An international survey on the use of low titer group O whole blood for the resuscitation of civilian trauma patients in 2020

There is increasing military and civilian evidence demonstrating that early intervention with blood products in patients with traumatic bleeding saves lives.1-4 One component that provides balanced resuscitation is whole blood (WB). When it is provided to a recipient whose ABO group is unknown, such as in the pre-hospital phase of resuscitation or early in the patient's in-hospital course, it must be group O to avoid immediate hemolytic reactions, and the plasma must contain levels anti-A and -B that are below the institute's maximum titer threshold.5 Units fulfilling these criteria are known as low titer group O WB (LTOWB), and its use is increasing. A survey conducted in 2018 revealed 15 hospital systems in the USA and a hospital in Norway that were using LTOWB, primarily for the resuscitation of trauma patients.6 The survey was repeated in 2019 and the number of respondents from the USA increased to 24.7 The 2019 iteration of the survey included two international air ambulance services that transfuse LTOWB in the pre-hospital setting in Israel and the United Kingdom. To appreciate the number of hospitals and emergency providers that are currently using LTOWB, and the scope of their practice vis-à-vis LTOWB, the THOR (Trauma, Hemostasis & Oxygenation Research network)/AABB working party conducted another survey of the known American and international services that are either currently using LTOWB or are in the advanced planning stages of implementing an LTOWB program as a guide for other hospitals that are considering implementing a similar program (Table 1). Amongst the 37 respondents (Table 2), there were nine hospitals that did not have a limit on the number of LTOWB units that could be administered to traumatically injured patients, although at four of these hospitals there was a requirement for the blood bank physician to communicate with the trauma team about the patient's ongoing blood needs at some point during the resuscitation. Seven of these nine centers provided the number of LTOWB units in their hospital's inventory, and the average was 17 with a standard deviation (SD) of 7 units. Note that the 31st edition of the AABB Standards, Standard 5.27.1.1, requires each transfusing center to have a policy that dictates the maximum number of LTOWB units that a patient can receive; an institute's policy of having no maximum number of units would satisfy this Standard as long as the policy is codified in writing. At the remaining 28 sites that have a limit on the number of LTOWB units per patient, the average number of units that could be administered per patient was 4 units with an SD of 2 and a range of 2-8 units. The maximum number of LTOWB units at the pre-hospital providers in this survey (Magen David Adom in Israel, and Barts Health NHS Trust/London air ambulance; two and four units, respectively) were not included in this average as it is expected that the number of LTOWB units transported in a rescue vehicle would be fewer than those available in a hospital. Interestingly, 8 out of 37 (22%) of the respondents indicated that LTOWB could be administered to both trauma and non-trauma patients who are massively bleeding, while 2 out of 37 (5%) respondents indicated that LTOWB could be used for both trauma and selected non-trauma massive bleeding patients whose bleeding etiologies included bleeding in the operating room. The remaining 27 out of 37 (73%) respondents indicated that LTOWB was only administered to trauma patients. Consistent with previous surveys, more than half of the respondents (23 out of 37, 62%) use leukoreduced LTOWB. The most common definition of low titer anti-A and -B continued to be <200 followed by <50. The hospital in Norway uses two requirements to qualify a low titer unit: IgM titer <250 and IgG titer <500 (listed as "Other" for Question 6 in Table 1). Of the 29 respondents who indicated the method by which the anti-A and -B titers were performed on their LTOWB units, the majority (22 out of 29, 76%) used the saline tube without anti-human globulin (AHG) technique; one of these centers performs a 5-minute room temperature incubation before centrifugation. Most of the respondents stored the LTOWB as such for either 21 days (20 out of 37, 54%) or 14 days (13 out of 37, 35%). In the 2018 survey, half (8 out of 16, 50%) of the hospitals discarded an unused LTOWB unit, while some (6 out of 16, 38%) produce an RBC unit once the LTOWB unit reaches its maximum storage length. These figures have remained stable at 21 out of 37 (57%) and 13 out of 37 (35%), respectively, in the current survey. Given that in the USA a special license is not required for a hospital to manufacture an RBC unit from an LTOWB unit as long as the RBC is transfused at that institution, it is surprising that more hospitals do not avail themselves of this waste mitigation strategy. One hospital keeps LTOWB units available in the pre-hospital setting for up to 14 days and if they are not used in that setting, they are added to the hospital blood bank's LTOWB inventory for trauma patients for up to 35 days. Another hospital uses LTOWB units for trauma patients for up to 21 days; after that time they can be used for up to 35 days for other bleeding patients such as those in the operating room (listed as "Other" for Question 8 in Table 1). Eight American hospitals and the Norwegian hospital offer LTOWB for use in traumatically injured children. One American hospital has changed their requirements for pediatric LTOWB eligibility in the interval between the 2018 and the current survey; previously pediatric patients at that institute had to be at least 3 years old and weigh at least 15 kg,8 whereas the new requirement is only age ≥1 year old. This change was made to be able to provide LTOWB to more patients once the safety of transfusing LTOWB had been demonstrated at that institution. A second American health care system transfuses D+ LTOWB to traumatically injured children, both boys and girls, who are ≥5 years old in the pre-hospital setting only. Other eligibility criteria for administering LTOWB to children include weight >15, >20, >30 kg at three institutions, age ≥2 years old and weight ≥10 kg at an institution that transfuses only boys with LTOWB, age ≥1 in one of the air ambulance services, and a weight dependent dose (15-20 mL/kg) if the child weighs <35 kg at another American hospital. The Norwegian hospital does not have any requirements for qualifying pediatric recipients. Finally, 12 out of 37 (32%) of the hospitals surveyed do not perform any degree of laboratory testing for hemolysis amongst the LTOWB recipients (Question 12 in Table 1). This survey demonstrated the practice patterns for LTOWB in the USA and in several other countries. The practice remains quite variable in terms of how many units are available per patient, the definition of low titer anti-A and -B, and the storage length of the LTOWB units, and whether any testing for hemolysis occurs following LTOWB transfusion. The authors have disclosed no conflicts of interest.