Red Blood Cell Transfusion in European Neonatal Intensive Care Units, 2022 to 2023.

Importance: Red blood cell (RBC) transfusions are frequently administered to preterm infants born before 32 weeks of gestation in the neonatal intensive care unit (NICU). Two randomized clinical trials (Effects of Transfusion Thresholds on Neurocognitive Outcomes of Extremely Low-Birth-Weight Infants [ETTNO] and Transfusion of Prematures [TOP]) found that liberal RBC transfusion thresholds are nonsuperior to restrictive thresholds, but the extent to which these results have been integrated into clinical practice since publication in 2020 is unknown. Objective: To describe neonatal RBC transfusion practice in Europe. Design, Setting, and Participants: This international prospective observational cohort study collected data between September 1, 2022, and August 31, 2023, with a 6-week observation period per center, from 64 NICUs in 22 European countries. Participants included 1143 preterm infants born before 32 weeks of gestation. Exposure: Admission to the NICU. Main Outcomes and Measures: Study outcome measures included RBC transfusion prevalence rates, cumulative incidence, indications, pretransfusion hemoglobin (Hb) levels, volumes, and transfusion rates, Hb increment, and adverse effects of RBC transfusion. Results: A total of 1143 preterm infants were included (641 male [56.1%]; median gestational age at birth, 28 weeks plus 2 days [IQR, 26 weeks plus 2 days to 30 weeks plus 2 days]; median birth weight, 1030 [IQR, 780-1350] g), of whom 396 received 1 or more RBC transfusions, totaling 903 transfusions. Overall RBC transfusion prevalence rate during postnatal days 1 to 28 was 3.4 transfusion days per 100 admission days, with considerable variation across countries, only partly explained by patient mix. By day 28, 36.5% (95% CI, 31.6%-41.5%) of infants had received at least 1 transfusion. Most transfusions were given based on a defined Hb threshold (748 [82.8%]). Hemoglobin levels before transfusions indicated for threshold were below the restrictive thresholds set by ETTNO in 324 of 729 transfusions (44.4%) and TOP in 265 of 729 (36.4%). Conversely, they were between restrictive and liberal thresholds in 352 (48.3%) and 409 (56.1%) transfusions, respectively, and above liberal thresholds in 53 (7.3%) and 55 (7.5%) transfusions, respectively. Most transfusions given based on threshold had volumes of 15 mL/kg (470 of 738 [63.7%]) and were administered over 3 hours (400 of 738 [54.2%]), but there was substantial variation in dose and duration. Conclusions and Relevance: In this cohort study of very preterm infants, most transfusions indicated for threshold were given for pretransfusion Hb levels above restrictive transfusion thresholds evaluated in recent trials. These results underline the need to optimize practices and for implementation research to support uptake of evidence.

Huaxi integrated blood management reduces the red blood cell transfusion for on-pump cardiac surgery: A quasi-experimental study.

OBJECTIVE: As many as half of patients undergoing on-pump cardiac surgery require red blood cell transfusion, emphasizing the need for effective strategies that can reduce this need. We conducted this analysis to assess the effectiveness of Huaxi Integrated Blood Management strategy at our medical center. DESIGN: Before and after study. PARTICIPANTS: Patients who underwent on-pump cardiac surgery were included from January 2019 to December 2021. Two cohorts were compared, one before implementation of the strategy (1 January 2019 until 31 May 2020) and one after implementation (1 June 2020 until 31 December 2021). MEASUREMENTS: We evaluated temporal trends in blood transfusion, safety, and efficacy of this strategy. Primary outcomes were the incidence and volume of intra- and postoperative blood transfusions of packed red blood cells. Secondary outcomes are intraoperative and postoperative transfusion of other blood products, all-cause mortality during hospitalization, and incidence of new-onset complications. MAIN RESULTS: Our results demonstrated that this integrated strategy effectively decreased both the perioperative packed red blood cell transfusion volume and incidence for patients who underwent the on-pump cardiac surgery. Following the implementation, the incidence of packed red blood cell transfusions decreased by 8.1% during the intraoperative period and by 12.3% during the postoperative period. The mean volume of such transfusions decreased by 0.28 units during the intraoperative period and by 0.49 units during the postoperative period. Hemoglobin concentrations were significantly higher after implementation, and the maximal mean increase was 4.72 g/l on postoperative day 1. Similar benefit of the strategy was observed across subgroups of patients who underwent different types of surgery. CONCLUSIONS: The Huaxi Integrated Blood Management strategy may be effective at reducing the need for packed red blood cell transfusion and enhancing patient care.

Evaluation of staged autologous blood transfusion during extracorporeal membrane oxygenation decannulation: A retrospective study.

BACKGROUND: Clinical blood resources are scarce and autologous blood transfusion for extracorporeal membrane oxygenation (ECMO) withdrawal is less studied. OBJECTIVES: To assess the use of staged autotransfusion during ECMO decannulation. METHODS: The study included ECMO withdrawal patients. Patients in the autologous transfusion group underwent staged transfusion during ECMO withdrawal, while those in the control group received 2.0 units of allogeneic packed red blood cells (RBCs) to increase hemoglobin (Hb). Parameters such as Hb, hematocrit (Hct), adverse events, decannulation success rate, volume of allogeneic RBC transfusions, and transfusion costs were compared. RESULTS: A total of 82 Chinese patients were enrolled, with a mean age of 46 years, 27 were female, and the top three primary diagnoses were cardiac arrest, acute myocarditis, and severe pneumonia. There were 41 individuals in the autologous blood transfusion group and 41 in the control group. No significant differences were observed in Hb, Hct, adverse events, and the success rate for decannulation between the two groups (all P > 0.05). Compared with the control group, the volume of allogeneic RBC transfusions [0 (0∼1.50) U vs. 3.5 (1.88∼40) U, P < 0.001] and the total cost [130 (130∼390) Chinese Yuan (CNY) vs. 910 (487.50, 1040) CNY, P = 0.002] were lower in the autologous transfusion group. CONCLUSION: In comparison with allogeneic RBC transfusion, staged autotransfusion during ECMO decannulation not only effectively maintained Hb levels but also reduced the requirement for allogeneic RBC transfusions. In addition, this approach decreased the associated costs and did not increase the risk of clinical adverse events.

Development of a machine learning approach for prediction of red blood cell transfusion in patients undergoing Cesarean section at a single institution.

Despite recent advances in surgical techniques and perinatal management in obstetrics for reducing intraoperative bleeding, blood transfusion may occur during a cesarean section (CS). This study aims to identify machine learning models with an optimal diagnostic performance for intraoperative transfusion prediction in parturients undergoing a CS. Additionally, to address model performance degradation due to data imbalance, this study further investigated the variation in predictive model performance depending on the ratio of event to non-event data (1:1, 1:2, 1:3, and 1:4 model datasets and raw data).The area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC) were evaluated to compare the predictive accuracy of different machine learning algorithms, including XGBoost, K-nearest neighbor, decision tree, support vector machine, multilayer perceptron, logistic regression, random forest, and deep neural network. We compared the predictive performance of eight prediction algorithms that were applied to five types of datasets. The intraoperative transfusion in maternal CS was 7.2% (1020/14,254). XGBoost showed the highest AUROC (0.8257) and AUPRC (0.4825) among the models. The most significant predictors for transfusion in maternal CS as per machine learning models were placenta previa totalis, haemoglobin, placenta previa partialis, and platelets. In all eight prediction algorithms, the change in predictive performance based on the AUROC and AUPRC according to the resampling ratio was insignificant. The XGBoost algorithm exhibited optimal performance for predicting intraoperative transfusion. Data balancing techniques employed to alter the event data composition ratio of the training data failed to improve the performance of the prediction model.

Implementation of a Standardized Red Blood Cell Transfusion Policy in a Level IV Neonatal Intensive Care Unit: A Quality Improvement Project.

BACKGROUND: Within the neonatal intensive care unit (NICU), infants frequently receive packed red blood cell (PRBC) transfusions. Although medically necessary, potential negative long- and short-term outcomes exist following PRBC transfusions in very low birth-weight (VLBW) infants (<1500 g). Synthesis of the literature demonstrates that the use of a restrictive PRBC transfusion policy can lead to a decreased number of transfusions administered with no increase in long-term neurodevelopmental outcomes. Blood transfusions have also been linked to the diagnosis of necrotizing enterocolitis (NEC) or intraventricular hemorrhage (IVH) in VLBW infants. PURPOSE: For this quality improvement project, a restrictive PRBC transfusion policy was implemented in a level IV NICU to promote consistent care and evaluate changes in PRBC administration. METHODS: The data were collected both pre- and post-policy implementation including: the number of blood transfusions, diagnosis of NEC, and diagnosis of IVH among infants <1500 g. RESULTS: The data showed no significant change in the number of PRBC transfusions administered. Likewise, few infants were diagnosed with NEC or IVH during this same time period with minimal change between pre- and post-policy implementation data. IMPLICATIONS FOR PRACTICE AND RESEARCH: Following policy implementation, there was a significant improvement in communication among providers regarding transfusion ordering and the inclusion of hematocrit thresholds in daily progress notes. This unintended outcome has helped to promote sustainability and enhance patient care within the NICU where this policy was implemented. Continued data collection may be beneficial in indicating whether a standardized PRBC transfusion policy will impact the administration of transfusions and diagnosis of NEC or IVH.

Investigation of the efficacy and safety of wild- type and triple-gene knockout pig RBC transfusions in nonhuman primates.

Introduction: Decreasing rates of blood donation and close margins between blood supply and demand pose challenges in healthcare. Genetically engineered pig red blood cells (pRBCs) have been explored as alternatives to human RBCs for transfusion, and triple-gene knockout (TKO) modification improves the compatibility of pRBCs with human blood in vitro. In this study, we assessed the efficacy and risks of transfusing wild-type (WT)- and TKO-pRBCs into nonhuman primates (NHPs). Methods: Blood from O-type WT and TKO pigs was processed to produce pRBCs for transfusion, which were transfused or not into NHPs (n=4 per group: WT, TKO, and control) after 25% total blood volume withdrawal: their biological responses were compared. Hematological, biochemical, and immunological parameters were measured before, immediately after, and at intervals following transfusion. Two months later, a second transfusion was performed in three NHPs of the transfusion group. Results: Transfusion of both WT- and TKO-pRBCs significantly improved RBC counts, hematocrit, and hemoglobin levels up to the first day post-transfusion, compared to the controls. The transfusion groups showed instant complement activation and rapid elicitation of anti-pig antibodies, as well as elevated liver enzyme and bilirubin levels post-transfusion. Despite the higher agglutination titers with WT-pRBCs in the pre-transfusion crossmatch, the differences between the WT and TKO groups were not remarkable except for less impairment of liver function in the TKO group. After the second transfusion, more pronounced adverse responses without any hematological gain were observed. Conclusions: WT- and TKO-pRBC transfusions effectively increased hematologic parameters on the first day, with rapid clearance from circulation thereafter. However, pRBC transfusion triggers strong antibody responses, limiting the benefits of the pRBC transfusion and increasing the risk of adverse reactions.

Transfusion strategy trials excluding patients transfused outside the trial study period are more likely to report a trend favoring restrictive strategies: a meta-analysis.

OBJECTIVES: Some large, randomized trials investigating red cell transfusion strategies have significant numbers of transfusions administered outside the trial study period. We sought to investigate the potential impact of this methodological issue. STUDY DESIGN AND SETTING: Meta-analysis of randomized controlled trials (RCTs) comparing liberal vs restrictive transfusion strategies in cardiac surgery and acute myocardial infarction patients. The outcome of interest was 30-day or in-hospital mortality. RESULTS: In cardiac surgery, the pooled risk ratio for mortality was 0.83 (95% confidence interval [CI] 0.62-1.12, P = .22) times lower in the restrictive group when compared to the liberal group in trials applying a transfusion strategy throughout the patient's entire perioperative period, and 1.33 (95% CI 0.84-2.11, P = .22) times higher in the restrictive group in trials not applying transfusion strategies throughout the entire perioperative period. When combined, the risk ratio for mortality was 0.98 (95% CI 0.73-1.32, P = .89). In patients with acute myocardial infarction, the risk ratio for mortality was 0.72 (95% CI 0.40-1.28, P = .26) times lower in the restrictive group when compared to the liberal group in 1 trial excluding patients administered the intervention prerandomization and 1.19 (95% CI 0.96-1.47, P = .11) times higher in the restrictive group in 1 trial including patients receiving the intervention prerandomization. When combined the risk ratio for mortality was 1.00 (0.62-1.59, P = .99). CONCLUSION: Though not statistically significant, there was a consistent difference in trends between RCTs administering significant numbers of transfusion outside the trial study period compared to those that did not. The implications of our results may extend to RCTs in other settings that ignore if and how frequently an investigated therapy is administered outside the trial window.

Haemoglobin values, transfusion practices, and long-term outcomes in critically ill patients with traumatic brain injury: a secondary analysis of CENTER-TBI.

Haemoglobin (Hb) thresholds and red blood cells (RBC) transfusion strategies in traumatic brain injury (TBI) are controversial. Our objective was to assess the association of Hb values with long-term outcomes in critically ill TBI patients. We conducted a secondary analysis of CENTER-TBI, a large multicentre, prospective, observational study of European TBI patients. All patients admitted to the Intensive Care Unit (ICU) with available haemoglobin data on admission and during the first week were included. During the first seven days, daily lowest haemoglobin values were considered either a continous variable or categorised as < 7.5 g/dL, between 7.5-9.5 and > 9.5 g/dL. Anaemia was defined as haemoglobin value < 9.5 g/dL. Transfusion practices were described as "restrictive" or "liberal" based on haemoglobin values before transfusion (e.g. < 7.5 g/dL or 7.5-9.5 g/dL). Our primary outcome was the Glasgow outcome scale extended (GOSE) at six months, defined as being unfavourable when < 5. Of 1590 included, 1231 had haemoglobin values available on admission. A mean Injury Severity Score (ISS) of 33 (SD 16), isolated TBI in 502 (40.7%) and a mean Hb value at ICU admission of 12.6 (SD 2.2) g/dL was observed. 121 (9.8%) patients had Hb < 9.5 g/dL, of whom 15 (1.2%) had Hb < 7.5 g/dL. 292 (18.4%) received at least one RBC transfusion with a median haemoglobin value before transfusion of 8.4 (IQR 7.7-8.5) g/dL. Considerable heterogeneity regarding threshold transfusion was observed among centres. In the multivariable logistic regression analysis, the increase of haemoglobin value was independently associated with the decrease in the occurrence of unfavourable neurological outcomes (OR 0.78; 95% CI 0.70-0.87). Congruous results were observed in patients with the lowest haemoglobin values within the first 7 days < 7.5 g/dL (OR 2.09; 95% CI 1.15-3.81) and those between 7.5 and 9.5 g/dL (OR 1.61; 95% CI 1.07-2.42) compared to haemoglobin values > 9.5 g/dL. Results were consistent when considering mortality at 6 months as an outcome. The increase of hemoglobin value was associated with the decrease of mortality (OR 0.88; 95% CI 0.76-1.00); haemoglobin values less than 7.5 g/dL was associated with an increase of mortality (OR 3.21; 95% CI 1.59-6.49). Anaemia was independently associated with long-term unfavourable neurological outcomes and mortality in critically ill TBI patients.Trial registration: CENTER-TBI is registered at ClinicalTrials.gov, NCT02210221, last update 2022-11-07.

Oxygen Extraction Ratios to Guide Red Blood Cell Transfusion.

Hemoglobin-based red blood cell transfusion (RBC) triggers do not clearly identify which patients with moderate anemia (hemoglobin 7-10 g/dL) will benefit from RBC transfusion. The National Heart, Lung, and Blood Institute has recognized the need for bedside oxygenation measures to enhance transfusion decision-making. This narrative review uses four studies to explore the potential of the oxygen extraction ratio (O2ER)-the ratio of consumed oxygen to delivered oxygen in a critical tissue bed as a more physiologically relevant indicator for guiding RBC transfusions in patients with moderate anemia. The aim of this review is to present existing data on the relationship between O2ER and responsiveness to RBC transfusion, as well as the feasibility of O2ER as bedside measure of tissue oxygenation. This review presents a narrative appraisal of three critical papers that investigate the relationship between O2ER and transfusion outcomes, and one paper that demonstrates proof-of-concept for a noninvasive device to measure O2ER at the bedside. Despite limitations in the existing studies, including small sample sizes and observational designs, the evidence collectively suggests that O2ER has the potential to enhance transfusion decision accuracy. The development of noninvasive measurement devices could facilitate widespread implementation in many kinds of care settings.

Acute normovolemic hemodilution in cardiac surgery: Rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 ml as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

Clinical prediction model for red cell blood transfusion in elective primary posterior lumbar spine fusion.

Overestimated the cross-match of preoperative PRC preparation for elective primary lumbar spinal fusion needs revision for cost-effectiveness. We aimed to develop a novel preoperative predictive model for appropriate PRC preparation. This clinical prediction model in a retrospective cohort was studied between January 2015 and September 2022. Multivariate logistic regression models were used to assess predictive variables. The logistic coefficient of each predictor generated scores to establish a predictive model. The area under the receiver operating characteristic curve (AuROC) was used to evaluate the model. The predictive performance was validated using bootstrapping techniques and externally validated in 102 independent cases. Among 416 patients, 178 (43%) required transfusion. Four final predictors: preoperative hematocrit level, laminectomy level, transforaminal lumbar interbody fusion level, and sacral fusion. When categorized into two risk groups, the positive predictive values for the low-risk score (≤ 4) were 18.4 (95% Cl 13.9, 23.6) and 83.9 (95% CI 77.1, 89.3) for the high-risk score (> 4). AuROC was 0.90. Internal validation (bootstrap shrinkage = 0.993) and external validation (AuROC: 0.91). A new model demonstrated exemplary performance and discrimination in predicting the appropriate preparation for PRC. This study should be corroborated by rigorous external validation in other hospitals and by prospective assessments.

Clinical Practice Guideline for Red Blood Cell Transfusion Thresholds in Very Preterm Neonates.

Importance: Red blood cell (RBC) transfusion is a common medical intervention to treat anemia in very preterm neonates; however, best transfusion practices, such as thresholds, remain uncertain. Objective: To develop recommendations for clinicians on the use of RBC transfusions in very preterm neonates. Evidence Review: An international steering committee reviewed evidence from a systematic review of 6 randomized clinical trials (RCTs) that compared high vs low hemoglobin-based or hematocrit-based transfusion thresholds. The steering committee reached consensus on certainty-of-evidence ratings and worked with a panel from stakeholder organizations on reviewing the evidence. With input from parent representatives and the stakeholder panel, the steering committee used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to develop recommendations. Findings: A systematic review of 6 RCTs encompassing 3483 participants (1759 females [51.3%]; mean [SD] age range, 25.9-29.8 [1.5-3.0] weeks) was used as the basis of the recommendations. The ranges for higher hemoglobin concentration (liberal) vs lower hemoglobin concentration (restrictive) threshold study arms were similar across the trials. However, specific thresholds differed based on the severity of illness, which was defined using variable criteria in the trials. There was moderate certainty of evidence that low transfusion thresholds likely had little to no difference in important short-term and long-term outcomes. The recommended hemoglobin thresholds varied on the basis of postnatal week and respiratory support needs. At postnatal weeks 1, 2, and 3 or more, for neonates on respiratory support, the recommended thresholds were 11, 10, and 9 g/dL, respectively; for neonates on no or minimal respiratory support, the recommended thresholds were 10, 8.5, and 7 g/dL, respectively (to convert hemoglobin to grams per liter, multiply by 10.0). Conclusions and Relevance: This consensus statement recommends a restrictive RBC transfusion strategy, with moderate certainty of evidence, for preterm neonates with less than 30 weeks' gestation.

Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

Serum Ferritin Levels in Very Preterm Infants Receiving Erythrocyte Transfusions: A Retrospective Study.

Very preterm infants often need red blood cell transfusions (RBCT) during intensive care and are at risk of iron overload. This study reviewed the records of 65 very preterm neonates who required at least one RBCT to ascertain the iron status using serum ferritin levels at 4-6 weeks age before oral iron was commenced. High serum ferritin level was found in 52.3% (n = 34) neonates. Need for > 1RBCT was significantly and independently associated with iron excess (P < 0.001). Increased ferritin noted following transfusions in neonatal period can have implications for determining the appropriate time for starting iron supplementation in this subgroup of neonates.

Management Considerations for Air Medical Transport Programs Transfusing RhD-Positive Red Blood Cell-Containing Products to Females of Childbearing Potential.

Recent years have seen increased discussion surrounding the benefits of damage control resuscitation, prehospital transfusion (PHT) of blood products, and the use of whole blood over component therapy. Concurrent shortages of blood products with the desire to provide PHT during air medical transport have prompted reconsideration of the traditional approach of administering RhD-negative red cell-containing blood products first-line to females of childbearing potential (FCPs). Given that only 7% of the US population has blood type O negative and 38% has O positive, some programs may be limited to offering RhD-positive blood products to FCPs. Adopting the practice of giving RhD-positive blood products first-line to FCPs extends the benefits of PHT to such patients, but this practice does incur the risk of future hemolytic disease of the fetus and newborn (HDFN). Although the risk of future fetal mortality after an RhD-incompatible transfusion is estimated to be low in the setting of acute hemorrhage, the number of FCPs who are affected by this disease will increase as more air medical transport programs adopt this practice. The process of monitoring and managing HDFN can also be time intensive and costly regardless of the rates of fetal mortality. Air medical transport programs planning on performing PHT of RhD-positive red cell-containing products to FCPs should have a basic understanding of the pathophysiology, prevention, and management of hemolytic disease of the newborn before introducing this practice. Programs should additionally ensure there is a reliable process to notify receiving centers of potentially RhD-incompatible PHT because alloimmunization prophylaxis is time sensitive. Facilities receiving patients who have had PHT must be prepared to identify, counsel, and offer alloimmunization prophylaxis to these patients. This review aims to provide air medical transport professionals with an understanding of the pathophysiology and management of HDFN and provide a template for the early management of FCPs who have received an RhD-positive red cell-containing PHT. This review also covers the initial workup and long-term anticipatory guidance that receiving trauma centers must provide to FCPs who have received RhD-positive red cell-containing PHT.