Transfusion medicine

Red blood cell antigens

Rh group

Editorial Board Member: Kyle Annen, D.O.
Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.
Brian D. Adkins, M.D.
Garrett S. Booth, M.D., M.S.

Last author update: 1 June 2021
Last staff update: 2 June 2021

Copyright: 2020-2023,, Inc.

PubMed Search: transfusion Rh group antigens "free full text" [SB] pathology

Brian D. Adkins, M.D.
Garrett S. Booth, M.D., M.S.
Page views in 2022: 266
Page views in 2023 to date: 157
Cite this page: Adkins BD, Booth GS. Rh group. website. Accessed June 9th, 2023.
Definition / general
  • Most antigenic blood group outside of ABO
  • Antibodies are clinically significant
Essential features
  • Rh (Rhesus) antigens are widely expressed in the donor population
  • Antibodies can cause hemolysis and hemolytic disease of the fetus and newborn (HDFN)
  • Type: peptide
    • RhD is an antigen formed by RHD on chromosome 1
      • D antigen has high frequency among all racial groups and products are designated as positive or negative based on its presence
      • D variants include individuals who express less D antigen (weak D) and those who express structurally different D antigen (partial D)
      • Partial D individuals may form antibodies against a normal D antigen
      • Reference: AABB: Technical Manual, 19th Edition, 2017
    • RHCcEe are antigens generally coinherited with RhD on chromosome 1 encoded by the RHCE gene
    • The D antigen is most immunogenic, though other Rh antigens are very immunogenic and patients who alloimmunize at higher rates, such as individuals with sickle cell disease, are often matched for RhCc and RhEe antigens
    • RHAG is a glycoprotein that helps localize Rh antigens to the red cell membrane; absence of this protein leads to RhNull disease
      • RhNull disease is characterized by stomatocytosis, enhanced osmotic fragility and mild chronic hemolysis
    • Rh antigens form structural epitopes, which may be separately antigenic
      • G antigen is formed by four shared amino acids between RhD and RhC
      • f antigen is a compound antigen found on red cells with Rh antigens ce
    • Dce / CE in trans configuration leads to decreased RhD expression due to the Ceppellini effect; the decrease in D expression is most pronounced in the trans configuration but is present to a lesser extent in cis individuals as well (AABB: Technical Manual, 19th Edition, 2017)

    Race / Ethnicity
    White non-Hispanic 82.7% 17.3% 68% 80% 29%
    Hispanic 92.7%   7.3%
    Black non-Hispanic 92.9%   7.1% 27% 96% 22%
    Asian 98.3%   1.7%
    Native American 90.3%   9.7%
    All donors 85.4% 14.6% 98%
    Adapted from Transfusion 2004;44:703, AABB: Technical Manual, 19th Edition, 2017
  • Majority IgG, fewer IgM (AABB: Technical Manual, 19th Edition, 2017)
  • Can cause hemolytic reactions and hemolytic disease of the fetus and newborn
  • Occur with exposure to products containing Rh incompatible blood or pregnancy
  • Show dosage and improve with enzyme treatment
Fisher-Race Haplotype
Modified Wiener Haplotype
DCe R1
DcE R2
Dce R0
ce r
Ce r'
cE r"
CE ry
  • RhD sensitization occurs during the first pregnancy due to maternal exposure to fetal hemorrhage during gestation or delivery; this leads to an anti-D IgG antibody which can cross the placenta in subsequent pregnancies, leading to hydrops fetalis if not identified by obstetrics teams (AABB: Technical Manual, 19th Edition, 2017)
  • Risk of sensitization in an RhD negative mother with an RhD positive fetus is 16%, though this is reduced to < 0.1% with appropriate Rh immunoglobulin administration (AABB: Technical Manual, 19th Edition, 2017)
    • 1 vial of RHIg binds 30 mL whole blood or 15 mL RBC
  • Alloimmunization in healthy individuals can be high; however, rates in hospitalized patients and trauma patients tend to be lower
  • RhD remains the most immunogenic antigen due to its density on the red blood cell surface and amino acid differences from RhCc / Ee
  • Exposure to Rh antigens secondary to pregnancy or transfusion
  • RhD positivity is determined
  • O negative blood is the preferred universal donor blood type in emergency situations; many hospitals will provide RhD positive units in massive transfusion protocols, as RhD alloimmunization is of lower risk in this population; however, women of childbearing age (<50 years) should always receive RhD negative products
Case reports
  • RhIg dosage may be administered in pregnant patients and in patients after exposure to RhD positive products
  • RhD negative mothers with RhD positive partners receive a vial at 28 weeks gestation and after delivery
  • In the situation of maternal fetal hemorrhage or other RhD exposure, a Kleihauer-Betke test may be performed in order to calculate RhIg dosing
  • 1 vial contains 300 μg and theoretically should bind 30 mL of RhD positive or fetal blood
  • Volume in ml of fetal blood = percentage of fetal cells x 50
  • Volume of fetal blood/30 ml = number of vials of 300 mcg RhIg
  • Number of vials = percentage of fetal cells x 50 / 30
  • Round based on the tenth position after the decimal
    • < 0.5, round down and add one vial
    • ≥ 0.5, round up and add one vial
  • Labs may also determine RhIg dosing using flow cytometry
  • Reference: Krywko: Kleihauer Betke Test [Accessed 12 October 2020]
Board review style question #1
A 27 year old mother of 2 presents at the OB/GYN. The mother is O- and has never received prenatal care. No heart rate is detected on Doppler and an ultrasound is performed. A hydropic fetus is identified. If no significant fetal maternal hemorrhage occurred in her prior pregnancies, when should this mother have received RhIg to prevent this outcome?

  1. At 8 weeks and 35 weeks
  2. At 28 weeks and after delivery
  3. At 28 weeks and 35 weeks
  4. Only after delivery
  5. Only at 28 weeks
Board review style answer #1
B. At 28 weeks and after delivery. Mothers are dosed at 28 weeks and at delivery to prevent RhD alloimmunization. The rate of RhIg failure is < 0.01%.

Comment Here

Reference: Rh group
Board review style question #2
A 36 year old man is seen for a viral illness by his primary care physician. A complete blood count is performed and the patient is found to have mild anemia. The physician is concerned and orders a peripheral smear review at a follow up appointment, which is read as mild anemia with anisopoikilocytosis including frequent stomatocytes. What Rh abnormality may this patient have?

  1. DCe / Ce in trans configuration
  2. Partial D
  3. Partial e
  4. Weak D
  5. RhNull phenotype
Board review style answer #2
E. RhNull phenotype. This lack of all Rh antigens leads to structural abnormalities (stomatocytes) and chronic mild anemia, which is generally not clinically significant.

Comment Here

Reference: Rh group
Back to top
Image 01 Image 02