Abstract
The purpose of this study was to evaluate the extent to which a blood bank policy aimed at decreasing the risk of hemolytic disease of the fetus and newborn (HDFN) by limiting emergency-release blood to Rh-negative blood products is effective. We conducted a retrospective review of the trauma registry for all trauma patients evaluated at our level II trauma center. Patients who received blood products within 4 h of arrival were included. Focused chart review was performed to describe the ABO type, Rh blood type, and sex of the blood recipient in the study population. We identified 262 patients who received emergent transfusion, including 64 women. Four of the 64 women (6%) were Rh negative. Of these, one was of childbearing potential, which represents 0.4% of the 262 patients who received emergency-release blood products and 1.6% of the 64 women emergently transfused following trauma. During our study interval, 1527 units of blood were transfused to patients who could have received Rh-positive blood without concern for HDFN. The proscription against Rh-positive blood as an emergency-release blood product only minimally reduces the risk of development of future HDFN in our trauma population.
Keywords: ABO blood group, emergency transfusion, hemolytic disease of the fetus and newborn, low titer whole blood, Rh blood group, trauma
The use of cold-stored low-titer O Rh-positive whole blood (LTOWB) in trauma is becoming more widespread in the civilian trauma system. Concerns exist over the risk this poses to Rh alloimmunization of Rh-negative women of childbearing potential who receive emergency LTOWB. If such an alloimmunization were to occur, the Rh-negative woman would be at risk of hemolytic disease of the fetus and newborn (HDFN) if she subsequently conceived a child who was Rh-positive. The purpose of this study was to evaluate if blood bank policy aimed at decreasing the risk of HDFN by limiting emergency-release blood in the trauma bay to Rh-negative blood products is effective and feasible as the use of LTOWB becomes more prevalent. To do this, we quantified the number of trauma patients seen at our institution for whom this policy would potentially protect from future HDFN.
METHODS
This retrospective review of the prospectively maintained trauma registry was conducted for all trauma patients evaluated at our American College of Surgeons–verified level II trauma center since its inception. This period spanned 3 years and 7 months, from January 1, 2016, to July 31, 2019. The Texas Health Resources institutional review board approved this study. The trauma registry (Trauma One v4.21, Lancet Technology, Inc.) was queried for all patients meeting the standards for inclusion in the National Trauma Data Bank. Data elements queried included age, sex, race and ethnicity, emergency department disposition, injury type (i.e., blunt, penetrating), injury severity score, and number of blood products transfused.
We further identified all patients who received a blood product transfusion, as well as those who received blood products within 4 h of arrival. The EPIC electronic health record (EPIC Hyperspace®, Epic Systems Corporation) was used to access patient charts for blood type and Rh factor among those patients who received blood products within 4 h of arrival to the hospital. This population was selected for analysis, as they were most likely to receive emergency-release un–cross-matched type O Rh-negative blood. This represents the population that would be protected by limiting emergently released blood to O Rh-negative products. Patients for whom no blood type was available in the medical record were excluded from analysis.
RESULTS
During the study interval, 7681 trauma patients were identified in the trauma registry. Of these, 883 patients received a blood product transfusion over the course of their hospitalization. Of those who received a transfusion, 277 patients received blood products within 4 h of arrival. Blood type was not available for 15 patients, who were excluded, leaving 262 patients who received emergency-release blood products for analysis (see Figure 1). This cohort had a median age of 37 years (interquartile range [IQR] 26–57), had a median injury severity score of 22 (IQR 12–33), and was predominantly male (n = 198, 76%), with only 24% of these patients being female (n = 64) (Table 1). Consistent with early transfusion after arrival, these patients suffered higher rates of penetrating injury than our overall trauma population, with 52% (n = 144) experiencing blunt trauma and 42% (n = 118) experiencing penetrating trauma. Additionally, 35% of patients (n = 98) in this cohort received >10 units of blood products, consistent with a massive transfusion. Table 1 shows patient demographic information for the three cohorts.
Figure 1.
Patients included in the analysis. DOA indicates deceased upon arrival; ED, emergency department; NTDB, National Trauma Data Bank; OR, operating room.
Table 1.
Characteristics of patients included in the trauma registry, January 1, 2016–July 31, 2019
| Characteristic | All trauma patients (n = 7681) | All trauma patients transfused (n = 883) | All trauma patients transfused within 4 h (n = 277) a | |
|---|---|---|---|---|
| Age (years), median (IQR) | 54 (30–77) | 68 (39–83) | 37 (26–57) | |
| Female | 3523 (46%) | 439 (50%) | 64 (24%) | |
| Race | ||||
| Black | 868 (11%) | 127 (14%) | 65 (23%) | |
| White | 5766 (75%) | 723 (82%) | 181 (65%) | |
| Asian | 164 (2%) | 18 (2%) | 4 (1%) | |
| Other/unknown | 883 (12%) | 15 (2%) | 27 (8%) | |
| Ethnicity | ||||
| Hispanic | 1268 (17%) | 133 (15%) | 70 (25%) | |
| Non-Hispanic | 5605 (73%) | 737 (84%) | 185 (67%) | |
| Unknown | 808 (11%) | 13 (1%) | 7 (8%) | |
| Emergency department disposition | ||||
| AMA | 32 | 0 | 0 | |
| Cath lab/IR | 41 | 23 | 0 | |
| Died in ED | 48 | 13 | 11 | |
| DOA | 86 | 16 | 4 | |
| Admit to floor | 6688 | 363 | 9 | |
| Home | 1823 | 0 | 0 | |
| Admit to ICU | 1331 | 234 | 75 | |
| L&D | 34 | 0 | 0 | |
| Telemetry | 217 | 10 | 0 | |
| Observation | 522 | 14 | 2 | |
| OR | 867 | 206 | 141 | |
| Transferred out | 574 | 1 | 1 | |
| Other/no info | 160 | 3 | 2 | |
| ISS, median (IQR) | 9 (4–10) | 10 (9–22) | 22 (13–33) | |
| Blunt injury | 6885 (90%) | 739 (84%) | 144 (52%) | |
Patients with no blood type information (n = 15) are excluded from this set.
AMA indicates against medical advice; DOA, deceased on arrival; ICU, intensive care unit; IQR, interquartile range; IR, interventional radiology; ISS, injury severity score; L&D, labor and delivery; OR, operating room.
As shown in Table 2, of the 64 women in this cohort, 4 were Rh negative (6%). Of these, 1 was of childbearing age (31 years old). Thus, the number of women of childbearing potential who were also Rh negative and received emergency-release blood products represents 0.4% of the 262 patients who received blood products within 4 h of arrival at our trauma center over an almost 4-year period. This one patient also represents <2% of all women transfused after trauma within 4 h of arrival (n = 64) over our study period.
Table 2.
ABO and Rh blood types, for all 4-hour transfused patients
| Blood group | Subgroup | Rh positive | Rh negative | Total |
|---|---|---|---|---|
| A | All | 72 (27%) | 10 (4%) | 82 (31%) |
| Female | 24 (38%) | 1 (2%) | 25 (36%) | |
| B | All | 29 (11%) | 3 (1%) | 32 (12%) |
| Female | 7 (11%) | 0 | 7 (11%) | |
| AB | All | 8 (3%) | 0 | 8 (3%) |
| Female | 2 (3%) | 0 | 2 (3%) | |
| O | All | 124 (47%) | 16 (6%) | 140 (53%) |
| Female | 27 (42%) | 3 (5%) | 30 (47%) | |
| Total | All | 233 (89%) | 29 (11%) | 262 |
| Female | 60 (94%) | 4 (6%) | 65 |
DISCUSSION
There has been renewed interest in whole blood transfusion since the US military began utilizing it during recent conflicts in the Middle East. The military experience favors whole blood, as it is easier to both procure (“walking blood banks”) and store in austere environments. 1 Additionally, whole blood utilization demonstrates trends toward improved survival. 2 A small series from 2016 subsequently demonstrated safety in a civilian trauma center setting. 3 Recent experience suggests that whole blood resuscitation leads to improved trauma bay survival and offers a balanced and efficient resuscitation in massive hemorrhage. 4
Preventing HDFN is an important consideration in transfusion medicine. This disease has a range of severity, from mild anemia to severe anemia with deleterious effects on end organs of the fetus and the potential for fetal demise if left untreated. However, treatment of Rh-negative women who have received Rh-positive blood is possible and very successful at preventing subsequent alloimmunization. 5 A recent longitudinal study by Delaney et al demonstrated that among women who were treated for severe HDFN (n = 293) over a 12-year period at multiple large institutions, most alloimmunization (83%) was attributed to exposure in a previous pregnancy. 6 Alloimmunization was attributed to transfusion in only 8 patients (3%), with 14% of cases having undetermined etiology (both antecedent transfusion and pregnancy). The most common indication for transfusion was obstetric hemorrhage. 6 For these 293 mothers, 835 pregnancies occurred over the 12-year study period. A total of 425 (51%) of the 835 pregnancies were affected by severe HDFN. Overall survival of all infants born to these mothers was >90% over the study period, thanks to available treatment including intrauterine blood transfusion. Additionally, it is common practice in obstetrics to screen for Rh factor and administer Rh immune globulin as needed postpartum to reduce the risk for HDFN in subsequent pregnancies. This therapy is remarkably effective at preventing alloimmunization, reducing the risk from 16% to <1% in Rh-negative mothers. 5 , 7 Additionally, the risk of alloimmunization among Rh-negative patients receiving Rh-positive blood is estimated to be 21% to 26%, further reducing the population at risk for this disease process. 8
To avoid the risk of HDFN in transfusion medicine, it is common practice to use O Rh-negative blood as the initial emergent transfusion product of choice until a blood type antibody screening test can be performed and the gender of the patient confirmed. In the US, approximately 7% of donors are group O Rh negative, yet this blood product comprises >10.8% of transfused products. 8 During our study interval, 1527 units of blood were transfused to patients who could receive Rh-positive blood without concern for HDFN (Table 3).
Table 3.
Number of units of red blood cells used by each blood type in the first 4 h
| Blood group | Subgroup | Rh positive | Rh negative | Total |
|---|---|---|---|---|
| A | All | 415 (27%) | 62 (4%) | 477 (31%) |
| Female | 71 (29%) | 4 (2%) | 75 (31%) | |
| B | All | 184 (12%) | 28 (2%) | 212 (14%) |
| Female | 48 (20%) | 0 | 48 (20%) | |
| AB | All | 54 (4%) | 0 | 54 (4%) |
| Female | 3 (1%) | 0 | 3 (1%) | |
| O | All | 725 (47%) | 68 (4%) | 793 (52%) |
| Female | 110 (46%) | 5 (2%) | 115 (48%) | |
| Total | All | 1378 (90%) | 158 (10%) | 1536 |
| Female | 232 (96%) | 9 (4%) | 241 |
The proscription against Rh-positive blood as an emergency-release blood product is likely overstated in the context of our trauma population. This practice places considerable strain on a scarce supply of Rh-negative blood products. Our study demonstrates that the prevalence of Rh-negative women of childbearing potential requiring emergent transfusion after trauma represents an extremely small cohort of patients (n = 1) over a > 3-year time frame at our institution. This is a combined effect of our low population of Rh-negative patients in North Texas and the predominance of men among our severely injured trauma cohort. While more liberal transfusion practices will risk the possibility of HDFN, a robust program to monitor women who receive emergency-release O Rh-positive blood should be capable of capturing and treating those at risk. Such programs have been successfully implemented at other major trauma centers across the country. 7
Since death from hemorrhage remains a leading cause of mortality among trauma patients, having a readily available, safe, and effective transfusion product represents an opportunity to save lives. Emergency-release LTOWB represents one such opportunity with minimal risk to our patient population.
References
- 1. Vanderspurt CK, Spinella PC, Cap AP, et al. The use of whole blood in US military operations in Iraq, Syria, and Afghanistan since the introduction of low-titer Type O whole blood: feasibility, acceptability, challenges. Transfusion. 2019;59(3):965–970. doi: 10.1111/trf.15086. [DOI] [PubMed] [Google Scholar]
- 2. Spinella PC. Warm fresh whole blood transfusion for severe hemorrhage: U.S. military and potential civilian applications. Crit Care Med. 2008;36(7 Suppl):S340–S345. doi: 10.1097/CCM.0b013e31817e2ef9. [DOI] [PubMed] [Google Scholar]
- 3. Yazer MH, Jackson B, Sperry JL, Alarcon L, Triulzi DJ, Murdock AD.. Initial safety and feasibility of cold-stored uncrossmatched whole blood transfusion in civilian trauma patients. J Trauma Acute Care Surg. 2016;81(1):21–26. doi: 10.1097/TA.0000000000001100. [DOI] [PubMed] [Google Scholar]
- 4. Hazelton JP, Cannon JW, Zatorski C, et al. Cold-stored whole blood: a better method of trauma resuscitation? J Trauma Acute Care Surg. 2019;87(5):1035–1041. doi: 10.1097/TA.0000000000002471. [DOI] [PubMed] [Google Scholar]
- 5. Delaney M, Matthews DC.. Hemolytic disease of the fetus and newborn: managing the mother, fetus, and newborn. Hematology. 2015;2015(1):146–151. doi: 10.1182/asheducation-2015.1.146. [DOI] [PubMed] [Google Scholar]
- 6. Delaney M, Wikman A, van de Watering L, et al. Blood group antigen matching influence on gestational outcomes (AMIGO) study. Transfusion. 2017;57(3):525–532. doi: 10.1111/trf.13977. [DOI] [PubMed] [Google Scholar]
- 7. McGinity AC, Zhu CS, Greebon L, et al. Prehospital low-titer cold-stored whole blood: philosophy for ubiquitous utilization of O-positive product for emergency use in hemorrhage due to injury. J Trauma Acute Care Surg. 2018;84(6S Suppl 1):S115–S119. doi: 10.1097/TA.0000000000001905. [DOI] [PubMed] [Google Scholar]
- 8. Murphy M, BenAvram D.. Recommendations on the Use of Group O Red Blood Cells. Bethesda, MD: AABB; 2019. [Google Scholar]

