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Key Points

  • Low-titer group O whole blood (LTOWB) has reemerged as a valuable option for the treatment of life-threatening hemorrhage in the pediatric population.
  • LTOWB provides balanced hemostatic resuscitation, reduces donor exposures, and simplifies logistics.
  • Evidence from pediatric trauma studies demonstrates that LTOWB is safe, feasible, and associated with reduced early mortality compared to traditional component therapy.
  • While pediatric-specific randomized trials remain limited, the current literature supports the use of LTOWB as a first-line resuscitative product in hemorrhagic shock. Ongoing patient blood management integration and data collection will further define its optimal use in children.

Introduction

  • Whole blood is composed of packed red blood cells, which determine the ABO and Rh blood type, and plasma, which contains antibodies against the absent ABO antigens, and platelets.
  • A donor with group A red cells will have anti B antibodies in the plasma, while a group B red cell donor will have anti-A antibodies.
  • Group O red cell donors are considered universal for red cell transfusion, as they have both anti-A and anti-B antibodies in their plasma (Table 1).
  • The Rh antigen differs in that anti-Rh antibodies are not naturally present; they develop only when an Rh-negative recipient is exposed to Rh-positive blood. Thus, an Rh-negative donor does not carry anti-Rh antibodies in plasma, unlike the anti-B antibodies found in type A donors. Consequently, the universal donor for packed red cells is type O Rh negative, and the universal plasma donor is type AB Rh negative. In contrast, there is no universal donor for whole blood.
  • For additional information, please refer to the OpenAnesthesia summary: ABCs of Blood Transfusions. Link

Table 1. Blood type as determined by antigens present on red blood cells and the corresponding antibodies present in the plasma.

Merits of Whole Blood

  • Pediatric trauma patients requiring massive transfusion protocols (MTPs) had reduced early mortality and comparable safety when resuscitated with LTOWB (see below for more details) compared with traditional component therapy.1
  • Additionally, whole blood resuscitation simplifies MTPs and may improve early hemostatic control compared with component therapy.2
  • Whole blood is advantageous for several reasons, as mentioned in the table below.3

Table 2. Advantages of whole blood

  • The Pediatric Traumatic Hemorrhagic Shock Consensus Conference suggests the use of low-titer, group O whole blood in pediatric trauma patients with hemorrhagic shock.3 While whole blood offers many advantages over individual component therapy, it is important to remember that group O whole blood can still place non-group O recipients at risk for hemolysis due to donor anti-A or anti-B antibodies, depending on the blood type. To reduce this risk, low-titer (≤256 anti-A, anti-B antibodies) group O whole blood is used.
  • Please see the OA summary on whole blood transfusions for more details. Link

Leukocyte Reduction

  • Leukocyte-reduced LTOWB may further enhance safety by reducing febrile nonhemolytic reactions and minimizing the risk of cytomegalovirus transmission.
  • Although leukoreduction can slightly reduce platelet yield, current evidence suggests minimal impact on hemostatic efficacy.2 Most transfusion services utilize prestorage leukoreduction, preserving platelet function while adhering to pediatric Patient Blood Management (PBM) principles and Association for the Advancement of Blood and Biotherapies standards.

Table 3. Summary of the characteristics and advantages of LTOWB. Adapted from OA summary on whole blood transfusions. https://www.openanesthesia.org/keywords/whole-blood-transfusions/
*In one pediatric study, the median time to transfuse a unit of whole blood was 15 minutes, compared with 303 minutes to administer one unit each of red blood cells, plasma, and platelets.1

Pediatric Indications

  • LTOWB is increasingly being used in pediatric resuscitation due to its balanced composition and logistical advantages.
  • LTOWB can be used in pediatric trauma resuscitation up to 40mL/kg. One case report describes 80ml/kg of LTOWB administered to a neonate for massive hemorrhage secondary to trauma.5
  • Type-specific, cross-matched whole blood has also been used in elective craniofacial, congenital cardiac, and complex spine surgery.
  • In a retrospective study of pediatric craniofacial surgery, patients who received type-specific whole blood had less donor exposure and reduced intraoperative blood loss compared with those who received reconstituted blood (packed red cells and fresh-frozen plasma from the same donor in a 1:1 ratio.6
  • In a prospective study of pediatric spine surgery, patients who received whole blood had a shorter intensive care unit (ICU) stay and a reduced inflammatory response compared with those who received component therapy in a 1:1:1 ratio.7
  • LTOWB has been used for hemorrhage from medical causes, including gastrointestinal bleeding, menorrhagia, and severe anemia, at some tertiary care pediatric centers.8
  • Pre-hospital Use: A city in Texas authorizes first responders to administer LTOWB to pediatric patients at the point of injury, in the field, when specific criteria are met:
    • Systolic blood pressure (SBP) less than 70mmHg, or
    • SBP less than 90 mmHg AND heart rate above 110 beats per minute
    • End-tidal CO2 less than 25 mmHg, or
    • Witnessed cardiac arrest less than 5 minutes with continuous cardiopulmonary resuscitation being provided.6
  • When these criteria are met, first responders may administer 500 mL of whole blood to children aged 6-10 years, and 1000 mL to patients aged 11-13 years and older.9

Figure 1. Whole blood components in a 500 mL bag. Adapted from OA Summary on whole blood transfusions https://www.openanesthesia.org/keywords/whole-blood-transfusions/

Outcomes

  • LTOWB provides hemostatic outcomes that are equivalent to, and in some cases superior to, those achieved with balanced component therapy.
  • LTOWB transfusion is associated with decreased total product volume and earlier resolution of shock.2
  • Studies show shorter time to first transfusion, rapid correction of coagulopathy, and faster improvement in base deficit.4
  • Children receiving LTOWB required fewer total transfusion episodes and achieved quicker normalization of coagulation parameters.9
  • Across available studies, LTOWB has demonstrated consistent safety, with no increased risk of transfusion-related adverse events, including hemolysis or alloimmunization.4
  • The use of typed and cross-matched whole blood in selective, elective surgeries has been associated with reduced donor exposure, decreased blood loss, shorter ICU stays, and lower inflammatory response.

Pitfalls: Hemolysis

  • Concerns regarding hemolytic reactions with LTOWB have been mitigated by adopting low anti-A and anti-B titer thresholds.
  • No clinically significant hemolytic events have been reported following LTOWB transfusion in children.2,4
  • Surveillance protocols, including direct antiglobulin testing and hemolysis panels, have confirmed the rarity of immune-mediated complications in well-screened LTOWB inventories.

PBM Integration

  • The integration of LTOWB into pediatric PBM programs focuses on minimizing unnecessary transfusions, optimizing hemostatic balance, and reducing donor exposures.
  • Key PBM considerations include:
    • Protocol standardization: Establishing clear criteria for LTOWB use within pediatric MTPs.
    • Inventory management: Shelf life typically limited to 14 days; close coordination with adult trauma services helps prevent wastage.
    • Team education: Simulation and competency training improve activation speed and transfusion accuracy.
    • Data tracking: Continuous quality improvement through monitoring transfusion volume, product age, and outcomes.
    • As summarized in PBM literature, LTOWB aligns with PBM principles by maximizing transfusion efficiency and conserving blood resources.

References

  1. Campwala I, Dorken-Gallastegi A, Spinella PC et al. Whole blood to total transfusion volume ratio in injured children: A national database analysis. J Trauma Acute Care Surg. 2025;98(2):287-94. PubMed
  2. Fisher, A.D. The use of low-titer group O whole blood for TEMS. Tactical and Law Enforcement Medicine Newsroom, American College of Emergency Physicians. 2019. Accessed on November 26th, 2025 Link
  3. Russell RT, Esparaz JR, Beckwith MA, et al. Pediatric traumatic hemorrhagic shock consensus conference recommendations. J Trauma Acute Care Surg. 2023;94(1S Suppl 1): S2-S10. PubMed
  4. Gaines BA, Yazer MH, Triulzi DJ, et al. Low-titer group O whole blood in injured children requiring massive transfusion. Annals of Surgery. 2023; 277(4): e919–e924. PubMed
  5. Green RW, Cotton BA. Neonatal trauma resuscitation: Successful use of low-titer O+ whole blood in a 4-day-old infant with hemorrhagic shock. Transfusion. 2025;65:S181-S184. PubMed
  6. Thottathil P, Sesok-Pizzini D, Taylor JA, et al. Whole blood in pediatric craniofacial reconstruction surgery. J Craniofac Surg. 2017;28(5):1175–8. PubMed
  7. Vasan PK, Rajasekaran S, Viswanathan VK et al. Is fresh, leucodepleted, whole blood transfusion superior to blood component transfusion in pediatric patients under-going spinal deformity surgeries? A prospective, randomized study analyzing postoperative serological parameters and clinical recovery. Eur Spine J. 2021;30(7):1943–9. PubMed
  8. Gaines BA, Yazer MH, Triulzi DJ, et al. Low-titer group O whole blood in injured children requiring massive transfusion. Annals of Surgery. 2023; 277(4): e919–e924. PubMed
  9. Leeper CM, Yazer MH, Triulzi et al. Whole blood is superior to component transfusion for injured children: A propensity-matched analysis. Ann Surg. 2020;272(4):590-4. PubMed