Implications of ACKR1 genotype and Duffy status

Implications of ACKR1 genotype and Duffy status

	ACKR1 genotype/Duffy phenotype
	Duffy-null^¶	Non-Duffy-null
Hemolytic transfusion reactions (HTRs)^Δ	Alloimmunization and HTRs can occur if non-Duffy-null blood is transfused (mostly applies to Fy^a positive).	Alloimmunization and HTRs can occur if Fy^a positive RBCs are transfused to a recipient who is Fy^a negative. Alloimmunization and HTRs can occur if Fy^b positive RBCs are transfused to a recipient who is Fy^b negative.
Hemolytic disease of the fetus and newborn (HDFN)^◊	HDFN can occur if the mother is Fy^a negative and the father is Fy^a positive.	HDFN can occur if father expresses Fy^a and mother is Fy^a negative.
ANC normal range	Lower ANC range than non-Duffy-null.	Higher ANC range than Duffy-null.
Risk of infections	No increased risk of bacterial infections. Protection from P. vivax and P. knowlesi malaria. Possible altered risk or disease course for HIV compared with non-Duffy-null individuals.	No increased risk of bacterial infections. No protection from P. vivax and P. knowlesi malaria. Possible altered risk or disease course for HIV compared with Duffy-null individuals.
Drug dosing	Drug dosing should not be altered based on baseline ANC (consider Duffy-null specific reference ranges).
Relatives	May benefit from knowing their status for reasons mentioned above.

Information about ACKR1 genotype or Duffy phenotype may help individuals understand their risk of transfusion reactions and HDFN, but serologic testing is the gold standard. Information about normal neutrophil ranges can help individuals avoid unnecessary evaluations and can avoid inadvertent withholding or under-dosing medications that affect the neutrophil count, a practice that affects predominantly people with African ancestry. For identifying Duffy-null status, serologic testing for Fy^a and Fy^b or genetic testing of ACKR1 can be used. Genetic testing is especially helpful if serologic typing results are inconsistent with the antibody screen or if the patient has been recently transfused.

ACKR1: atypical chemokine receptor 1; ANC: absolute neutrophil count; Fy: Duffy antigen; HDFN: hemolytic disease of the fetus and newborn; HIV: human immunodeficiency virus; HTR: hemolytic transfusion reaction; P. knowlesi: Plasmodium knowlesi; P. vivax: Plasmodium vivax; RBC: red blood cell.

¶ Other designations for Duffy-null include:

c.-67 C/C
Homozygous c.-67T>C
Homozygous rs2814778-C
FY*B^ES/*B^ES
Fy(a–b–)

Δ Pretransfusion testing is routinely used to avoid antigens implicated in hemolytic transfusion reactions.

◊ Maternal antibody screen is routinely performed during pregnancy to identify risk for HDFN and the need for additional testing and monitoring. Only anti-Fy^a has been associated with HDFN.

Graphic 140075 Version 2.0

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Implications of ACKR1 genotype and Duffy status