Ethical considerations in the use of RhD-positive blood products in trauma.

BACKGROUND: Prehospital and early in-hospital use of low titer group O whole blood (LTOWB) for life-threatening bleeding has been independently associated with improved survival compared to component therapy. However, when RhD-positive blood products are administered to RhD-negative females of childbearing potential (FCP), there is a small future risk of hemolytic disease of the fetus and newborn (HDFN). This raises important ethical questions that must be explored in order to justify the use of RhD-positive blood products, including LTOWB, both in clinical practice and research. METHODS: This essay explores the ethical challenges related to RhD-positive blood product administration to RhD-negative or RhD-unknown FCPs as a first-line resuscitation fluid in the trauma setting. These ethical issues include: issues related to decision-making, ethical analysis based on the doctrine of double effect (DDE), and attendant obligations incurred by hospitals that administer RhD-positive blood to FCPs. RESULTS: Ethical analysis through the use of the DDE demonstrates that utilization of RhD-positive blood products, including LTOWB, in the early resuscitation of FCPs is an ethically appropriate approach. By accepting the risk of HDFN, hospitals generate obligations to promote blood donation, evaluate for alloimmunization and counsel patients on the future risk of HDFN, and maintain an understanding of the ethical rationale for RhD-positive blood transfusion.

Survey of policies at US hospitals on the selection of RhD type of low-titer O whole blood for use in trauma resuscitation.

BACKGROUND: Low-titer group O whole blood (LTOWB) use is increasing due to data suggesting improved outcomes and safety. One barrier to use is low availability of RhD-negative LTOWB. This survey examined US hospital policies regarding the selection of RhD type of blood products in bleeding emergencies. STUDY DESIGN AND METHODS: A web-based survey of blood bank directors was conducted to determine their hospital's RhD-type selection policies for blood issued for massive bleeding. RESULTS: There was a 61% response rate (101/157) and of those responses, 95 were complete. Respondents indicated that 40% (38/95) use only red blood cells (RBCs) and 60% (57/95) use LTOWB. For hospitals that issue LTOWB (N = 57), 67% are supplied only with RhD-positive, 2% only with RhD-negative, and 32% with both RhD-positive and RhD-negative LTOWB. At sites using LTOWB, RhD-negative LTOWB is used exclusively or preferentially more commonly in adult females of childbearing potential (FCP) (46%) and pediatric FCP (55%) than in men (4%) and boys (24%). RhD-positive LTOWB is used exclusively or preferentially more commonly in men (94%) and boys (54%) than in adult FCP (40%) or pediatric FCP (21%). At sites using LTOWB, it is not permitted for adult FCPs at 12%, pediatric FCP at 21.4%, and boys at 17.1%. CONCLUSION: Hospitals prefer issuing RhD-negative LTOWB for females although they are often ineligible to receive RhD-negative LTOWB due to supply constraints. The risk and benefits of LTOWB compared to the rare occurrence of hemolytic disease of the fetus/newborn (HDFN) need further examination in the context of withholding a therapy for females that has the potential for improved outcomes.

Receipt of RhD-positive whole blood for life-threatening bleeding in female children: A survey in alloimmunized mothers regarding minimum acceptable survival benefit relative to risk of maternal alloimmunization to anti-D.

BACKGROUND: Low-titer group O whole blood (LTOWB) for treatment of hemorrhagic shock sometimes necessitates transfusion of RhD-positive units due to short supply of RhD-negative LTOWB. Practitioners must choose between using RhD-positive LTOWB when RhD-negative is unavailable against the risk to a female of childbearing potential of becoming RhD-alloimmunized, risking hemolytic disease of the fetus and newborn (HDFN) in future children, or using component therapy with RhD-negative red cells. This survey asked females with a history of red blood cell (RBC) alloimmunization about their risk tolerance of RhD alloimmunization compared to the potential for improved survival following transfusion of RhD-positive blood for an injured RhD negative female child. STUDY DESIGN AND METHODS: A survey was administered to RBC alloimmunized mothers. Respondents were eligible if they were living in the United States with at least one red cell antibody known to cause HDFN and if they had at least one RBC alloimmunized pregnancy. RESULTS: Responses from 107 RBC alloimmmunized females were analyzed. There were 32/107 (30%) with a history of severe HDFN; 12/107 (11%) had a history of fetal or neonatal loss due to HDFN. The median (interquartile range) absolute improvement in survival at which the respondents would accept RhD-positive transfusions for a female child was 4% (1%-14%). This was not different between females with and without a history of severe or fatal HDFN (p = .08 and 0.38, respectively). CONCLUSION: Alloimmunized mothers would accept the risk of D-alloimmunization in a RhD-negative female child for improved survival in cases of life-threatening bleeding.

Delayed Leukoreduction of whole blood with a platelet-sparing filter to increase low-titer group O whole blood production in the United States.

BACKGROUND: Demand for low-titer Group O whole blood (LTOWB) is increasing for trauma. The whole blood (WB) platelet-sparing (WB-SP) filter enables leukoreduction (LR) while retaining platelet quantity and function; however, in the United States WB must be filtered and placed in the cold within 8 h of collection. A longer processing window would facilitate improved logistics and supply of LR-WB to meet the growing medical need. This study evaluated the impact of increasing filtration timing from <8 h to <12 h on the quality of LR-WB. STUDY DESIGN AND METHODS: Thirty WB units were collected from healthy donors. Control units were filtered within 8 h and test units within 12 h of collection. WB was tested throughout 21 days of storage. Hemolysis, WBC content, component recovery, and 25 additional markers of WB quality were tested including hematologic and metabolic markers, RBC morphology, aggregometry, thromboelastography, and p-selectin. RESULTS: There were 0 failures for residual WBC content, hemolysis, or pH, and no differences in component recovery between arms. Few differences in metabolic parameters were observed, but the small effect size suggests these are not clinically significant. Trends throughout storage were similar and filtration timing did not impact hematological parameters, platelet activation and aggregation, or hemostatic capacity. CONCLUSION: Our studies showed that extending filtration timing from 8 to 12 h from the collection does not significantly impact the quality of LR-WB. Characterization of the platelets demonstrated that storage lesions were not exacerbated. Extending the time from collection to filtration will improve LTOWB inventory in the United States.

Transfusion of ABO-group identical red blood cells following uncrossmatched transfusion does not lead to higher mortality in civilian trauma patients.

BACKGROUND: Questions persist about the safety of switching non-group O recipients of group O uncrossmatched red blood cells (RBC) or low titer group O whole blood (LTOWB) to ABO-identical RBCs during their resuscitation. METHODS: The database of an earlier nine-center study of transfusing incompatible plasma to trauma patients was reanalyzed. The patients were divided into three groups based on 24-h RBC transfusion: (1) group O patients who received group O RBC/LTOWB units (control group, n = 1203), (2) non-group O recipients who received only group O units (n = 646), (3) non-group O recipients who received at least one unit of group O and non-group O units (n = 562). Fixed marginal effect of receipt of non-O RBC units on 6- and 24-h and 30-day mortality was calculated. RESULTS: The non-O patients who received only group O RBCs received fewer RBC/LTOWB units and had slightly but significantly lower injury severity score compared to control group; non-group O patients who received both group O and non-O units received significantly more RBC/LTOWB units and had a slightly but significantly higher injury severity score compared to control group. In the multivariate analysis, the non-O patients who received only group O RBCs had significantly higher mortality at 6-h compared to the controls; the non-group O recipients of O and non-O RBCs did not demonstrate higher mortality. At 24-h and 30-days, there were no differences in survival between the groups. CONCLUSION: Providing non-group O RBCs to non-group O trauma patients who also received group O RBC units is not associated with higher mortality.

Stewardship of Prehospital Low Titer O-Positive Whole Blood in a Large Urban Fire-Based EMS System.

Introduction: Trauma is the leading cause of death for those aged 1 to 46 years with most fatalities resulting from hemorrhage prior to arrival to hospital. Hemorrhagic shock patients receiving transfusion with 15 minutes experience lower mortality. Prehospital blood transfusion has many legal, fiduciary, and logistical issues. The San Antonio Fire Department participates in a consortium designed to enhance the stewardship of prehospital whole blood. This study aimed to stratify blood usage amongst the field supervisors and special operations units that carry whole blood. Methods: This was a 12-month retrospective analysis of blood usage. Blood tracking forms (used for either blood exchange of transfusion) were cross referenced with city financial records to determine blood usage patterns in the 7th Largest City in the US. We used descriptive statistics, compared usage ratios, and chi-square to compare dichotomized data. Results: A total of 363 whole blood units were obtained and 248 (68.3%) units of whole blood were transfused. EMS field supervisors transfused 74% of whole blood vs. 44% for special operations ambulances (p= <0.001). Response vehicles located in densely populated areas had the highest usage rates. All blood units were either transfused or returned for a zero blood unit wastage for expiration. Conclusion: The information contained within this work can provide other EMS agencies with a basic framework for comparison. The data from the SAFD's whole blood transfusion rate coupled with the clinical transfusion guideline has provided some insight for prospective agencies considering adopting a whole blood program. EMS systems and municipalities with similar characteristics can project their own whole blood needs and make informed decisions regarding program feasibility and design.

Opportunities for standardization of cold stored, low-titre group O WB products.

Interest in the use of cold-stored low-titre, group O whole blood (LTO-WB) in civilian trauma medicine has motivated regional and national blood services to explore the operational implications of providing this product to their hospital customers. While simpler to produce, store and administer than conventional blood components, LTO-WB is only distributed by a limited number of civilian blood services to date. To improve the availability of LTO-WB, there are still a number of clinical and basic research challenges that need to be addressed including 1. Standardization of the methods and definitions for what constitutes "low-titre" whole blood; 2. Updating regulatory standards for the in vitro quality of cold stored whole blood; 3. Development of standards for the post-storage component separation of red blood cells from cold stored whole blood; and 4. Optimization of the logistics for collection and distribution of cold stored whole blood in regional and national blood systems. The main objective of this concise overview is to highlight the opportunities for future research and product development efforts that will improve the availability of standardised LTO-WB products in emergency cases to the benefit of all concerned.

Advanced Critical Care Techniques in the Field.

Critical care principles and techniques continue to hold promise for improving patient outcomes in time-dependent diseases encountered by emergency medical services such as cardiac arrest, acute ischemic stroke, and hemorrhagic shock. In this review, the authors discuss several current and evolving advanced critical care modalities, including extracorporeal cardiopulmonary resuscitation, resuscitative endovascular occlusion of the aorta, prehospital thrombolytics for acute ischemic stroke, and low-titer group O whole blood for trauma patients. Two important critical care monitoring technologies-capnography and ultrasound-are also briefly discussed.

Not as "D"eadly as once thought - the risk of D-alloimmunization and hemolytic disease of the fetus and newborn following RhD-positive transfusion in trauma.

The use of blood products to resuscitate injured and massively bleeding patients in the prehospital and early in-hospital phase of the resuscitation is increasing. Using group O red blood cells (RBC) and low titer group O whole blood (LTOWB) avoids an immediate hemolytic reaction from recipient's naturally occurring anti-A and - B, but choosing the RhD type for these products is more nuanced and requires the balancing of product availability and survival benefit against the risk of D-alloimmunization, especially in females of childbearing potential (FCP) due to the possible future occurrence of hemolytic disease of the fetus and newborn (HDFN). Recent models have estimated the risk of fetal/neonatal death from HDFN resulting from D-alloimmunization of an FCP during her trauma resuscitation at between 0-6.5% depending on her age at the time of the transfusion and other societal factors including trauma mortality, her age when she becomes pregnant, frequency of different RHD genotypes in the population, and the probability that the woman will have children with different fathers; this is counterbalanced by an approximately 24% risk of death from hemorrhagic shock. This review will discuss the different models of HDFN outcomes following RhD-positive transfusion as well as the results of recent surveys where the public was asked about their preferences for urgent transfusion in light of the risks of fetal/neonatal adverse events.

The Use of Whole Blood Transfusion in Trauma.

Purpose of Review: This review illustrates the current benefits, limitations, ongoing research, and future paths for Low Titer O Whole Blood compared to Component Therapy in massive transfusion for trauma patients. Recent Findings: Many studies show that compared to Component Therapy, Low Titer O Whole Blood transfusion is associated with better patient outcomes and simplified transfusion logistics among others. There are, however, issues with cost, supply/demand and handling of Whole Blood that limit its use, but experience in the military setting has shown that these limitations can be easily overcome. Summary: The use of Whole Blood has increased in the civilian trauma population and there is a growing body of evidence to support its current use. More research looking at Whole Blood in females of child-bearing age, pediatric populations, and cold-stored platelets is underway.