Technical Specialist II Johns Hopkins Hospital Baltimore, Maryland, United States
Background/Case Studies: There is renewed interest in identification of Duffy null (Fy(a-b-)) associated neutrophil count (DANC). Though DANC lacks apparent clinical consequence, failure to diagnose may promote unnecessary clinical evaluation or exclusion from therapies. Identifying DANC in patients with sickle cell disease (SCD) informs hydroxyurea (HU) dosing. The Fy(a-b-) phenotype is common in Blacks (68%), and rare in Whites (< 1%); however, testing based solely on reported race/ethnicity may miss a DANC diagnosis.
Study
Design/Methods: Serologic phenotyping of Fya and Fyb was performed using commercial antisera by tube technique per the manufacturer’s instructions. FY genotype analysis was performed by a commercial multiplex PCR test, which includes analysis of the –67T >C single nucleotide variation (SNV) to predict Fyb antigen status. This single center retrospective study investigated the clinical, demographic, and laboratory data of patients referred for Fya/Fyb antigen testing for suspected DANC.
Results/Findings: FY antigen testing was requested for 23 patients (median age 11yrs, interquartile range [4-16yrs]) of whom 74% (n=17/23) were male and 22% (n=5/23) had a history of SCD on HU. The self-reported race/ethnicities were Black (74%, n=17/23), Asian (17%, n=4/23), and White (9%, n=2/23). Of these, 91% (n=21/23) were serologically phenotyped, one patient was genotyped and one patient had both. Of the 23 patients tested, 83% (n=19/23) were Fy(a-b-), whereas the remainder (17%, n=4/23) were FY antigen positive. One Fy(a-b-) patient with White race was confirmed to be homozygous for the –67T >C SNV in the FY*B promoter region disrupting GATA1 binding. The peripheral smear was normal in 12 Fy(a-b-) patients. No patients had a bone marrow evaluation. Five Fy(a-b-) patients had a history of infection (e.g., otitis media); however, only one patient with adenovirus infection was hospitalized. As compared to FY antigen positive, Fy(a-b-) patients had significantly lower median white blood cell counts 3.91K/ cu mm versus 6.91K/ cu mm (p=0.035), Mann Whitney U), but median absolute neutrophil counts (ANC) were not different 1,080/uL versus 1,193/uL (p=0.356, Mann Whitney U). Among the 5 patients with SCD, all were tested for DANC —and Fy(a-b-)— after multiple interruptions in their HU treatment. Conclusions: In unexplained neutropenia, DANC should be investigated. FY antigen phenotyping is rapid and can be performed by a transfusion service to aid in the evaluation of DANC. Referrals should not exclude patients based on reported race/ethnicity, as our study did include a White patient who was Fy(a-b-). DANC diagnosis lowers the threshold for a tolerable ANC in SCD patients on HU to allow for dose escalation and prevent interruption of therapy.
