Extended Matching of Red Cell Antigens for Patients with Sickle Cell Anemia Decreases the Rate of Alloimmunization.
Authors: Ambruso Daniel R. , LaSalle-Williams Michele , Le Tuan , Cole Laura , Hassell Kathy , Billington Christian , Nuss Rachelle 
Published: October 2019

Abstract
Introduction: Transfusions of packed red blood cells (PRBCs) remain an important treatment for the severe complications of sickle cell anemia. A major complication of transfusions, however, is the formation of alloantibodies to minor red cell antigens. Since 1978 we have provided extended matching for sickle cell patients requiring chronic or intermittent transfusions. We present here a review of our experience with extended matching for decreasing the rate of alloimmunization.
Methods: Records of patients with sickle hemoglobinopathies enrolled in the Colorado Sickle Cell Treatment and Research Center between December 31, 1993 and January 1, 2006 were reviewed under a protocol approved by the COMIRB at UCDHSC. At enrollment, serologic testing was completed on patients for the following blood group antigens: ABO; Rhesus (C,c,D,E,e); Kell (K,k); Duffy (Fya,Fyb); Kidd (Jka,Jkb); Lewis (Lea,Leb); and MNS (M,N,S,s). Donors were typed for the same antigens. For all transfusions, a perfect match was sought. Perfect matches for Rhesus, Kell, Duffy (Fya) and Kidd were an absolute requirement. Mismatches were allowed for Fyb and MNS when an identical match could not be found because of lower risk of sensitization and for Le because of infrequent hemolytic transfusion reactions. Antibody screens were completed as part of crossmatch technique at the time of each transfusion by standard methods. When an antibody screen was positive, standard antiglobulin and enzyme techniques and cell panels were used to identify the antibody. For the purposes of this study, the extent of matching and numbers and types of antibodies was determined.
Results: The study population included 104 patients who received transfusions exclusively on the matching protocol; 57 were males and 47 were females. The age of first transfusion ranged from the first year of life to 19.7 years (mean 7.5 years). Hemoglobinopathies included 90 Hgb SS, 11 Hgb SC, and 3 HbS β-thalassemia. During the study, 6,978 transfusions of PRBCs were administered; mean per patient, 68; range 1–519. Of the total number of transfusions, 525 were exactly matched for all antigens. When mismatches for Le, Fyb and MNS were discounted, 6,217 were exactly matched. Of 104 patients, seven (6.7%) developed one alloantibody each: 1 anti-Lea, 1 anti-Kpa, 2 anti-M and 3 anti-D mosaic. Because the three patients who developed anti-D were mosaics and typed as Rh(D) positive, they would have developed antibodies with any approach to providing PRBCs. Excluding these three, the rate of antibody production was 0.06 antibodies per 100 units transfused. This represents more than a 50-fold decrease in development of alloantibodies compared to typing for ABO and Rh(D) alone (historical controls, 33% of patients alloimmunized, 3.5 antibodies/100 units transfused). Minimal difficulties were encountered in the patients who had developed alloantibodies; matching appropriate units to the antibodies and antigens in their phenotype were not difficult.
Conclusion: Extended matching of red cell antigens dramatically reduces the rate of alloimmunization in patients with sickle cell anemia. Whenever possible, extended matching beyond Rhesus and Kell should be considered to avoid antibodies to minor red cell antigens and their complications.