Which red blood cell (RBC) unit is least likely to cause alloimmunization in an 18-year-old African-American woman with sickle cell anemia and a phenotype of D+C+c+E-e+; K-k+; Fy(a-b-); Jk(a+b-)?

Option B is the Least Likely to Cause Alloimmunization in This Sickle Cell Patient

The unit with phenotype D+C+c+E+e+; K–k+; Fy(a–b–); Jk(a+b–) (Option B) is the least likely to cause alloimmunization in this patient because it only differs in the E antigen, which is less immunogenic than the K antigen or C antigen mismatches in the other options.

Understanding Antigen Immunogenicity in Sickle Cell Disease

Patients with sickle cell disease have the highest rate of alloimmunization of any transfused patient population 1. When selecting blood units for patients with a history of stroke requiring regular RBC exchanges, preventing alloimmunization is critical to reduce morbidity and mortality.

The patient's phenotype is:

• D+C+c+E–e+; K–k+; Fy(a–b–); Jk(a+b–)

Let's analyze each option by comparing it to the patient's phenotype:

Option A: D+C+c+E–e+; K+k+; Fy(a–b–); Jk(a+b–)

• Mismatch: K antigen (patient is K–, unit is K+)
• K antigen is highly immunogenic (approximately 5-10% of K-negative individuals exposed to K+ blood develop anti-K)
• K antigen mismatch is a major concern in sickle cell patients

Option B: D+C+c+E+e+; K–k+; Fy(a–b–); Jk(a+b–)

• Mismatch: E antigen (patient is E–, unit is E+)
• E antigen is less immunogenic than K
• The ASH guidelines specifically mention that E antigen matching is important but ranks below K in immunogenicity

Option D: D+C–c+E–e+; K–k+; Fy(a–b+); Jk(a+b–)

• Mismatches: C antigen (patient is C+, unit is C–) and Fy(b) antigen (patient is Fy(b–), unit is Fy(b+))
• C antigen mismatch is significant in sickle cell patients
• The Fy(b) mismatch is particularly concerning as the patient has the Fy(a–b–) phenotype (Duffy-null phenotype)

Evidence-Based Rationale

The 2020 American Society of Hematology guidelines strongly recommend prophylactic red cell antigen matching for Rh (C, E or C/c, E/e) and K antigens for patients with sickle cell disease 1. However, when comparing relative immunogenicity:

1. K antigen is considered the most immunogenic of the common antigens, with alloimmunization rates of 5-10% in K-negative recipients receiving K-positive blood 2.

2. C antigen mismatch is particularly problematic in sickle cell patients, with anti-C antibodies developing in approximately 30% of cases with C antigen exposure 2.

3. Duffy (Fy) antigens are also clinically significant, especially in patients with the Duffy-null phenotype Fy(a–b–), which is common in individuals of African descent 1.

4. E antigen, while still important to match, has lower immunogenicity compared to K and C antigens 1, 2.

Clinical Implications

When complete matching is not possible, prioritizing matches based on antigen immunogenicity is crucial:

• K antigen mismatch (Option A) carries the highest risk of alloimmunization
• C antigen mismatch plus Fy(b) mismatch (Option D) presents multiple risks
• E antigen mismatch alone (Option B) presents the lowest risk among the options

Practical Approach

For patients with sickle cell disease requiring chronic transfusion:

1. Always attempt to match for Rh (D, C, c, E, e) and K antigens
2. When complete matching is impossible, prioritize K matching first
3. Then prioritize C/c matching
4. E/e matching should follow
5. Extended matching for Duffy, Kidd, and other systems when possible

In this case, since Option B only has an E antigen mismatch (which is less immunogenic than K or C), it represents the least likely unit to cause alloimmunization in this patient.