Numerous clinical situations require emergent

TRANSFUSION BRIEF REPORT PRACTICE A case for stocking O D+ red blood cells in emergency room trauma bays Erin Meyer and Lynne Uhl BACKGROUND: AABB Standard 5.27 requires transfusion services to have a process for urgent release of blood before completion of compatibility testing. Our institution endorses a policy for the emergency release of group O, D+ red blood cells (RBC; O+ RBC) to males and females at least 50 years of age. Our emergency department (ED) stocks 4 O RBC units. To determine if O+ RBCs can replace ED O RBCs, we performed a retrospective review. STUDY DESIGN AND METHODS: Patients admitted to the ED between January 2001 and August 2011 and transfused emergency-release O RBCs were identified. Data were collected on sex, age, length of stay, clinical status, ABO/Rh, RBC transfusions, and RBC antibody screen results. RESULTS: A total of 498 ED O RBC units were transfused to 268 patients (168 male, 100 female). A total of 322 units were transfused to males and 114 to females at least 50 years of age. Thirty-nine (14%) were D with 18 receiving O+ RBCs. A total of 109 had follow-up antibody screens; one D patient developed alloanti-d. CONCLUSIONS: The findings support the placement of O+ RBCs in the ED. The majority of ED O RBCs (88%) went to patients who qualified for O+ RBCs; a minority (1.5%) of patients were D females less than 50 years of age. The rate of alloimmunization was low. ABBREVIATIONS: BIDMC = Beth Israel Deaconess Medical Center; ED = emergency department. From the Joint Fellowship Program in Transfusion Medicine & Department of Pathology, Beth Israel Deaconess Medical Center; and Harvard Medical School, Boston, Massachusetts. Address reprint requests to: Erin K. Meyer, DO, MPH, Emory University School of Medicine, Woodruff Memorial Research Building, 101 Woodruff Circle, Suite 7105-A, Atlanta, GA 30322; e-mail: emeyer5@emory.edu. Received for publication June 5, 2014; revision received September 16, 2014, and accepted September 16, 2014. doi: 10.1111/trf.12925 2014 AABB TRANSFUSION 2015;55:791 795. **;**:**-**. Numerous clinical situations require emergent blood transfusions. According to the 29th edition of Standards for Blood Banks and Transfusion Services, Standard 5.27 requires transfusion services to have a process in place allowing for the urgent release of red blood cells (RBCs) before completion of compatibility testing. 1 Traditionally as the universal donor group O, D RBC units have been used for emergent un cross-matched transfusions. The D antigen s immunogenicity is well documented. Yet the rate of anti-d formation is variable and appears to be dependent on the population transfused. Pollack and colleagues 2 transfused 500 ml of D+ blood to 22 D healthy volunteers and found the rate of alloimmunization to be 81.8% (18 of 22). Cook and Rush 3 in 1974 found in 20 D patients transfused an average of 19.4 D+ units per patient an alloimmunization rate of 95% (19/20). Yazer and Triulzi 4 retrospectively reviewed the transfusion records of 15 hospitals and found 98 D patients received 445 D+ RBC units. The rate of alloimmunization in this study population was approximately 22% (22/98). 4 Gonzalez-Porras and colleagues 5 prospectively evaluated the use of D+ blood in massively transfused patients including women of non child-bearing years and adult men. In 351 D patients who received 1032 D+ units, the incidence of anti-d alloimmunization was 21.4%. 5 Yet in bone marrow transplant patients, patients with solid tumors, and patients with AIDS, the rate of D alloimmunization in D patients after transfusion with D+ blood was less than 10%. 6-9 These rates certainly suggest that increasing immunologic compromise affects the incidence of D alloimmunization. 4,5 Anti-D, however, remains significant for females of child-bearing potential: 20% of pregnancies where maternal anti-d is detectable will have severe hemolytic disease of the newborn. 10 In the United States donor population, group O, D donors only account for approximately 9% of all donors. 11 Due to the limited availability of group O, D RBC units (O RBC), Beth Israel Deaconess Medical Center (BIDMC) endorses a policy for the emergent release of group O, D+ un cross-matched RBCs (O+ RBCs) to all males, regardless of age, and to all females at least 50 years old. Yet BIDMC currently stocks 4 O RBC units in a monitored refrigerator in the emergency department (ED). To Volume 55, Volume April 2015 **, ** ** TRANSFUSION 7911

MEYER AND UHL determine if O+ RBCs can reasonably replace the O RBCs stocked in the ED, we performed a retrospective medical record review of all the patients who received blood from the ED refrigerator during a 10-year period examining the use of O RBCs in patients who qualified for O+ RBCs based on our policy. MATERIALS AND METHODS Study population selection and review After institutional review board approval was obtained, patients who were admitted through the ED and transfused with emergency-released RBC units from a monitored ED refrigerator were identified through a computerized query of the Center for Clinical Computing (Boston, MA) blood bank computer database from January 2001 through August 2011. Patients current blood type and antibody screen, historic blood type and antibody screen (if available), and number and type of subsequent RBC units, apheresis platelet products, plasma units, and cryoprecipitate units were recorded. Additional data collected included dates and results of any posttransfusion RBC antibody history. In addition, each patient s electronic medical record was reviewed for data on sex, age, length of hospitalization, and clinical status. Patients were evaluated for subsequent anti-d formation if they had at least one antibody screen performed at least 7 days after admission. Serologic investigation RBC typing (forward and reverse typing) as well as D typing were performed by either manual tube or automated technology (Immucor, Inc., Norcross, GA). 12 Antibody screens were performed using polyethylene glycol indirect antiglobulin test (Gamma Biologicals, Inc., Houston, TX) and a three-cell screen (R 1R 1, R 2R 2, rr; Immucor, Inc.) according to institutional standard operating procedure with agglutination reactions read macrosopically in tube and graded from 0 to 4+ for patients evaluated between 2001 and 2007. In January 2008, solid-phase technology (Capture-R, Immucor, Inc.) using a two-cell screen (R 1R 1,R 2R 2) was introduced for antibody screens. In all instances, positive screening tests were followed by serologic investigation using a panel of 14 phenotypically defined RBCs (Immucor, Inc.) selected to identify antibody specificity. The results of each patient s admission antibody screen and antibody specificity, if observed, were recorded. Only D patients who received D+ units and had subsequent antibody screen(s) performed at least 7 days after transfusion of emergently released ED units were included for serologic follow-up. Statistical analysis All descriptive statistical calculations were performed with computer software (Excel 2010, Microsoft Corp., Redmond, WA). RESULTS Demographics of study population During the study period, 498 O emergency-released RBC units stored in the ED inventory were transfused to 268 patients (168 [63%] male and 100 [37%] female) during January 2001 through August 2011 (see Table 1). Males were transfused 322 O RBC units. Females 50 years and older were transfused 114 O RBC units and female patients less than 50 years of age were transfused 62 O RBC units (Table 1). D patients Thirty-nine of the 268 (14%) patients who received emergency-released blood from the ED refrigerator were D. Eighteen of these D patients required transfusion with D+ RBC units (mean, 9.6 units; median, 4.5 units; range, 1-32 units) during the course of their admission. Seven patients required massive transfusions (>10 units of RBCs transfused within 24 hr). Of the D patients who received D+ RBC, five did not survive beyond 6 days of admission and three did not have a follow-up type and antibody screen. These patients were not included in TABLE 1. Characteristics of patients transfused emergently released ED RBCs Recipient characteristics Total (n = 268) Male (n = 168, 63%) Female (n = 100, 37%) Age (years)* 54.5, 55 (16-97) 53, 52 (16-92) 58, 59 (17-97) D status D+: 86% D+: 86% D+: 82% D : 14% D : 14% D : 18% Number ED O RBC units transfused 498 (100) 322 of 498 (65) 50 years old: 114 of 498 (23) <50 years old: 62 of 498 (12) ED O RBC units transfused per patient* 1.9, 2 (1-4) 1.9, 2 (1-4) 1.8, 2 (1-4) Number receiving additional RBC units/additional 227 (85)/16, 6 (1-166) 146 (85)/12, 6 (1-166) 80 (79)/7, 4 (1-44) RBC units transfused per patient during admission* Length of stay (days)* 12, 6 (0-202) 12, 6 (0-202) 12, 7 (0-146) Mortality (within 7 days of admission) 119 (44) 85 (50) 34 (34) Number with any posttransfusion antibody screen 109 (41) 64 (38) 45 (45) * Data are expressed as mean, median (range) or number (%). 792 2 TRANSFUSION Volume **, 55, ** ** April 2015

O D+ RBCs RBCS IN EMERGENCY ROOMS serologic follow-up. Eight D patients survived 7 days past admission and had at least one follow-up antibody screen after this point (see Serologic follow-up ). These patients received an average of 12.3 D+ RBC units (median, 10 units; range, 1-27 units; Table 2). Serologic follow-up Eighty-six patients died within 7 days of admission from the injuries for which they were admitted and urgently transfused. Of the 182 patients who survived past 7 days (45 females), 179 had negative RBC antibody screens on admission. Six patients had positive antibody screens on admission and were switched to the appropriate antigennegative RBC units after identification. Only four of these patients were alive 7 days after admission. One was an D+ female age 65 with anti-jk(a) and anti-kell, and one was a 62-year-old female with partial D with anti-d and anti-e. The third was a D male (age 50) with anti-d, and the fourth an 89-year-old D female with anti-d. Overall 73 patients did not have a repeat antibody screen at BIDMC during the 10-year study period. A total of 109 patients had at least one repeat antibody screen at BIDMC performed on average 283 days after the emergent transfusion episode (median, 19 days; range, 2-3672 days). Of this group, two patients had a newly positive antibody screen (see Table 2): one 38-year-old group O, D male developed a warm autoantibody, anti-d, anti-c, and anti-e, and one 90-year-old group B, D female developed an anti-e. The male had been transfused 20 units of D+ RBCs during a 24-hour period and the female 6 units of D+ RBCs. The rate of anti-d formation in D patients who received D+ blood and had an antibody screen performed at least 7 days after emergent transfusion was 12.5% (one of eight) in this patient population. DISCUSSION Blood is an altruistic resource that can pose significant risk to patients and needs to be transfused judiciously. In some situations, emergent transfusion of RBCs is necessary and can be lifesaving, particularly in patients admitted through the ED. In an effort to be good stewards of the blood supply, BIDMC has a policy in place to safeguard O RBCs for the population most at risk from anti-d formation: D females of child-bearing potential (<50 years of age). The policy allows for the use of O+ RBCs for all men and women of at least 50 years of age. However, O RBCs are currently stocked in the monitored ED refrigerator, which can be used for any patient admitted to the ED who is in urgent need of blood transfusion. We sought to determine with this retrospective review whether or not the ED refrigerator could be stocked with group O, D+ RBCs by examining the characteristics of all patients transfused from this inventory over a 10-year period. TABLE 2. Characteristics of D recipients who received O+ RBCs and survived past 7 days and had at least one follow-up antibody screen Mortality (during study period)/died from injuries suffered on admission Length of stay (days) Antibody screen result on follow-up Length of serologic follow-up (days) Antibody screen on admission Number of O+ RBC units transfused outside ED Number of ED-released O RBC units transfused in ED Admission service ABO type Age (years) Sex 38 Male O Trauma 2 20 Negative 164 Positive (WAA, anti-d, C, E) 202 Alive/NA 47 Male B Trauma 2 27 Negative 26 Negative 29 Died/yes 90 Female B Gastrointestinal 2 6 Negative 10 Positive (anti-e) 14 Alive/NA 31 Male O Trauma 4 1 Negative 2003 Negative 24 Alive/NA 54 Female A Trauma 2 25 Negative 142 Negative 146 Died/no 74 Male O Vascular surgery 2 3 Negative 65 Negative 14 Alive/NA 50 Male A Gastrointestinal 1 2 Positive (anti-d) 280 Positive (anti-d) 36 Alive/NA 63 Male O Vascular surgery 1 14 Negative 16 Negative 40 Alive/NA Volume 55, Volume April 2015 **, ** ** TRANSFUSION 7933

MEYER AND UHL This 10-year retrospective review supports the placement of group O, D+ RBCs in the ED inventory. The majority of D RBCs stocked in the ED (436, 88%) were transfused to patients who qualified for group O, D+ RBCs per institutional policy: men and women at least 50 years of age. The patient population most at risk for the deleterious effects of anti-d alloimmunization (i.e., females of child-bearing potential [women < 50 years of age per institutional policy]) received only 12% of the group O, D ED units (62 units). Furthermore consistent with national demographics, 86% of the overall study population were D+ and were transfused 413 of the group O, D RBC (83%). 11 Similar to a recent study by Zalpuri and colleagues, 13 serologic follow-up in this study was limited to at least 7 days. Previously alloimmunized patients would most likely present with a positive antibody screen (even with a negative screen on admission) less than 7 days after reexposure due to amnestic response while a period of 7 days allows for a primary immune response. 13 Only two patients who survived past 7 days and had at least one additional follow-up antibody screen at our institution developed alloantibodies. Both patients were D patients and received D+ RBCs. One was a 38-year-old male who received 20 units of D+ RBCs within a 24-hour period and developed a warm autoantibody, anti-d, anti-c, and anti-e. The other was a 90-year-old female transfused 6 units of D+ RBCs within a 24-hour period who developed an anti-e. Thus overall the incidence of anti-d alloimmunization in the D patients who received D+ RBC was low (12.5%, one of eight) in our study population. The rate of D alloimmunization observed in this study (12.5%) is lower than that observed in other studies. Frohn and coworkers 14 studied the rate of anti-d alloimmunization in hospitalized D recipients of D+ RBCs and used statistical modeling to account for those patients who would have formed an alloantibody on follow-up but did not during the study period (November 1987-June 2002). Frohn and coworkers 14 cite stressinduced immune suppression as a potential reason for their study s low alloimmunization rate. This could also have played a role in our study population as many of our patients suffered traumatic injury which has been previously described as a major factor in stress-related immune suppression. 15-17 The derived alloimmunization rate of Frohn and colleagues 14 was 30.4%. However, Yazer and colleagues calculated the actual alloimmunization rate of Frohn and colleagues to be 21%, which is consistent with Yazer and Triulzi s observation in their multicenter retrospective review of an anti-d seroconversion rate of 22%. 4,14 The lower anti-d alloimmunization rate observed here may be related to the study s limitations. The data were collected retrospectively, and serologic follow-up was limited to only our institution. A prospective study would allow for a more complete follow-up on patients who receive their care at other institutions. Also complete transfusion, alloimmunization, and pregnancy histories were not available for all patients. In addition, our study had a relatively small number of subjects (268 patients) of which only 18 D were transfused D+ RBCs during their hospitalization. The results of this review suggest that the placement of group O, D+ RBC in the ED inventory should be considered. The majority of the units transfused (88%) from this inventory were given to patients who qualified for group O, D+ RBCs per institutional policy. In addition, only a minority of patients (4, 1.5%) were D females of childbearing potential (<50 years of age), 25% (one) of whom did not survive the injuries for which she was admitted and transfused. CONFLICT OF INTEREST The authors have disclosed no conflicts of interest. REFERENCES 1. American Association of Blood Banks. Standards for blood banks and transfusion services. 29th ed. Bethesda (MD): American Association of Blood Banks; 2014. 2. Pollack W, Ascari WQ, Crispen JF, et al. Studies on Rh prophylaxis II. Rh immune prophylaxis after transfusion with Rh-positive blood. Transfusion 1971;11:340-4. 3. Cook K, Rush B. Rh(D) immunization after massive transfusion of Rh(D)-positive blood. Med J Aust 1974;1: 166-8. 4. Yazer MH, Triulzi DJ. Detection of anti-d in D recipients transfused with D+ red blood cells. Transfusion 2007;47: 2197-201. 5. Gonzalez-Porras JR, Graciani IF, Perez-Simon JA, et al. Prospective evaluation of a transfused policy of D+ red blood cells into D patients. Transfusion 2008;48:1318-24. 6. Schonewille H, Haak HL, van Zijl AM. Alloimmunization after blood transfusion in patients with hematologic and oncologic diseases. Transfusion 1999;39:763-71. 7. Baldwin ML, Ness PM, Scott D, et al. Alloimmunization to D antigen and HLA in D- immunosuppressed oncology patients. Transfusion 1988;28:330-3. 8. Holohan TV, Terasaki PI, Deisseroth AB. Suppression of transfusion-related alloimmunization in intensively treated cancer patients. Blood 1981;58:122-8. 9. Asfour M, Narvios A, Lichtiger B. Transfusion of RhD incompatible blood components in RhD-negative blood marrow transplant recipients. MedGenMed 2004;6:22. 10. Eder AF, Manno CS. Alloimmune hemolytic disease of the fetus and newborn. In: Means R, Foerester J, Greer JP, et al., editors. Wintrobe s clinical hematology. 12th ed. Philadelphia (PA): Lippincott, Williams and Wilkins; 2009. p. 978. 794 4 TRANSFUSION Volume **, 55, ** ** April 2015

O D+ RBCs RBCS IN EMERGENCY ROOMS 11. American Association of Blood Banks. Frequently asked questions. Updated August 6, 2013. [cited 2014 May 21]. Available from: http://www.aabb.org/tm/pages/bloodfaq/ aspx#a8 12. Roback JD, Grossman BJ, Harris T, et al., editors. Technical manual. 17th ed. Bethesda (MD): American Association of Blood Banks; 2011. 13. Zalpuri S, Middelburg RA, Schonewille H, et al. Intensive red blood cell transfusions and risk of alloimmunization. Transfusion 2014;54:278-84. 14. Frohn C, Dümbgen L, Brand JM, et al. Probability of anti-d development in D patients receiving D+ RBCs. Transfusion 2003;43:893-8. 15. Hotchkiss RS, Tinsley KW, Swanson PE, et al. Sepsis inducted apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol 2001; 166:6952-63. 16. Puyana JC, Pellegrini JD, De AK, et al. Both T-helper-1 and T-helper-2-type lymphokines are depressed in posttrauma anergy. J Trauma 1998;44:1037-45. 17. Hensler T, Hecker H, Heeg K, et al. Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun 1997;65:2283-91. Volume 55, Volume April 2015 **, ** ** TRANSFUSION 7955