One thing is clear from the military and civilian literature – hemorrhage kills1,2. Overall, 40-50,000 deaths per year in the US are preventable with appropriate hemorrhage control and resuscitation. The demographic of these victims is primarily young, healthy individuals who would otherwise have had the chance to live a productive life.
Resuscitation should address the components responsible for hemorrhagic shock – blood loss and systemic injury – while mitigating hemodilution. There has been a concerted push away from using clear fluids for initial resuscitation, with recent evidence pointing to the mortality benefit of using balanced ratios of packed red cells, plasma, and platelets in massive transfusion3.
The aim of balancing components is to approximate reconstituted whole blood – so why not just give whole blood?
Let’s compare what you get with these two modalities4. Giving a unit each of PRBC, FFP, platelets, and cryoprecipitate provides a hematocrit of 29%, coagulation factors about 65% of normal, 80,000 platelets, and 1g of fibrinogen – all with a significant load of citrate and amounting to a volume of almost 700mL. 500mL (1 unit) of fresh whole blood, on the other hand, has a hematocrit of 38-50%, coagulation factors at 100%, platelets at a normal range, 1g fibrinogen, and much lower amounts of citrate. To get the equivalent amount from component therapy would require twice the volume (and twice the citrate) of components. The citrate, while useful as a preservative, binds calcium, something that is critical for both hemostasis and cardiac function in these already tenuous patients.
As the title suggests, whole blood is not new – it was utilized as early as the 1800s and then in both World Wars as
well as the Korean and Vietnam wars5. By the 1980s, component therapy had however become the norm, only for medicine to return to the whole blood concept by the 2000s. Our knowledge on its modern use is driven primarily by the military.
Repine described the importance of revisiting fresh whole blood during the Iraq conflict, citing a potential benefit in addressing the coagulopathy of trauma6. Spinella and colleagues compared fresh whole blood to component therapy in this 2009 paper, showing significantly improved 24-hour and 30-day mortality in the whole blood group7. The overall volume and importantly the amount of citrate was much lower in the patients receiving whole blood. Guidance has been published on military implementation of fresh whole blood, and its use has now become part of Tactical Combat Casualty Care training8,9.
As with many things in medicine, giving whole blood has challenges. Unlike component therapy, whole blood has both cellular and antibody components, making ABO compatibility very challenging. One obvious solution to this challenge is to transfuse only type-specific blood. In the military setting, where patient blood types can be readily obtained, and where “walking blood banks” of healthy volunteers can feasibly be assembled in a short time period, type-specific whole blood can be rapidly collected and transfused.
In civilian practice, this approach is impractical. Our civilian trauma patients do not carry immediate identification of their blood type – waiting for blood type results before giving a transfusion would worsen hemorrhagic shock. Plasma antibody levels have been shown to vary significantly from donor to donor. Thus, it has been possible to select type O whole blood units with very low levels of anti-A and anti-B antibodies. This has reduced the risk of hemolysis for incompatible recipients. The typical unit will thus be type O, low titer, and leukoreduced. Male donors are typically chosen to reduce the risk of transfusion-related acute lung injury (TRALI).10, 11
Civilian use also mandates storage as scores of ready donors are not generally available. Storage times in civilian practice have varied from 5-15 days, though a recent statement from AABB allows storage for up to 21 days. Storage may however come at the cost of hemostatic function – there is evolving evidence that, when using viscoelastic assays, platelet function in particular reduces over the storage period12.
But is whole blood any good in civilian practice? In a single-center RCT, Cotton and colleagues randomized 107 patients to either leukoreduced modified whole blood or component therapy13. Although they did not show a mortality difference at 24 hours or 30 days, they did highlight that product use in the whole blood group was lower at 24 hours. Whilst ambitious, this trial had limitations: low numbers, exclusion of TBI patients, single-center. Also, at the time, the leukoreduction process removed platelets which may have affected outcomes – current leukoreduction filters are platelet sparing. Finally, they excluded patients who could not wait the 5-10 minutes to obtain a rapid blood typing, possibly thus excluding the very patient group in whom whole blood may have made the most difference.
More recently, Yazer’s group published their single-center trial demonstrating a change in practice at their civilian level 1 trauma center14. Up to two units of leukoreduced (but platelet sparing) group O whole blood were administered to 47 adult male trauma patients with ABC score ³2, and compared to similar patients enrolled in their data bank in the preceding two years who had received component therapy.
No adverse reactions occurred, though the ultimate benefit in reducing total transfusion products could not be determined due to small numbers.
Adverse events are always a concern. A recent review of transfusion practice has shown overall low rates of complications (including disease transmission, immune-mediated complications, and volume overload)15. US military experience of over 10,000 units of fresh whole blood transfusions to date have had only one reported case each of graft-versus-host disease and transmission of hepatitis C virus and HTLV. The Spinella paper showed a higher rate of renal failure and ARDS in the whole blood group – albeit this group did not use leukoreduced product, which may have contributed an inflammatory component.
For the last year at our hospital, we have incorporated a whole blood program. We hold 4 units of low-titer type O whole blood in our trauma bay – these can be stored for up to 15 days before being replaced. Another 2 units are immediately available from the blood bank. Our triggers for transfusion are similar to other US level 1 centers who use whole blood: adult males (>18 years) or adult females (>age 50 years) who have an ABC score ³2. We exclude patients who arrive in arrest or who have clear signs of a severe traumatic brain injury. Thus far, our survival figures have approached other published reports (approximately 79%) with only one instance of transfusion-associated circulatory overload (TACO), and no hemolytic reactions.
Developing a whole blood program is dependent therefore on many factors: the logistical aspects include not only a protocol for collection, storage, and transfusion, but a ready means to offer definitive bleeding control16. Practical experience from local area hospitals that have successfully implemented whole blood programs highlight the importance of institutional buy-in – this includes physicians, nurses, and allied staff in emergency medicine, surgery, and hematology/blood bank. Keeping the indications simple assists point-of-care decision making. Given the relative novelty of using this in the civilian setting, all those involved in the care of the trauma patient should be up-to-date with the evidence.
This evidence, of course, needs to further develop. The Linking Investigations in Trauma and Emergency Services (LiTES) group is currently undertaking a US-based observational study on the use of whole blood in the severely injured patient17. Recently, London’s Air Ambulance announced a trial of administering whole blood in the prehospital setting18.
So, what is old becomes new again – a modality used regularly in major world wars is showing benefit again in modern military trauma management. Time will tell how and where this fits into the management of the severely injured civilian trauma patient.
Thank you to my colleagues Drs. Jeremy Cannon and Joshua Hazelton for their assistance in putting together this blog post.
- Eastridge B, Hardin M, Cantrell J et al. Died of wounds on the battlefield: Causation and implications for improving combat casualty care. J Trauma Acute Care Surg July 2011 doi: 1097/TA.0b013e318221147b
- A National Trauma Care System: Integrating Military and Civilian Trauma Systems to Achieve Zero Preventable Deaths after Injury. The National Academies of Sciences, Engineering, and Medicine. Published June 2016, Accessed October 24, 2018. http://www.nationalacademies.org/hmd/Reports/2016/A-National-Trauma-Care-System-Integrating-Military-and-Civilian-Trauma-Systems.aspx
- Holcomb JB, Tilley BC, Baranuik S et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with sever trauma. JAMA February 2015 doi: 1001/jama.2015.12
- Armand R, Hess JR. Treating coagulopathy in trauma patients. Transfusion Medicine Reviews July 2003 https://www.ncbi.nlm.nih.gov/pubmed/12881783
- AABB Highlights of Transfusion Medicine History http://www.aabb.org/tm/Pages/highlights.aspx Accessed October 24, 2018
- Repine TB, Perkins JG, Kauvar DS, Blackborne L. The use of fresh whole blood in massive transfusion. J Trauma June 2006 doi: 1097/01.ta.0000219013.64168.b2
- Spinella PC, Perkins JG, Grathwohl KW et al. Warm fresh whole blood is independently associated with improved survival for patients with combat-related traumatic injuries. J Trauma April 2009 doi: 1097/TA.0b013e31819d85fb
- Strandenes G, De Pasquale M, Cap AP, et al. Emergency whole-blood use in the field: a simplified protocol for collection and transfusion. Shock May 2014 doi: 1097/SHK.0000000000000114
- Reisberg J, Cap A. Fresh Whole Blood Transfusion “FAQs” in Prolonged Field Care. December 2014. http://www.specialoperationsmedicine.org/Documents/PFC%20WG/Fresh%20Whole%20Blood%20(FWB)%20Transfusion%20FAQ%27s%20(December,%202014).pdf Accessed October 24, 2018
- Belin TR, Yazer MH, Meledeo MA et al. An evaluation of methods for producing low-titer group O whole blood to support military trauma resuscitation. J Trauma Acute Care Surg June 2017 doi: 1097/TA.0000000000001437
- Petraszko T. Transfusion-related acute lung injury (TRALI). Canadian Blood Services Professional Education. https://professionaleducation.blood.ca/en/transfusion/publications/transfusion-related-acute-lung-injury-trali Accessed October 24, 2018
- Remy KE, Yazer MH, Saini A et al. Effects of platelet-sparing leukocyte reduction and agitation methods on in vitro measures of hemostatic function of cold-stored whole blood. J Trauma Acute Care Surg doi: 1097/TA.0000000000001870
- Cotton BA, Podbielski J, Camp E et al. A randomized controlled pilot trial of modified whole blood versus component therapy in severely injured patients requiring large volume transfusions. Ann Surg October 2013 doi: 1097/SLA.0b013e3182a4ffa0
- Yazer MH, Jackson B, Sperry JL et al. Initial safety and feasibility of cold-stored uncrossmatched whole blood transfusion in civilian trauma patients. J Trauma Acute Care Surg July 2016 doi: 1097/TA.0000000000001100
- Carson JL, Triulzi DJ, Ness PM. Indications for and adverse effects of red-cell transfusion. N Engl J Med September 2017 doi: 1056/NEJMra1612789
- Stubbs JR, Zielinski MD, Jenkins D. The state of the science of whole blood: lessons learned at Mayo Clinic. Transfusion April 2016 doi: 1111/trf.13501
- Linking Investigations in Trauma and Emergency Services Task Orders https://www.litesnetwork.org/about/task-orders/ Accessed October 24, 2018
- News – London’s Air Ambulance. https://londonsairambulance.co.uk/our-service/news/2018/10/landmark-study-to-save-hundreds-more-lives Published October 25, 2018. Accessed October 26, 2018