Paper: Brill JB et al. Impact of Incorporating Whole Blood into Hemorrhagic Shock Resuscitation: Analysis of 1,377 Consecutive Trauma Patients Receiving Emergency-Release Uncrossmatched Blood Products. J Am Coll Surg 2022. PMID: 35290259
Clinical Question: In adult patients experiencing hemorrhagic shock, is whole blood transfusion associated with improved survival and/or decreased overall blood utilization compared to component therapy (RBCs, Plasma, Platelets)?
What They Did:
- Prospective, observational cohort study
- Injured adult patients receiving emergency-release blood products between Nov 2017 to Sept 2020
- Patients were evaluated in two groups
- Whole Blood (WB): Any group O whole blood units
- Cold-store low-titer (<1:256 Anti-A and Anti-B) non-leukoreduced, Rh D negative group O whole blood
- Due to increased demand for whole blood in June 2018 air transport transitioned to Rh D positive whole blood exclusively
- Child-bearing age females (<50 years) could not receive this product because of potential risk of hemolytic disease of the newborn
- All females <50 years requiring transfusion of emergency release blood received component therapy only (Rh D negative group O RBC, low anti-B titer group A plasma, and apheresis platelets)
- Some ground-transporting EMS services in the area continued to transfuse Rh D positive whole blood
- Component Blood (COMP): No whole blood; RBCs, Plasma, and Platelets
- Whole Blood (WB): Any group O whole blood units
- Univariate and multivariate analyses were performed (Due to large observed differences in regression model, post hoc adjustments with inverse probability, propensity scoring, and Poisson regression were performed to confirm results)
Outcomes:
- Co-Primary Outcome:
- Survival to discharge (Truncated at 30d if remaining hospitalized)
- 24-hour blood product use
- Secondary Outcomes:
- Transfusion reactions
- Acute renal failure
- Venous thromboembolic events
- Overall hospital-free days
- ICU-free days
- Ventilator-free days
- Blood product use by patient location
Inclusion:
- All level-1 adult trauma patients (≥16 years of age)
- Transported to Memorial Hermann Hospital
- Nov 2017 to Sept 2020
- Receiving emergency-release, uncrossmatched products in the prehospital or ED setting
Exclusion:
- None
Results:
- 1,377 patients receiving emergency release blood products
- WB: 840pts
- COMP: 537pts
- Injury Severity Score
- WB: 27
- COMP: 20
- Field Blood Pressure
- WB: 103mmHg
- COMP: 114mmHg
- Arrival Lactate
- WB: 4.2
- COMP: 3.5
- Univariate Analysis of Survival (Did not correct for multiple baseline differences between groups)
- WB: 75%
- COMP: 76%
- NO DIFFERENCE
- At 24 hours the component group received more platelets than the whole blood group
- Post arrival transfusions and complications (TRALI, TACO, and transfusion reactions) were rare and similar between groups (Except sepsis which was lower in the WB arm – 25 vs 30%)
- Multivariate Analysis of Survival (Corrected for age, male sex, injury severity, and prehospital systolic blood pressure)
- Logistic regression found WB independently associated with 4-fold increased survival: OR 4.10; p < 0.001
- The impact on survival remained regardless of location of transfusion, ISS, or presence of head injury
- WB patients also had a 60% reduction in overall transfusions: OR 0.38; 95% CI 0.21 to 0.70
- Logistic regression found WB independently associated with 4-fold increased survival: OR 4.10; p < 0.001
- Inverse Probability Adjustments, Propensity Scoring, & Poisson Regression
- Due to huge effect sizes and unbalanced baseline characteristics, further analyses had to be done to confirm the above results
- After adjustments whole blood remained associated with increased survival: OR 1.59; 95% CI 1.28 to 1.98; p <0.001
- After adjustments whole blood remained associated with decreased 24-hour transfusion volumes: RR 0.93; 95% CI 0.91 to 0.96; p <0.001
- Additionally whole blood associated with decreased hospital days but no differences in ventilator or ICU free days
Strengths:
- Large sample size with prospective data collection (This is better methodology than most previous evidence on this topic)
- No difference in age, race, ABO blood group or Rh D status at baseline between groups
- Groups received similar volumes of early blood transfusions (although more whole blood due to group assignment in the whole blood group) compared to component therapy group
- Multiple analyses done with various subgroups to confirm results
Limitations:
- Single center study may not generalize to other institutions
- Not a randomized or blinded trial which can introduce bias
- Unclear reasoning why some patients were selected to receive whole blood versus component therapy
- We don’t know what procedures were done or level of resuscitation that was performed on patients which could alter outcomes
- Most patients while arriving in shock, required fewer units than the original definition of MTP (Median of 6 total units transfused in first 24 hours in each cohort)
- The range of units transfused was rather wide but reflects the diverse population and severity of injury in this trial
- Including less severely injured patients could dilute the effect of on the primary outcomes (Higher odds ratios seen in the higher ISS groups)
- Transfusion of any amount of whole blood in any setting placed a patient in the whole blood arm, but most of these patients also received component therapy
- The ground EMS system that responds to the majority of traumas did not carry blood products during the study which creates a selection bias
- Groups were not balanced at baseline in terms of sex, injury severity score, field blood pressure, and arrival lactate (Whole blood group was sicker at baseline)
- WB group more likely to have sustained penetrating trauma mechanism, more severe anatomic injuries in the chest, abdomen, and extremities compared to component therapy group
Discussion:
- The resurgence of recent interest in whole blood stems from the military setting in austere environments where component therapy is unavailable owing to refrigeration, monitoring, transport, and other logistical barriers.
- Fully screened, appropriately collected and stored blood is now FDA approved in civilian trauma centers
- Cold-stored = 1 to 6 degrees Celsius
- Undergoing extensive pathogen testing
- Citrate phosphate dextrose adenine (CPBDA-1) prolongs shelf-live
- Maximum approved storage at 1 to 6 degrees Celsius is 35d for units using CPDA-1
- Massive Transfusion Protocol (MTP) vs Whole Blood
- The amount of saline solution, anti-coagulants, and other additives adds up to >1L after a single cooler of 6 RBC, 6 plasma, and apheresis platelet unit in component therapy
- Whole blood has a better hemostatic profile compared to component therapy on TEG
- Whole blood decreases exposure from ≥3 donors down to 1 donor exposure
- The use of low Anti-A/Anti-B titer group O whole blood as a universal product also eliminates the possibility of potential clerical and other crossmatching errors
- RCT of Whole Blood vs Component Therapy 2013 [2]
- Single-Center RCT of severely injured patients requiring large volume transfusions
- WB (1U) vs Component therapy (1U RBC + 1U plasma) on arrival to trauma center
- Both groups also received 1U platelets for every 6U whole blood or 6U RBC + 6U plasma
- Randomized 107 patients over 14 months
- No difference in mortality
- No decrease in transfusion requirement overall BUT decreased transfusion requirements in patients excluded with severe brain injury
- No differences in hemolysis, transfusion reactions (Similar safety)
- 2 Major issues
- Trial underpowered to demonstrate improved survival
- Platelets were removed due to IRB guidance
- Other than the above RCT most trials evaluating WB vs COMP therapy are limited due to small sample sizes and retrospective trial designs
- Given these limitations…
- Whole blood appears to have similar safety compared to component therapy in multiple trials
- Whole blood appears to have slightly better efficacy compared to component therapy in multiple trials
- Biggest Benefit
- Observed in patients with moderate to severe injury (ISS 16 to 39)
- Mildly injured patients (ISS <15) were going to have a strong probability of survival regardless of what they received
- Severely injured patients (ISS >40) were going to have a strong probability of death regardless of what they received
- Child-Bearing Age Females Excluded From Receiving Whole Blood
- This is due to the protocol change from mostly Rh D negative to mostly Rh D positive blood during the course of the study
- Potentially saving Rh D negative whole blood for this population alone may circumvent concerns about seroconversion in Rh D negative women
- Given these limitations…
Author Conclusion: “In patients experiencing hemorrhagic shock, WB transfusion is associated with both improved survival and decreased overall blood utilization.”
Clinical Take Home Point: Although this is not a randomized clinical trial and the presence of baseline differences exists between groups (Authors did account for many of these in their regression analyses), the imbalances would have favored the whole blood group doing worse (i.e. worse injury severity score, lower blood pressure, higher arrival lactate, more acute kidney injury, and more coagulopathic on TEG). Despite sicker patients the whole blood group did better, with less transfusions and not by a little bit. Obviously, we still need a well done RCTs to confirm these results (Without RCT data, it is impossible to say which is the superior approach), however many institutions have already changed practice to whole blood over component therapy.
References:
- Brill JB et al. Impact of Incorporating Whole Blood into Hemorrhagic Shock Resuscitation: Analysis of 1,377 Consecutive Trauma Patients Receiving Emergency-Release Uncrossmatched Blood Products. J Am Coll Surg 2022. PMID: 35290259
- Cotton BA et al. A Randomized Controlled Pilot Trial of Modified Whole Blood Versus Component Therapy in Severely Injured Patients Requiring large Volume Transfusions. Ann Surg 2013. PMID: 23979267
Post Peer Reviewed By Anand Swaminathan, MD (Twitter/X: @EMSwami)
