All The Blood?

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Whole blood transfusions have been used in the management of hemorrhagic shock since World War I, with several peaks and troughs in the frequency of its use noted throughout the last century.

Since the early 2010s, use of whole blood (WB) transfusion in the management of hemorrhagic shock has seen a resurgence.

While there are experts swearing by whole blood transfusions and their medical and logistical benefits, others point to a lack of randomized controlled trials (RCT) demonstrating a mortality benefit with WB compared to blood component therapy.

This week, we are looking at one of the largest multi-center prospective observational trials on the efficacy of WB transfusions in patients with haemorrhagic shock.

The study, titled “Whole Blood Resuscitation and Association with Survival in Injured Patients with an Elevated Probability of Mortality”, by Sperry et al, is a prospective, multicenter, observational cohort study enrolling patients from seven different level I trauma centers in the United States.

The main aim of the study was to assess the safety and efficacy of low-titer group O positive whole blood (LTOWB) in patients with hemorrhagic shock compared to blood component therapy.

Patients were included in the study if they met the at least two of the Assessment of Blood Consumption (ABC) criteria for risk of massive transfusion, which include hypotension (SBP ≤ 90 mmHg), penetrating injury, a positive FAST exam, heart rate ≥ 120/min, and if they required both blood transfusion therapy and hemorrhage control procedures in the operating room within 60 minutes of arrival.

The primary outcome was 4-hour mortality, while secondary outcomes included 24-hour mortality, 28-day mortality, achievement of hemostasis, adjudicated death from exsanguination/hemorrhage. Additional safety outcomes, such as the incidence of nosocomial infections, multiple organ dysfunction and thromboembolic events were also prespecified and assessed during the study.

A total of 1051 patients meeting the inclusion criteria were enrolled in the study during a 42 month enrollment period. Based on the treatment received, patients were divided into the whole blood group (624 patients) and blood component therapy (BCT) group (427 patients).

There were no statistically significant differences between groups regarding median patient age (35 vs 35 years), Injury Severity Score (22 for WB vs 21 for BCT), incidence of blunt vs penetrating injury mechanisms, shock index (1.06 vs 1.00) or the incidence of having received prehospital blood products or crystalloid infusions.

Patients in the whole blood group were somewhat sicker, with significantly lower median Glasgow Coma Scale values (14 vs 15), SBP (99 mmHg vs 105 mmHg) and a significantly higher rate of traumatic brain injury (15.9% vs 10.3%).

Regarding the primary outcome, there was no statistically significant difference in unadjusted 4-hour mortality between groups (8.2% for WB vs 7.5% for BCT, p = 0.70). The same was observed for both 24-hour and 28-day mortality (13.4% vs 11.5%; 17.9% vs 15.5%, p > 0.05 for both).

Regarding secondary outcomes, there was no significant difference between groups for mortality due to adjudicated death from exsanguination, rate of achieving hemostasis or the incidence of any of the safety outcomes.

Interestingly, the authors performed another analysis, determining a prehospital predicted risk of 28-day mortality for each individual patient based on prehospital vital signs, prehospital interventions/procedures, and injury severity characteristics and then stratifying them into groups. Patients with a calculated probability of mortality >50% had a significantly lower 28-day mortality rate if they received WB compared to BCT (39.3% vs 72.5%, p < 0.01).

Upon further analysis, the authors found that patients with a prehospital predicted risk of mortality >10% had significantly lower 4-hour and 24-hour mortality rates if they received whole blood, while patients with a prehospital predicted risk of mortality >20% had a significantly lower 28-day mortality rate if they received whole blood, compared to BCT.  

The inclusion of an analysis which takes into account the prehospital risk of mortality may be seen as “leveling the playing field” and “adjusting for confounders”,  seeing that patients in the WB group were both sicker and had significantly higher rates of TBI.

However, the fact that the authors used a model for mortality risk prediction not validated elsewhere may somewhat diminish the enthusiasm around these results.

In summary, the finding that patients receiving whole blood transfusions had both greater and more significant benefits in mortality, both short- and long-term, the sicker they were, is an exciting prospect for future studies, including several RCTs on the efficacy and safety of WB currently being conducted.

That’s it for this week, stay safe and keep reading.


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