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Pregnancy-Related RBC Alloimmunization in Sickle Cell Trait Patients; A Single-Center Experience


 
 
 Sickle Cell Disease (SCD) is an autosomal recessive disorder, which results from a point mutation in the Î²-globin gene. The production of mutant Hb S (V6E) leads to hemolytic anemia and numerous clinical complications. Patients homozygous for HbS gene (SS) typically rely on life-long transfusion therapy. Alloimmunization to foreign RBC antigens in multiply transfused patients is significantly more frequent in SS patients (observed in 7–47%) compared to patients with HbA (AA), and can pose a significant hurdle in finding compatible RBCs. However, the mechanism for enhanced alloimmunization in SS patients has not yet been elucidated. Patients heterozygous for HbS (SA) have a no distinct clinical phenotype and do not typically require transfusions. We investigated the rate of RBC antigen alloimmunization and specificity in SA patients.
 
 
 
 The aim of this study was to determine and compare the rate and specificities of RBC antigen pregnancy-related alloimmunization in SA and AA patients.
 
 
 
 In our retrospective study, we identified females who delivered a newborn between January 2014 to October 2019, for whom prenatal hemoglobin electrophoresis testing, and prenatal and perinatal antibody screening and identification was performed. R (V.3.6.2) statistical computing program was used for analysis.
 
 
 
 A total of 41735 subjects were identified: 40058 (AA) and 1677 (SA). African Americans were more prevalent in the SA compared to the AA group (55.8% vs 29.4%, P<0.01)and were more likely to have received ≥ 1 transfusion during pregnancy (4.5% vs 3.3%, P<0.01). A total number of 267 alloantibodies were detected in 246 patients (0.6% of the studied population) during pregnancy, 228 patients (0.6%) in the AA group and 18 patients (1.1%) in the SA group.229/246 (93%) of patients with antibodies did not receive transfusion during pregnancy, and thus antibodies were considered to represent pregnancy-related alloimmunization. In non-transfused subjects the SA group were more likely to have developed alloantibodies in pregnancy compared to the AA group [OR= 1.94, P=0.015]. The median age of patients with antibodies in the SA was older [33.5 vs 27 (p=0.008)] as compared to those in the AA group [29 vs 27 (p=0.002)].
 The most common antibody identified was anti-E (SA 42% vs AA 28%), anti-Lea (SA 21% vs AA 13%) and anti-C (SA 5% vs AA 12%). Subjects with pre-existing alloantibodies had a 5.4x increased risk of forming a new allo-antibody. However only 0.1% of subjects had a history of prior allo-antibodies, with no significant difference identified between AA and SA.
 
 
 
 SA patients were found to have an increased rate of pregnancy-related alloimmunization (OR 1.75, P=0.02) after adjusting for the effects of increasing age, RH type, ethnicity, number of previously existing antibodies and number of transfusions in pregnancy.
