Massive Blood Transfusion

Background

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.

Recap Basics

  • 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
  • However:
    • 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.

Further Reading

  1. Rajasekhar A, et al. Survival of trauma patients after massive red blood cell transfusion using a high or low red blood cell to plasma transfusion ratio. Critical Care Medicine. 39(6) June 2011 pp 1507-1513.
  2. Shaz BH, et al. Increased number of coagulation products in relationship to red blood cell products transfused improves mortality in trauma patients. Transfusion. 2010 Feb;50(2):493-500.
  3. Perkins JG, et al. An Evaluation of the Impact of Apheresis Platelets Used in the Setting of Massively Transfused Trauma Patients. The Journal of Trauma: Injury, Infection, and Critical Care 66(4) April 2009 pp S77-S85.
  4. Phan HH, Wisner DH. Should we increase the ratio of plasma/platelets to red blood cells in massive transfusion: what is the evidence? Vox Sanguinis. Apr2010 Part 2, Vol. 98 Issue 3p2, p395-402.
  5. Zehtabchi S, Nishijima D. Impact of transfusion of fresh-frozen plasma and packed red blood cells in a 1:1 ratio on survival of emergency department patients with severe trauma. Acad Emerg Med May 2009 Vol 16 No 5. pp 371-77.
  6. Holcomb JB, et al. Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Ann Surg. 2008 Sep;248(3):447-58.
  7. Borgman M, et al. The Ratio of Blood Products Transfused Affects Mortality in Patients Receiving Massive Transfusions at a Combat Support Hospital. The Journal of Trauma, Infection, and Critical Care 63(4) October 2007 pp 805-813.
  8. Rainer TH, et al. Early risk stratification of patients with major trauma requiring massive blood transfusion. Resuscitation 2011 Jun;82(6):724-9.
  9. Fuller G, et al. Recent massive blood transfusion practice in England and Wales: view from a trauma registry. Emerg Med J. 2012 Feb;29(2):118-23.

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?
Edited by Alex Koyfman

7 thoughts on “Massive Blood Transfusion”

  1. Nice summary, Dr. Radwine!

    Just a couple tidbits I’d like to add in:

    1) Usually volume of PRBC is typically closer to 300mL (250-300 usually).
    2) It has been suggested that platelets should be considered near 100K in neurosurg patients (albeit without any fantastic evidence)

    As for your discussion questions…

    One large study (nearing completion) to be on the lookout for that will likely shed light on our optimal ratio quandaries is the PROPPR trial. http://cetir-tmc.org/research/proppr

    As for timing, I’d personally say the earlier the better…….in patients who need it. Sadly, you and I both know this is easier said than done. I think the real issue is accurately IDENTIFYING the patients in need for MTP activation, which brings me to the next question…

    I think TEG/ROTEM (maybe sonoclot?) has a HUGE role in the management of traumatic coagulopathy. A great paper on this can be found here:
    http://journals.lww.com/jtrauma/Citation/2013/06000/Practical_application_of_point_of_care_coagulation.31.aspx

    Finally, if you’re interested in trauma/hemostasis, I have a collection of my personal notes free online here → http://hurtregistry.org/notes/

    Thanks! Keep up the good work!
    -Derek

  2. Nice summary, Dr. Radwine!

    Just a couple tidbits I’d like to add in:

    1) Usually volume of PRBC is typically closer to 300mL (250-300 usually).
    2) It has been suggested that platelets should be considered near 100K in neurosurg patients (albeit without any fantastic evidence)

    As for your discussion questions…

    One large study (nearing completion) to be on the lookout for that will likely shed light on our optimal ratio quandaries is the PROPPR trial. http://cetir-tmc.org/research/proppr

    As for timing, I’d personally say the earlier the better…….in patients who need it. Sadly, you and I both know this is easier said than done. I think the real issue is accurately IDENTIFYING the patients in need for MTP activation, which brings me to the next question…

    I think TEG/ROTEM (maybe sonoclot?) has a HUGE role in the management of traumatic coagulopathy. A great paper on this can be found here:
    http://journals.lww.com/jtrauma/Citation/2013/06000/Practical_application_of_point_of_care_coagulation.31.aspx

    Finally, if you’re interested in trauma/hemostasis, I have a collection of my personal notes free online here → http://hurtregistry.org/notes/

    Thanks! Keep up the good work!
    -Derek

  3. Agree with Derek. Gets tricky when trying to do early identification of pts who needs MTP. Fine balance between amount of time spent in the ED performing adequate resuscitation with fluids/blood products and time to correction of surgical causes of bleeding. The Damage Control Resuscitation literature seems to point towards 1) stabilizing BP, 2) minimizing saline/LR, 3) preventing the deadly triad and 4) getting patient to OR ASAP.

    My impression from reading about MTP is that the 1:1:1 ratio is difficult to achieve.

  4. Agree with Derek. Gets tricky when trying to do early identification of pts who needs MTP. Fine balance between amount of time spent in the ED performing adequate resuscitation with fluids/blood products and time to correction of surgical causes of bleeding. The Damage Control Resuscitation literature seems to point towards 1) stabilizing BP, 2) minimizing saline/LR, 3) preventing the deadly triad and 4) getting patient to OR ASAP.

    My impression from reading about MTP is that the 1:1:1 ratio is difficult to achieve.

  5. Thanks Derek for posting your personal notes online for free! Looks great. Question for anyone…where does tranexamic acid fit in your institutional massive transfusion protocol?

Leave a Reply

Your email address will not be published. Required fields are marked *