University of Texas Southwestern, Texas, United States
Background/Case Studies: Black/African individuals often have lower white blood cell (WBC) and absolute neutrophil counts (ANC) associated with a Duffy null red blood cell (RBC) phenotype commonly caused by homozygosity for a -67T>C polymorphism in GATA-1 on chromosome 1, which is responsible for the majority of Fyb negative phenotypes in this population. This leads to absence of expression of the Fyb antigen on red blood cell (RBC) surfaces, though this antigen remains intact on other physiologic surfaces. While this provides relative resistance to some Plasmodium species, it is unclear the complete impact this has on patients with sickle cell disease (SCD).
Study
Design/Methods: We performed a 1-year retrospective observational study of all patients with SCD (homozygous HbSS or HbS/B0) undergoing chronic RBC exchange at a large, academic pediatric center and two, large adult academic hospitals. We obtained RBC phenotype/genotype, allo-antibody, and complete blood count data. Continuous variables were compared with a Mann-Whitney test and categorical variables were compared using a Fisher’s exact test.
Results/Findings: Our cohort consisted of 99 patients with SCD undergoing chronic RBC exchange. Duffy antigen phenotype was available for 96 patients, and Duffy antigen genotype was available for 19 patients. Amongst genotyped patients, 89% (17/19) had the GATA-1 -67T>C polymorphism, while 82.3% (79/96) of patients were Fy(a-b-) by serologic phenotype. There was no significant difference in WBC count, ANC, alloimmunization, or warm autoantibody rates based on Duffy null phenotype (Table 1). Conclusions: Both groups had elevated WBC levels, high rates of RBC alloimmunization, and high rates of warm autoantibody formation irrespective of Duffy status. This is likely attributed to the chronic inflammatory nature of SCD, though the elevated WBC results differentiate this group from Black/African individuals with Duffy-null associated decreased neutrophil counts. The rate of Duffy-null status, 82.3%, is higher amongst the population with SCD than reported in the general Black/African population, 65-70%, potentially secondary to environmental pressures from varying Plasmodium species impacting both HbS prevalence and the Duffy null RBC phenotype.
Importance of research: Determining risk factors for RBC alloimmunization in sickle cell disease is extremely clinically relevant given the high transfusion burden of these patients. We show that Duffy phenotype does not appear to be associated with these rates in evaluating a large sickle cell disease cohort. We also demonstrate high white counts in both groups, contrasting with Duffy null patients who generally have lower white blood cell counts.
