WHOLE BLOOD

Whole blood delivers all the components of blood in the same ratio in which they were lost; WB is independently associated with improved survival.21-23 In deployed environments, the logistical challenges of maintaining a supply of blood components has led to the use of WB collected onsite from “walking blood banks,” especially to provide platelets for hemostatic resuscitation. Depending where the blood products have been collected, some of the whole blood products in the deployed setting (platelets or WB) are not prospectively tested for Transfusion-Transmitted Diseases (TTDs). Rapid TTD test kit use is encouraged to screen for HIV, Hepatitis B and C, and malaria or other diseases for which kits are available. Recipients of these blood products must be tested at 3, 6 and 12 months post-transfusion to monitor for disease transmission.

Type-Specific Whole Blood (TSWB), often referred to as Fresh Whole Blood (FWB), is collected from donors in the deployed setting and must be an ABO match with the recipient. The availability of TSWB may be limited due the constrained pool of donors who must be tested for TTDs and blood group compatibility with recipients. In addition, the chaotic conditions of mass casualty scenarios complicate the matching of blood types between donors and recipients, increasing the risk of clerical errors causing hemolytic transfusion reactions.

In order to improve the availability and safety of WB, low anti-A and anti-B titer (<256 by tube method, though the definition of ‘low titer’ can vary by medical agency or facility) group O blood has been identified as a practical, effective universal blood product for resuscitation of exsanguinating hemorrhage.24,25 Like all blood donors, “O low titer” donors should be tested for TTDs and undergo confirmatory typing and an antibody screen (type and screen) in addition to testing for anti-A and anti-B antibodies. LTOWB can be collected from pre-screened walking blood banks in the deployed setting or collected in Armed Services Blood Program donor centers and stored refrigerated for 21 days in CPD or 35 days in CPDA-1.26 It is important to note that LTOWB has been used safely in the military setting since WW1, with hundreds of thousands of units transfused and only one recorded hemolytic reaction, due to a clerical error.27

In 2014 the U.S. Army Rangers developed and instituted the Ranger O Low titer blood (ROLO) program. Low Titer Rangers were identified as a screened donor pool serving as an immediate WBB capability (approximately 2/3 of the group O Ranger population is naturally low titer, generally accepted as having anti-A and anti-B levels less than 1:256 concentration). Every Ranger is trained in how to set up and administer a Fresh Whole Blood buddy transfusion. This program represents a success story of leadership and since 2015 every Ranger task force has deployed with a functional ROLO program. This model is currently being broadened to other prehospital communities.

Available data suggest that Cold-Stored WB (CWB) will provide robust platelet hemostatic function during the first 2 weeks of storage. When using anticoagulants and preservatives such as CPD and CPD-A, function is moderately reduced during the remaining shelf life (21 days for Citrate Phosphate Dextrose (CPD) WB and 35 days for Citrate Phosphate Dextrose Adenine (CPDA-1) WB), but it should be noted that some platelet function remains and that WB plasma hemostatic function is comparable to that of liquid plasma. Throughout its shelf life, CWB remains a relatively hemostatic product compared to RBCs and plasma alone28-30 Patients receiving MT with CWB stored for more than 2 weeks may require additional support with platelet transfusions or FWB (consider a ratio of 3:1 of CWB: FWB as available). Similarly, CWB that has been leukoreduced with a filter that does not spare platelets and that contains fewer or effectively no platelets requires supplementation with platelet or FWB transfusion.31 Cold-stored LTOWB and TSWB have been used successfully and safely to treat trauma and other causes of massive hemorrhage, such as obstetric emergencies and bleeding in cardiac surgery, in leading U.S. civilian hospitals.30 ,32-40

WB is standard practice for resuscitation of combat casualties. For guidance regarding use of FWB, see the Joint Trauma System (JTS) CPG entitled Fresh Whole Blood Transfusion.41

RED BLOOD CELLS

RBC units may be stored for up to 42 days under refrigeration when stored in additive solution (e.g., AS-5) or 35 days if stored in CPDA1. In addition, “frozen” RBCs (stored frozen with glycerol cryoprotectant for up to 10 years at <-65°C, then thawed and rinsed in an automated process prior to transfusion) are used interchangeably and successfully with standard RBC units when needed, although these units require at least an hour and a half and specialized equipment to prepare. Transfusion of thawed fRBC units without removal of glycerol is absolutely contraindicated and is lethal to the recipient. Thawed and deglycerolized RBCs can be stored for 14 days with refrigeration. For guidance regarding use of fRBCs see the JTS CPG entitled Frozen and Deglycerolized Red Blood Cells.42

PLASMA

Plasma can be stored frozen and then thawed on-demand (FFP), or pre-thawed and stored refrigerated for up to 5 days (so-called “thawed plasma”). The delay in treatment imposed by slow thawing of FFP (up to 30 minutes or more) has necessitated the widespread maintenance of thawed plasma inventories for immediate, emergency use. This typically results in significant waste due to the 5-day post-thaw shelf life. Plasma can also be supplied as “liquid” (never frozen) plasma and stored for 26 days in CPD anticoagulant solution, or 40 days in CPDA-1. Available data suggest that “thawed” and “liquid” plasma may be functionally interchangeable in most trauma patients. Note that no randomized trials have compared these products and the data regarding the hemostatic capacity of liquid plasma stored beyond 28 days are very limited.42,43 Although group AB plasma is classically considered the universal donor, it is now widely recognized that A plasma can, in fact, be considered universal since group A individuals do not generally make high titer anti-B antibodies and B red cells express the B antigen at low density, thus making them much less susceptible to hemolysis than A red cells.

Freeze-Dried Plasma (FDP) was used by U.S. Forces during World War II and has been in use by the French military since the 1940s. French military FDP is available to U.S. Special Operations Forces under an Emergency Use Authorization from the Food and Drug Administration (FDA).24 FDP is considered functionally interchangeable with other plasma products for trauma resuscitation. FDP or Spray-Dried Plasma (SDP) may become more broadly available to U.S. Forces in the near future.44-45

PLATELETS

In contrast to red cells and plasma, platelets collected in theater by apheresis traditionally have been stored at room temperature (20-24°C), under constant agitation, for a maximum of 5 days with an extension to 7 days total if shipped to another facility. These storage conditions are optimized to extend in vivo platelet circulation, but not hemostatic function, safety, or availability.46 Platelets are vital for hemostasis and their early use in a balanced transfusion strategy is associated with increased survival in trauma.16,19,47,48 Platelets stored under refrigeration (1-6°C), or “Cold-Stored Platelets” (CSP), maintained without agitation for up to 3 days in plasma, have long been approved by the FDA for treatment of bleeding patients. Refrigerated storage better preserves platelet hemostatic function and clearly reduces the risk of bacterial growth, the major hazard of transfusing room temperature-stored platelets.49,50 CSP have been proven effective in clinical trials and used successfully in combat trauma patients in the U.S. Central Command area of operations.53 Cold-stored platelets in platelet additive solution (CSP-PAS) or plasma retain function for at least 15 days and are compatible with blood warmers and rapid infusers. 51 CSP can be collected in theater and used interchangeably with other platelet products.52

Fibrinogen concentrate has not been studied adequately in trauma patients either, but several factors suggest that it may be helpful. These include: 1) fibrinogen is the fundamental substrate of clot formation; 2) fibrinogen is rapidly consumed in trauma; and 3) cryoprecipitate, a less purified source of fibrinogen, has been shown to be an essential component of MT protocols for mitigating the dilutional coagulopathy caused by red cell additive solution and anticoagulant.17,53-56

Prothrombin Complex Concentrates (PCCs) are only indicated for patients requiring urgent warfarin reversal and have not been adequately studied in a broad trauma population. PCCs could be considered if: 1) the patient is anticoagulated; or 2) there is clear evidence of delayed initiation of clot formation refractory to platelets, fibrinogen or cryoprecipitate and TXA (e.g., prolonged thrombelastography rapid time [TEG-R] or rotational thromboelastometry clotting time [ROTEM CT]). PCCs should not be routinely used in trauma outside the context of a clinical trial as they may cause harm due to excessive thrombogenicity.57