Authors: Miriam Brown (Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Deva Sharma (Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Kaycie Atchison (Quality, Safety, & Risk Prevention, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Bradley M. Dennis (Division of Acute Care Surgery, Department of Surgery, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Erika Hall (Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Angela Mueller (Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Christine Schaeffer (Division of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Jessica E. Schucht (Division of Acute Care Surgery, Department of Surgery, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Jill R. Streams (Division of Acute Care Surgery, Department of Surgery, Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Toufik Tahiri (Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Garrett S. Booth (Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA), Jeremy W. Jacobs (Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA)
Categories: Case Report, blood type, immunohematology (RBC serology, blood groups), RBC transfusion, transfusion complications—noninfectious, trauma, whole blood
Source: Transfusion
Doi: 10.1111/trf.18268
Incorrect blood typing and mis‐transfusion due to low‐titer group O whole blood resuscitation
Authors: Miriam Brown, Deva Sharma, Kaycie Atchison, Bradley M. Dennis, Erika Hall, Angela Mueller, Christine Schaeffer, Jessica E. Schucht, Jill R. Streams, Toufik Tahiri, Garrett S. Booth, Jeremy W. Jacobs
Abstract
Background
Resuscitation strategies for massive hemorrhage increasingly involve the use of low‐titer group O whole blood (LTOWB) due to evidence suggesting improved patient outcomes. However, the potential risk of incorrect ABO typing following LTOWB administration, possibly leading to mis‐transfusion, remains insufficiently explored. This case series aims to highlight the potential risk of ABO mistyping associated with LTOWB transfusions in trauma settings.
Study Design and Methods
We retrospectively reviewed three cases involving trauma patients who received LTOWB transfusions at a high‐volume urban Level 1 Trauma Center. ABO and RhD typing were performed using automated column agglutination technology (Ortho ID‐MTS™), and discordant typing results prompted further investigations to confirm patients' true ABO type and identify mis‐transfusions.
Results
All three patients initially received LTOWB due to traumatic hemorrhage. Initial ABO typing after LTOWB administration incorrectly identified the patients as group O. Follow‐up investigations later confirmed their true blood types as group A. Two cases resulted in subsequent inadvertent transfusions of ABO‐incompatible plasma. Although no severe adverse clinical outcomes occurred, these events were reported to regulatory bodies as biologic product deviations.
Discussion
Our findings highlight a rare but clinically significant risk of ABO typing errors following LTOWB transfusion, primarily due to contamination of patient samples with donor blood. Such errors carry the potential for acute hemolytic reactions, underscoring the critical need for strict adherence to sampling protocols. Whenever possible, ABO typing should be performed prior to LTOWB administration, and samples should be drawn from a site contralateral to the transfusion.
INTRODUCTION
Resuscitation strategies for massive hemorrhage are rapidly evolving, with a growing number of centers across the United States adopting low‐titer group O whole blood (LTOWB)—collected from donors with low‐titer anti‐A and anti‐B antibodies—into massive transfusion protocols and pre‐hospital care. ^1^ , ^2^ , ^3^ This shift is largely driven by emerging evidence from both military ^4^ , ^5^ and civilian trauma settings ^6^ , ^7^ , ^8^ suggesting that LTOWB may offer a survival advantage over conventional component‐based transfusion.
Despite its potential advantages, LTOWB introduces important challenges, including the risk of inaccurate ABO blood typing in patients who receive ABO compatible but non‐ABO type‐specific blood (e.g., group O blood transfused to a group A recipient). Although ABO typing inaccuracies can occur with component‐based transfusions, ^9^ this risk, at least theoretically, may be heightened with LTOWB. This increased risk stems from a potentially lower likelihood of detecting ABO discrepancies (discordance between forward and reverse grouping) following LTOWB administration compared to component therapy, where patients receive group O red blood cells (RBCs) and group A or AB plasma.
Accurate ABO typing is crucial for ensuring transfusion safety and efficacy. ^10^ Errors in blood typing can lead to severe clinical consequences, including transfusion delays and mis‐transfusion, resulting in acute hemolytic reactions and death. ^11^ Despite advancements in serological testing techniques and rigorous adherence to transfusion protocols, ABO typing inaccuracies remain a concern, ^12^ , ^13^ particularly among patients who have recently undergone large volume or massive transfusion.
In this case series, we describe three patients in whom the administration of LTOWB was temporally associated with ABO mistyping, including two cases where subsequent ABO‐incompatible plasma transfusions transpired based on inaccurate ABO typing results. Our goal is to raise awareness among healthcare professionals regarding ABO mistyping during trauma resuscitation, particularly when LTOWB is used, and provide guidance on essential diagnostic and management considerations for clinicians involved in administering LTOWB.
CASE PRESENTATIONS
Methods
In all three cases, ABO and RhD typing were performed via automated column agglutination technology on the Ortho VISION™ Analyzer (QuidelOrtho, Raritan, NJ) using MTS™ A/B/D Monoclonal and Reverse Grouping Cards (Micro Typing Systems, Inc., Pompano Beach, FL). Both the institutional blood bank protocol and Association for the Advancement of Blood and Biotherapies (AABB) standards mandate that the current testing interpretation match the historic typing, if available. ^14^ If historical data are unavailable, a second independent specimen must be obtained and analyzed before ABO type‐specific transfusion. Any discrepancy between current and historical ABO/Rh typing results and/or interpretations requires investigation.
Case 1
A 47‐year‐old female arrived as a Level 1 trauma after being found unconscious with a deep scalp laceration and an estimated blood loss of 500–600 mL at the scene. Upon arrival, she was hypothermic and hypotensive, prompting the rapid transfusion of 2 units of RhD‐negative LTOWB. Concurrent laboratory testing included type and screen, complete blood count (CBC), basic metabolic profile (BMP), prothrombin time (PT), and activated partial thromboplastin time (aPTT) (Tables 1 and 2). As this was the patient's first ABO type performed at our institution, an ABO confirmation was drawn per protocol.
Both the initial ABO type and the confirmation type resulted as O RhD‐negative (Table 1). The patient underwent surgical intervention for wound washout and closure, during which she experienced approximately 1 L of additional blood loss. She subsequently received 1 unit of O RhD‐negative RBCs and 1 unit of O RhD‐positive plasma approximately 6 h post‐LTOWB transfusion. She was discharged the next day in stable condition.
Approximately 2 weeks later, the patient returned to the emergency department (ED) with signs of a possible wound infection. Repeat ABO typing unexpectedly resulted in a mixed field reaction with anti‐A (though interpreted as A RhD‐positive), prompting a wrong‐blood‐in‐tube (WBIT) investigation by the blood bank. Confirmatory repeat testing affirmed her blood type as A RhD‐positive, identifying the previous transfusion of O RhD‐positive plasma as ABO‐incompatible. This event was reported to the US Food and Drug Administration (FDA) as a biologic product deviation (BPD) ^15^ , ^16^ ; however, there was no reported clinical or laboratory evidence of hemolysis or other adverse effects related to the incompatible transfusion.
Case 2
A 67‐year‐old female was transferred from a referring institution as a Level 1 trauma after sustaining head trauma from a fall, complicated by a pulseless electrical activity (PEA) arrest with subsequent return of spontaneous circulation (ROSC). During transport, she received 1 unit of O RhD‐negative RBCs and 1 unit of group A liquid plasma. Upon arrival, the patient was intubated, tachycardic, and persistently hypotensive despite vasopressor therapy. She received 2 units of RhD‐positive LTOWB approximately 1 h after the initial transfusions. Standard trauma laboratory tests, including ABO blood type and antibody screen, CBC, BMP, and PT/aPTT, were obtained upon arrival (Tables 1 and 2).
Initial ABO/RhD typing resulted as O RhD‐positive, conflicting with historical typing obtained 7 years prior (A RhD‐positive). Suspecting a possible WBIT event, repeat ABO typing was performed approximately 1 h later, demonstrating a mixed field reaction with anti‐A (interpreted as A RhD‐positive). No incompatible blood products were administered, and no clinical complications ensued.
Case 3
A 66‐year‐old male was airlifted following severe trauma resulting from a motor vehicle collision. During transport, he received 2 units of O RhD‐negative RBCs and 2 units of group A liquid plasma. Upon arrival approximately 1 h later, 1 unit of RhD‐positive LTOWB was administered for persistent hypotension. Concurrently, a type and screen, ABO confirmation, CBC, and PT/aPTT were drawn (Tables 1 and 2). Imaging revealed multiple fractures, a subdural hematoma, hemopneumothorax, and a splenic laceration.
The type and screen resulted as O RhD‐positive with a negative antibody screen. He underwent emergency interventions and received 1 unit of group O plasma approximately 30 min after the LTOWB administration.
The patient remained hospitalized but clinically stable without significant bleeding; therefore, a repeat type and screen was not obtained until 12 days later, when his hemoglobin declined to near the transfusion threshold of 7 g/dL. This repeat testing identified his blood type as A RhD‐positive, which was subsequently confirmed. Retrospective review revealed that he had received an incompatible plasma transfusion (1 unit of O RhD‐positive plasma), which was reported to the FDA via a BPD report. No immediate clinical complications were observed. Antibody screening also identified an anti‐Jk^a^ alloantibody, and serologic phenotyping of segments from the three previously transfused units showed that all expressed the Jk^a^ antigen. Additional testing demonstrated a negative direct antiglobulin test and no mixed‐field agglutination on ABO typing, suggesting possible clearance of the Jk^a^‐positive donor cells. Although lactate dehydrogenase was elevated, total bilirubin and haptoglobin remained within normal limits. Thus, it remains unclear if this represented a delayed serologic or hemolytic transfusion reaction.
DISCUSSION
The cases presented in this series highlight important clinical and laboratory challenges associated with ABO typing inaccuracies following the administration of LTOWB during trauma resuscitation. Although LTOWB offers benefits—including rapid deployment, simplified logistics in austere and pre‐hospital environments, and potential improvements in patient outcomes and survival—these cases underscore an important risk with respect to ABO mistyping that could potentially result in inadvertent transfusion of ABO‐incompatible blood products.
Obtaining a type and screen during active resuscitation with universal blood products carries a risk of producing ABO typing results that do not accurately reflect the recipient's true blood type. This issue arises primarily when blood samples are drawn during or shortly after transfusion—particularly from infusion lines or sites immediately downstream of transfusion—due to contamination with donor blood. This limitation applies regardless of whether resuscitation involves component therapy or LTOWB.
However, our findings suggest a potentially greater challenge with LTOWB: its use may reduce the likelihood of detecting ABO discrepancies that could otherwise alert clinicians and medical technologists to inaccurate typing. Because LTOWB contains ABO‐identical red cells and plasma from a single group O donor, it inherently minimizes forward and reverse grouping mismatches. As a result, a sample composed entirely of transfused LTOWB may appear concordant, reflecting the donor's (i.e., group O) type while masking the patient's true ABO type (Figure 1). In contrast, component‐based transfusions—such as group O red cells with group A or AB plasma—often produce detectable discrepancies (e.g., forward grouping as O and reverse grouping with absent or altered isoagglutinins), which can prompt further investigation. Furthermore, although automated typing methods enable rapid and efficient testing, some platforms may be less sensitive to mixed‐field reactions due to sampling techniques, potentially compounding the risk of inaccurate results. ^17^
![FIGURE 1: Schematic depicting the possible ABO forward and reverse grouping results for patients receiving universal ABO compatible individual component therapy and low‐titer group O whole blood (LTOWB). Given the different ABO type of the red blood cells and plasma used in component therapy, there may be a higher likelihood of detecting a forward and reverse group discrepancy compared to the use of LTOWB wherein the red blood cells and plasma are the same ABO type. Created in https://BioRender.com. [Color figure can be viewed at wileyonlinelibrary.com]](TRF-65-1203-g001.jpg)
To address these risks systematically, we propose the following Samples for ABO typing should ideally be collected before the administration of LTOWB. If pre‐transfusion sampling is not feasible due to emergent clinical needs, specimens should be collected at least 15 min after completion of the transfusion, ensuring adequate flushing of the line to minimize donor blood contamination.Alternative vascular access sites should be utilized for sample collection, ideally on the contralateral side or from peripheral access sites, to reduce the likelihood of sample contamination with donor blood.If ABO typing cannot be obtained prior to LTOWB administration and historical ABO typing results are unavailable, typing should be repeated only when there is confidence that enough of the patient's own cells/plasma are present. In the interim, the ABO type should be considered preliminary or “indeterminate.” Although there are no standardized guidelines, we propose that definitive ABO typing should be postponed for at least 24–48 h post‐transfusion to allow for the mixing of donor and recipient blood.In the intervening time period until resolution of ABO blood typing, use of universal donor RBCs (group O) and universal donor plasma (group AB or potentially group A) should be employed.Enhanced education and targeted training should be provided for clinical and laboratory staff, emphasizing the importance of proper specimen collection techniques, awareness of potential ABO discrepancies, and vigilant monitoring in trauma resuscitation scenarios.
Although none of the patients in this series experienced acute hemolysis or other severe clinical consequences from their ABO‐incompatible transfusions, the potential for significant harm—including acute hemolytic transfusion reactions—remains an important safety concern. ^12^ , ^18^ The National Quality Forum describes a serious adverse event or a “never event” as “patient death or serious injury associated with unsafe administration of blood products.” ^19^ While no deaths or serious injury occurred, these near misses underscore the need for increased vigilance and proactive management of ABO typing accuracy, particularly in settings involving massive transfusions with LTOWB. As observed, these inaccuracies can result in inappropriate transfusion decisions, posing serious patient safety risks. The described incidents emphasize the need for education and standardized specimen collection procedures, especially during massive transfusion scenarios.
In conclusion, while LTOWB offers advantages in trauma resuscitation, meticulous adherence to ABO typing protocols and specimen collection procedures remains critical to minimizing transfusion‐related risks, particularly ABO misidentification and mis‐transfusion. The implementation of standardized guidelines, coupled with ongoing education of clinical and laboratory personnel, is essential to ensuring transfusion safety and optimizing patient outcomes. Importantly, in the absence of federally mandated post‐marketing surveillance for blood products—unlike other FDA‐regulated therapies—vigilant reporting of adverse events, including those that are unrecognized or underreported, is crucial to advancing the safety and efficacy of transfusion practices.
CONFLICT OF INTEREST STATEMENT
The authors have disclosed no conflicts of interest.