An evaluation of methods for producing low-titer group O whole blood to support military trauma resuscitation

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The US Armed Services Blood Program (ASBP) focuses on establishing a robust distribution system that ensures a viable supply of blood components in remote combat environments in order to enhance the survival of soldiers injured on the battlefield. However, it is difficult to deliver and subsequently maintain blood components at their appropriate temperatures in austere conditions. Since World War I, great strides have been made to safely transport packed red blood cells (PRBCs), fresh frozen plasma (FFP), and even cryoprecipitate (CRYO) as far forward as possible, but platelets (PLTs) require special handling—room temperature storage limits their use to 5 days because of the risk of causing a septic reaction. As a result, PLTs are generally not available at remote locations.1 Therefore, having the capability to collect and transfuse whole blood (WB) has supplemented the lack of PLT availability in austere locations.2
The concept of damage control resuscitation, transfusing PRBCs, FFP, and PLTs in balanced (1:1:1) ratios early in resuscitation, essentially attempts to recapitulate WB.3 The use of damage control resuscitation use has been proposed in recent publications dealing with military and civilian trauma patients.4–6 However, a 1:1:1 unit of reconstituted WB results in a product that has lower concentrations of red blood cells (RBCs), PLTs, and clotting factors compared with a WB unit that has not been fractionated. By contrast, a unit of WB contains approximately 500 mL and is only diluted by 70 mL of anticoagulant and preservative solution. As WB is typically not stored for as long as conventional RBC units before transfusion, an expectation is that any adverse effects of the RBC storage lesion on the recipient would be reduced by using a WB unit, although several recent randomized controlled trials have not found adverse effects from transfusing older RBC units in critically ill patients.5,7–11 Nevertheless, in casualties requiring massive transfusions (commonly defined as ≥10 units of RBCs within 24 hours), it is appropriate to consider a WB-based approach in the initial resuscitation effort in order to provide a balanced response to the massively bleeding patient; recent retrospective studies suggest that WB-based resuscitation is at least equivalent if not more effective than component-based therapy.4,12 Furthermore, WB represents a more logistically supportable option than component therapy for the provision of balanced transfusions in the prehospital and far-forward settings, as demonstrated by its successful use in World War II, the Korean War, and the Vietnam War.13
Despite the advantages of using WB for battlefield casualties, its use has been limited, particularly in the prehospital setting, by AABB Standard 5.14.1 that states that recipients shall receive ABO group–specific WB to eliminate the risk of acute hemolytic transfusion reactions (HTRs) caused by both the recipient’s and the donor’s naturally occurring anti-A and/or anti-B isohemagglutinins.14 Whole blood has the potential to cause a major, minor, or bidirectional incompatibility. A major incompatibility results from infusing an RBC unit that is incompatible with the recipient’s naturally occurring isohemagglutinins (e.g., a group A WB unit transfused to an O recipient). A minor incompatibility results from infusing plasma containing isohemagglutinins that are incompatible with the recipient’s RBCs or PLTs (e.g., a group O WB unit transfused to an A recipient). A bidirectional incompatibility occurs when both a major mismatch and a minor mismatch are present (e.g., a group A WB unit transfused to a group B recipient). Because WB contains both RBCs and plasma, the compatibility of both components with the recipient must be considered.
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