Should phenotype-matched donor units be used to minimize alloimmunization during red blood cell exchange?

From the Guidelines

For red blood cell exchange procedures, using phenotype-matched donor units is strongly recommended to minimize alloimmunization risk, as it significantly reduces the formation of alloantibodies and prevents delayed hemolytic transfusion reactions. The optimal approach involves matching for at least the Rh (C, c, E, e) and Kell (K) antigens, with extended matching for Duffy, Kidd, and MNS systems when possible, as supported by the American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support 1. This is particularly important for patients requiring chronic transfusions, such as those with sickle cell disease. The process begins with comprehensive phenotyping or genotyping of the patient's red blood cells before their first transfusion. Blood banks should then select donor units that match the patient's antigen profile, prioritizing the most immunogenic antigens.

Some key points to consider when implementing phenotype-matched donor units include:

• Determining the extended red cell antigen profile by genotype or serology 1
• Providing further protection from alloimmunization through extended red cell antigen matching (Jka/Jk b, Fya/Fyb, S/s) 1
• Considering the patient's genetic background, such as the GATA mutation in the ACKR1 gene, which encodes Fy antigens, and the hybrid RHDDIIIa-CE (4-7)-D or RHCECeRN alleles, which encode partial C antigen 1
• Prioritizing matching for the most immunogenic antigens (Rh and Kell) in emergency situations when fully phenotype-matched blood isn't available

The biological rationale is that preventing exposure to foreign red cell antigens prevents the immune system from developing antibodies against these antigens, thereby preserving transfusion safety for the patient's lifetime and reducing transfusion-related complications, as demonstrated by the significantly lower incidence rate of red cell alloantibodies per 100 red cell units transfused with Rh- and K-matched red cells compared to ABO/RhD-matched red cells 1.

From the Research

Minimizing Alloimmunization for Red Blood Cell Exchange

To minimize alloimmunization for red blood cell exchange, using phenotype-matched donor units is a crucial strategy. The following points highlight the importance of this approach:

• Determining the Rh/Kell phenotypes in both donors and patients is significant in providing phenotype-matched blood to minimize alloimmunization and transfusion reactions 2.
• Complete RH and Kell matching has been shown to be related to a low alloimmunization risk in patients with sickle cell disease, emphasizing the importance of phenotype matching in reducing the risk of alloimmunization 3.
• Selecting appropriate red blood cell units for exchange is critical to prevent the risk of alloimmunization in patients with sickle cell disease, and understanding alloimmunization risks has led to the development of recommendations for preventing this risk 4.
• Prophylactic red blood cell transfusion with extended antigen matching has been shown to reduce alloimmunization in patients with sickle cell disease, although it does not completely avoid alloimmunization to Rh and low-prevalence antigens 5.
• Phenotyping for Rh/Kell antigens before the first transfusion can significantly reduce the rate of alloimmunization in chronically transfused patients with primary haematological disorders, suggesting that this strategy should be adopted for certain patient groups 6.

Key Considerations

• The frequency of Rh and Kell antigens in donors and patients can vary, highlighting the need for phenotype matching to minimize alloimmunization 2.
• Deviation from complete RH and Kell matching can increase the risk of alloimmunization, even in patients with a high grade of RH-Kell matching 3.
• The risk of alloimmunization increases with transfusion burden, particularly during acute complications, and in patients with a higher number of vaso-occlusive crises 3.
• Extended antigen matching can reduce the rates of alloimmunization but may not completely prevent it, especially for Rh and low-prevalence antigens 5.