Duffy Antibody in Pregnancy: Clinical Significance and Management
Duffy antibodies (anti-Fya and anti-Fyb) are clinically significant alloantibodies that can cause severe fetal anemia and hemolytic disease of the fetus and newborn (HDFN), requiring close surveillance and potential intervention during pregnancy. 1
Risk Assessment and Clinical Significance
Anti-Duffy antibodies are classified among the atypical antibodies "known to cause severe fetal anemia," alongside anti-Kell, anti-Kidd (Jka, Jkb), according to Society for Maternal-Fetal Medicine guidelines. 1 This places them in a high-risk category requiring active management rather than passive observation.
Severity of Disease
Severe HDFN requiring intrauterine transfusions (IUT) or postnatal exchange transfusions occurs in approximately 11% of at-risk pregnancies with anti-Fya when significant antibody titers are present (>64). 2
In a comprehensive review of 68 pregnancies with anti-Fya, three cases (4.4%) resulted in severe fetal anemia, with two requiring intrauterine transfusions. 2
Management guidelines developed for anti-D sensitization are appropriate for pregnancies complicated by anti-Fya alloimmunization, as the potential for significant fetal hemolysis is comparable. 3
Surveillance Protocol
For pregnant women with Duffy antibodies, implement the following monitoring strategy:
Antibody Titer Monitoring
Obtain maternal antibody titers at initial detection and repeat monthly throughout pregnancy. 2
Titers ≥32 indicate increased risk and warrant intensified fetal surveillance. 3
Titers >64 are associated with the highest risk of severe fetal anemia requiring intervention. 2
Fetal Surveillance
Perform serial middle cerebral artery peak systolic velocity (MCA-PSV) Doppler monitoring to detect fetal anemia, following the same protocols used for other alloimmune antibodies. 1
Begin MCA-PSV surveillance when titers reach ≥32 or if there is a history of an affected pregnancy, continuing every 1-2 weeks depending on titer trends and MCA-PSV values. 2, 3
MCA-PSV values >1.5 multiples of the median (MoM) indicate moderate-to-severe fetal anemia and warrant consideration for cordocentesis and possible intrauterine transfusion. 3
Paternal and Fetal Genotyping
When the father is heterozygous for the Duffy antigen and antibody titers are rising or significant (>64), offer fetal genotyping to determine if the fetus is at risk. 2
Fetal genotyping can be performed using cell-free fetal DNA from maternal blood or through amniocentesis with allele-specific polymerase chain reaction (ASPCR), which has 100% concordance with serotyping. 4
If the fetus is Duffy antigen-negative, intensive surveillance can be discontinued, sparing the mother and fetus unnecessary interventions. 2
Common Pitfalls to Avoid
Do not underestimate anti-Duffy antibodies based on outdated literature suggesting they cause only mild disease. While historically considered less severe than anti-D, contemporary evidence demonstrates that anti-Fya can cause severe HDFN requiring IUT in 11% of at-risk pregnancies. 2, 3
Do not rely solely on antibody titers to exclude severe disease. Two cases of severe HDFN due to anti-c occurred with maximum titers of only 8 and 16, though this is less common with anti-Duffy. 5 MCA-PSV Doppler remains the gold standard for detecting fetal anemia.
Do not delay referral to a maternal-fetal medicine specialist when titers reach ≥32 or if there is a history of a previously affected pregnancy, as timely intervention with IUT can prevent hydrops fetalis and perinatal death. 2, 3
Neonatal Considerations
All neonates born to mothers with Duffy antibodies require immediate cord blood testing for hemoglobin, bilirubin, and direct antiglobulin test (DAT). 3
Phototherapy and exchange transfusion may be required for neonatal hyperbilirubinemia, though the risk is lower than with anti-D alloimmunization. 5
No perinatal deaths or hydrops fetalis were reported in recent case series when appropriate surveillance and intervention protocols were followed, emphasizing the importance of proper management. 3