What blood type and crossmatch results are required for a red blood cell transfusion to be considered safe?

Blood Type and Crossmatch Requirements for Safe Red Blood Cell Transfusion

For safe red blood cell transfusion, at minimum you must confirm ABO and RhD compatibility through proper blood typing and crossmatching, but for patients with sickle cell disease or those receiving chronic transfusions, extended antigen matching for Rh (C, E, c, e) and K antigens is mandatory to prevent life-threatening alloimmunization and hemolytic reactions. 1

Minimum Requirements for All Patients

Basic Compatibility Testing

• ABO and RhD typing must be performed on all transfusion recipients before any red cell transfusion 1, 2
• Antibody screening is essential to detect clinically significant unexpected antibodies that could cause hemolytic reactions 3, 4
• Crossmatching verifies compatibility between donor red cells and recipient plasma 5, 3

Crossmatch Methods Based on Antibody Status

• If no unexpected antibodies are detected: An immediate spin crossmatch is acceptable, though it carries a small risk (1 in 250,000) of missing clinically significant antibodies like anti-Jka, anti-Wra, anti-C, anti-c, or anti-Kpa 3
• If unexpected antibodies are present: Full crossmatch including 37°C incubation and indirect antiglobulin test (IAT) is required 4
• Patients without antibodies can have crossmatches performed at the time of issue rather than in advance, improving efficiency 4

Critical Rh Considerations

• All Rh-negative patients must receive Rh-negative blood, particularly women of childbearing potential and children, to prevent alloimmunization and future hemolytic disease of the fetus and newborn 2
• If Rh-positive blood is inadvertently given to an Rh-negative patient, anti-D immunoglobulin must be administered within 72 hours at 20-25 mg per 1 mL of transfused RBCs 2

Enhanced Requirements for High-Risk Populations

Sickle Cell Disease Patients (All Genotypes)

Extended antigen matching is mandatory for all SCD patients, regardless of whether they currently have antibodies, because this population has the highest alloimmunization rate of any transfused group. 1

Minimum Extended Matching Protocol

• Rh antigens: C, c, E, e (not just D) 1
• K antigen (Kell system) 1
• This reduces alloimmunization from approximately 1.94 per 100 units (with ABO/RhD matching alone) to 0.40-0.69 per 100 units 1, 2

Additional Recommended Matching

• Jka/Jkb, Fya/Fyb, S/s antigens provide further protection and should be considered for extended matching 1
• Extended matching can reduce alloimmunization rates to as low as 0.25 per 100 units transfused 1, 2

Special Considerations for SCD

• Blood should be HbS-negative and ideally less than 10 days old for simple transfusion, less than 8 days old for exchange transfusion 1
• Patients with RHDDIIIa-CE(4-7)-D or RHCECeRN alleles (encoding partial C antigen) must receive C-negative red cells to prevent allo-anti-C development 1, 2
• Patients with GATA mutation in ACKR1 gene are not at risk for anti-Fyb and do not require Fyb-negative units 1, 2
• If the patient has been transfused within 28 days, allow minimum 72 hours between group and save specimen and crossmatch for surgery 1

Extended Antigen Profiling Recommendations

Obtain an extended red cell antigen profile (by genotype or serology) at the earliest opportunity, optimally before the first transfusion, for all SCD patients and chronically transfused individuals. 1

Minimum Profile Should Include

• C/c, E/e, K, Jka/Jkb, Fya/Fyb, M/N, and S/s antigens 1
• Genotyping is preferred over serologic phenotyping because it provides higher accuracy for C antigen determination and Fyb matching, remains reliable after recent transfusion, and includes antigens without serologic reagents 1, 2
• Serologic phenotyping may be inaccurate if the patient was transfused within the last 3 months 1

Management of Patients with Existing Alloantibodies

Transfusion Strategy

• Provide red cells that are negative for each antigen corresponding to all identified clinically significant alloantibodies 2
• Continue extended Rh (C/c, E/e) and K matching even when providing antigen-negative units to prevent formation of additional antibodies 2
• The most common antibodies complicating transfusion in SCD are directed against C, E, and K antigens 1, 5

Life-Threatening Situations

When compatible blood cannot be found for a patient with severe, life-threatening anemia:

• Consider adjunctive immunosuppressive therapy (IVIg, steroids, and/or rituximab) to reduce hemolysis risk 1, 2
• Maintain ongoing interdisciplinary discussion between hematology and transfusion medicine teams to balance transfusion benefits against risks 1, 2
• Incorporate shared decision-making with the patient or surrogate regarding risks and benefits 2

Emergency Transfusion Protocols

Uncrossmatched Type O Blood

• Type O red cells can be safely used for emergency resuscitation when immediate transfusion is needed 30-45 minutes before type-specific blood is available 6
• Use O-negative for women of childbearing age (at least 2 units available) 6
• O-positive can be used for men and post-menopausal women 6
• The risk of acute hemolytic reactions with uncrossmatched type O blood is extremely low, and seroconversion rates are lower than previously reported, possibly due to immune suppression from hemorrhagic shock 6

Emergency Surgery in SCD Patients

• If Hb ≥90 g/L and surgical risk is low, proceed to surgery without delay and transfuse intra-operatively or post-operatively if necessary 1
• If Hb is low, provide simple top-up transfusion to target 100 g/L pre-operatively, provided this will not delay surgery 1
• Contact consultant haematologist if any doubt about pre-operative transfusion preparation 1

Common Pitfalls to Avoid

• Never rely solely on ABO/RhD matching for SCD patients or chronically transfused individuals – this population requires mandatory extended matching even without detectable antibodies 1, 2
• Do not assume Rh matching prevents all Rh alloimmunization in SCD – these patients remain at risk for antibodies to RH variants due to genetic diversity 1
• Do not delay RhIG administration beyond 72 hours if Rh-incompatible blood is inadvertently given to an Rh-negative patient 2
• Maintain high suspicion for RH variants in SCD patients who develop Rh antibodies despite receiving Rh-matched transfusions 1
• Do not perform extended antigen typing after recent transfusion – use genotyping instead, as serologic methods will be inaccurate 1

ABO-Incompatible Plasma Considerations

While the question focuses on red cells, be aware that:

• ABO-compatible plasma should be provided whenever available to eliminate hemolysis risk 7
• Pediatric patients have markedly higher risk of clinically significant hemolysis from ABO-incompatible plasma, especially with larger volumes 7
• If incompatible plasma must be used, close clinical monitoring for hemolysis is required 7