Management of Pregnancy in Mothers with Anti-Kell Antibodies

Determine Whether the Fetus Is at Risk

Current guidance—including ACOG Practice Bulletin No. 192: Management of Alloimmunization During Pregnancy (2018) and the 2024 review by Moise & Abels—begins with evaluating the biological father's Kell status to determine whether the fetus is at risk of inheriting the K antigen.

To determine the father's Kell phenotype order Red Blood Cell Antigen Typing, Kell antigen (006068). For paternal Kell genotype (K/k), order Kell K/k (KEL) Antigen Genotyping 3002001.

• If father is Kell-negative (paternity assured): the fetus is not at risk and no Kell-specific monitoring is required.
• If father is Kell-positive: consider paternal genotype:
  • Homozygous K/K: fetus is an obligate Kell-positive carrier → manage as Kell-positive fetus without further antigen testing.
  • Heterozygous K/k: ~50% risk that the fetus is Kell-positive → fetal Kell antigen testing is indicated.
• If paternal status is unknown or testing not available: manage as if the fetus is potentially Kell-positive and consider fetal genotyping.

Fetal antigen testing options (when fetal status is not known from paternal genotype):

• cfDNA fetal Kell genotyping (noninvasive)
• Amniocentesis with PCR genotyping when cfDNA is unavailable, inconclusive, or not validated in a given setting

*Studies of cell-free fetal DNA Kell genotyping report very high sensitivity and specificity (≈>99%), which yields an excellent negative predictive value when the assay reports a Kell-negative fetus.

Maternal Antibody Titers Should Not Guide Fetal Surveillance

• A critical titer is defined as the anti–red cell titer associated with a significant risk for fetal anemia. Critical titers used for anti-D (e.g., 1:16) should not be applied to Kell.  For anti-K1 (Kell and anti-c) a critical value of 4 or greater has been suggested.
• Unlike RhD alloimmunization, anti-Kell titers do not reliably predict fetal anemia. Anti-Kell antibodies can suppress fetal erythropoiesis, so fetuses may become profoundly anemic despite low or stable maternal titers. ACOG Practice Bulletin No. 192 and subsequent reviews emphasize that Kell titers are not dependable indicators of disease severity.
• Although maternal titers are useful for documentation they should not guide fetal surveillance or delay MCA Doppler evaluation in at-risk pregnancies.

Surveillance for At-Risk or Kell-Positive Fetuses: MCA Doppler

If the fetus is Kell-positive (by genotype or obligate status from a homozygous K/K father) or fetal status is unknown, noninvasive monitoring for fetal anemia should be performed using middle cerebral artery peak systolic velocity (MCA-PSV).

• Start MCA-PSV at 16–18 weeks in at-risk pregnancies.
• Repeat every 1–2 weeks, depending on prior values and clinical context.
• MCA-PSV ≥ 1.5 MoM suggests moderate or severe fetal anemia.

Calculator: Expected Peak Velocity of Systolic Blood Flow through the MCA

Management Flowchart for Anti-Kell Alloimmunization

Invasive Diagnosis and Therapy (When Indicated)

If MCA-PSV reaches or exceeds 1.5 MoM, evaluation at a fetal therapy center is recommended. Confirmatory testing via percutaneous umbilical blood sampling (PUBS) may be required, followed by intrauterine transfusion when significant fetal anemia is confirmed.