Rh Factor VS RhD Factor

Bottom Line:

They are the same thing! D is the most common antigen in the Rh blood group system so people keep things simple by just saying “Rh” instead of RhD. Note that RhD can also be denoted as RhO (sometimes using a subscript letter O or number 0). So Rh, RhD, RhO, RhoD, RhO or Rh0 can all refer to the D antigen of the Rh blood group system.

Memory Aids:

When in doubt, it’s the Rh D antigen.


Most of this information comes from the ISBT (International Society of Blood Transfusion), a really great review paper in Blood, and an online book called “Blood Groups and Red Cell Antigens” available on PubMed.

There are apparently 35 blood group systems in humans (although some ISBT documents say 30), the most important being the ABO system followed by the Rh system. Essentially, a blood group system refers to a red blood cell surface antigen (a transmembrane protein) controlled by “either a single gene or a cluster of closely linked homologous genes”. Most of the polymorphisms in these proteins result from SNPs (single nucleotide polymorphisms) which yield single amino acid substitutions.

The Rh blood group system

The Rh blood group system consists of 54 antigens carried on two proteins (RhD encoded by the gene RHD, and RhCE encoded by the gene RHCE). The origin of the name Rh comes from initial studies involving Macacus rhesus (monkeys). The most common Rh antigens are D, C, c, E and e. Because the C/c and E/e antigens are on the same gene, they are inherited together. There is no d antigen and Rhd is sometimes used to denote “RhD negative”. The most commonly occurring patterns in humans are: Dce, dce, DCe, dCe, DcE, dcE, DCE and dCE. These 8 have been given short forms R0, r, R1, r’, R2, r”, Rz, and ry. Notice that “R” is used when D is present and “r” is used when it’s absent. There is also an RhAG (Rh associated glycoprotein) which is related to Rh proteins (RhD and RhCE). RhD and RhCE carry the antigens, but they are only expressed on the red blood cell if RhAG is also present. The absence of Rh factor varies by ethnicity: 17% Caucasian, 7% Hispanic/Black, 2% in Asians.

Rh immunology

The purpose of the Rh antigens is still unknown, but their presence has important clinical implications. The D antigen will produce an immunological response in up to 80% of D negative people when exposed to RhD positive blood. Immunization with D antigens can occur during pregnancy (alloimmunization or sensitization) if the baby is positive, but the mother is negative. Some people even make antibodies against their own Rh antigens (autoimmunization) called autoantibodies. Regardless of the method of immunization (exposure to the Rh antigen), if the immune system makes antibodies against the Rh antigen it can cause hemolytic anemia. In the case of autoantibodies the patient’s antibodies will target their own blood cells and cause them to be destroyed.

Before we go on, a quick immunology review. When exposed to a new antigen the immune system makes antibodies which target the antigen and stick to it. The presence of antibodies stuck to a cell act as signals to other aspects of the immune system to attack and destroy the tagged cell. There are several types of antibody with distinctive shapes and sizes. The first antibodies made are usually IgM. These are large and, in the case of pregnancy, can’t cross the placenta. After some time, the IgM antibodies are no longer produced and IgG antibodies are made. These target the same antigen, but are smaller and can cross the placenta. What happens in the fetus’s body will depend on multiple factors including how much antibody makes it across, what stage of development has been reached, and how specific the antibody is for a particular antigen.

Rh in pregnancy

In an Rh negative mother during a first pregnancy there is usually no risk to the mother or fetus. Rh positive blood from the fetus transfers to the mother some time during pregnancy or delivery and the mother makes IgM antibodies against the Rh antigen. During a subsequent pregnancy, if the second baby is also Rh positive, the mother may have IgG antibodies against the Rh antigen. These will cross the placenta, tag baby’s red blood cells and target them for destruction. This leads to HDN (hemolytic disease of the newborn) which can be mild, moderate, or severe. Mild cases see a tolerable rise in fetal bilirubin levels as fetal RBCs are destroyed. Moderate cases see increases in bilirubin levels which the fetus cannot compensate for and may lead to bilirubin entering the brain and causing brain damage (kernicterus). Severe cases may lead to severe hemolytic anemia and hepatosplenomegaly as the fetal liver and spleen attempt to produce more RBCs. Too many immature RBCs are released into circulation and result in erythroblastosis fetalis.

Maternal-fetal Rh incompatibility ends up being worse than ABO incompatibility because erythrocytes don’t express large amounts of ABO antigens until adult life. Interestingly, sensitization is less likely to occur if there is a maternal-fetal ABO mismatch since any blood cells crossing the placenta to the mother are destroyed by her antibodies against the mismatched ABO antigens.

Rh mismatch treatment

All unsensitised mothers receive anti-RhD antibodies (RhD immune globulin AKA RhoGAM) which will tag and mark for destruction any RhD positive fetal RBCs which have leaked into mom’s circulation. Standard treatment is an injection at 28 weeks gestation when fetal RBCs start to express RhD antigen. Then again at 34 weeks (prior to labour) when risk of fetal-maternal hemorrhage is high. Then a final dose after delivery. Additional doses can be given if there is known antepartum bleeding, pre-eclampsia, or anything which may increase sensitization. The injection is IM. Because these are IgG antibodies, it is the subject of great debate whether or not these antibodies can cross the placenta and lay the proverbial smack down on baby’s RBCs. The best attested consensus opinion I’ve seen is that small amounts of the antibody do in fact cross the placenta, but based on the dosage given to the mother and the amount that crosses the placenta, the effects on baby are very minimal.

Usually only RhD prophylaxis is pursued, not any other Rh antigens or ABO antigens. If mom is known to be sensitized already, it is necessary to assess fetal blood type by testing dad. If dad is homozygous then baby will be D positive 100% of the time (baby will be Rhd/RhD and express at least some Rh factor), if dad is heterozygous fetal blood will have to be tested either from amniotic fluid or the umbilical cord.

If baby shows signs of anemia, a blood transfusion can be done in utero or in the neonatal period. In some jurisdictions, any Rh negative mother is treated with anti-RhD even if she is not known to be sensitized.


The International Society of Blood Transfusion is a great resource.

This paper in the journal Blood is excellent as well.

PubMed has free access to a book called “Blood Groups and Red Cell Antigens” which has a great chapter on hemolytic disease of the newborn.

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