number of pts received rfVII and fresh whole blood
- rfVII in high vs low plasma: 38 vs 16%
- Severe (AIS scores 4 or 5) thoracic injuries were more common in the low ratio group compared to med and high
- Median time to death in low plasma = 2h, med = 4h, high = 38h
Bottom Line/Pearls & Pitfalls
A 1:1:1 ratio of FFP to platelets to red blood cells during massive transfusion has been shown in observational studies to offer a mortality benefit. However, there is not uniform agreement in the literature, there have been no randomized controlled trials on this subject, the existing studies are subject to significant biases, and the extent of risk associated with higher volume of FFP/platelets including volume overload, transfusion reactions, transmission of infectious organisms, TRALI, MOF, thromboembolic events, and cost/availability of FFP/platelets has not been well-characterized.
Discussion Questions/Future Exploration
- What is the optimum ratio of blood products to administer during massive transfusion?
- What is the optimum timing for giving the products (i.e. 6 units PRBC followed by 6 units FFP is likely not equivalent to alternating each product or giving simultaneously)?
- Is there a utility of real-time coagulation measurements such as TEG in massive transfusion?