This site is intended for health professionals only

Practice nursing basics: rhesus factor disease

Julie Smith
Specialist Nurse
General Practice Nursing
Chaddlewood Surgery

All blood groups are based on the absence or presence of special proteins attached to the surface of red blood cells. The rhesus factor protein is the next most important one after the A and B proteins. If a person carries the rhesus factor they are Rh-positive. If they do not they are Rh-negative. The gene that causes a person to be Rh-positive is present in about 85% of the UK population.(1)
The importance of blood groups is that someone without a particular blood group protein who is given blood (by transfusion) containing that protein will develop antibodies to it and effectively become allergic to it. For example, people with blood group A do not have the B protein, and giving such a person blood from group B or AB (where both A and B proteins are present) will cause a serious reaction that may lead to death. Someone with blood group O has neither protein, so can receive blood only from another group O donor, but can give blood to any group.
Problems with rhesus factor usually occur only in pregnancy. If a mother is Rh- negative and the baby is Rh-negative there is no problem. However, if the baby is Rh-positive, the mother could become sensitive to the baby's blood. The mother's blood does not usually come into contact with the baby's blood until labour, so the difference is unlikely to cause serious harm in the first pregnancy. However, during a pregnancy and at the time of birth, small amounts of the baby's blood can cross through into the mother's bloodstream. This is very normal and happens in about 75% of pregnancies. As a result, the mother will produce antibodies (blood proteins) to the baby's blood. The process does not harm the baby the mother is currently carrying but could affect future pregnancies.
During that first labour, the mother's body produces antibodies to the rhesus protein. In later pregnancies where the baby is also Rh-positive, the level of these antibodies in the mother's blood rises rapidly. They soon reach a point where they can destroy the red blood cells of the baby. When this happens, babies have haemolytic disease of the newborn (HDN)(1) and the following occurs:

  • The baby's blood is broken down and bilirubin (a bile pigment) is produced. In very high levels this can cause severe brain ­damage, with paralysis, learning difficulties, ­blindness and deafness.
  • The baby is born deeply jaundiced with an enlarged liver and spleen and a low haemoglobin level in the blood (anaemia).
  • In the most severe cases the fetus dies in the uterus, usually after the 28th week.

If an affected baby is born, the diagnosis is obvious. An exchange transfusion, via the umbilical cord, can be done as soon as the baby is born, or even while still in the womb. This corrects the anaemia and gets rid of the bilirubin. Exposure to intense ultraviolet light soon after birth converts the bilirubin in the skin to a form that is harmless to the brain.

Rh-negative women can be prevented from developing antibodies by being given an injection of "anti-D gamma-globulin" within 72 hours of the birth of an Rh-positive baby.
The development of rhesus disease (RhD) generally results from fetomaternal haemorrhages (FMH) in RhD-negative women who carry an RhD-positive fetus. A prevention programme began in the UK in 1969, initially by giving anti-D immunoglobulin (Ig) immediately after delivery. It proved an amazing success, with deaths attributed to RhD sensitisation falling from 46 per 100,000 births before 1969 to 1.6 per 100,000 in 1990.(2)
Nevertheless, RhD continues to occur. In some cases this results from failure to adhere to previously published guidelines on RhD prophylaxis. The most important cause of anti-D antibodies is now immunisation in pregnancy where there has been no overt sensitising event. Late immunisation during a first pregnancy is responsible for 18-27% of cases. Immunisation during a second or subsequent pregnancy probably accounts for a similar proportion of cases, although in this situation it is impossible to distinguish late sensitisation from failure of prophylaxis at the end of the preceding pregnancy.
The current recommendations are taken directly from the updated guidelines drawn up by a joint working group of the British Blood Transfusion Society and the Royal College of Obstetricians and Gynaecologists (RCOG), due for review in September 2002.(3) The key recommendations of these guidelines are as follows:

  • At least 500iu of anti-D Ig should be given to all nonsensitised women at 28 and 34 weeks of ­pregnancy.
  • Following delivery, irrespective of the dose of ­anti-D Ig routinely administered, postnatal prophylaxis must include a screening test to identify women with a large FMH who need additional Ig.
  • Anti-D Ig should be given after potentially ­sensitising events to nonsensitised women before delivery and after abortion. These include antepartum haemorrhages, closed abdominal injury, intrauterine death, invasive prenatal ­diagnosis (amniocentesis, chorion villus sampling, fetal blood sampling and other intrauterine ­procedures.
  • Anti-D Ig is no longer necessary in women with threatened miscarriage with a viable fetus and ­cessation of bleeding before 12 weeks gestation.

The importance of all nonsensitised RhD-negative women receiving anti-D Ig means that if given at the time of the first pregnancy it "mops up" the baby's blood and therefore prevents the mother from producing antibodies to the "foreign" rhesus factor. Once a woman is sensitised to the D-rhesus antigen, anti-D globulin can have no effect. It should be noted that anti-D Ig does not protect against the development of other antibodies that can cause haemolytic disease of the newborn.
It is also paramount that women have all the necessary information to enable informed choice about RhD prophylaxis as anti-D is a blood product and they may have concerns about source, safety and ethical issues.
Professor Robert Shaw, President of the Royal College of Obstetricians and Gynaecologists, has said: "There is now sufficient anti-D available to offer ante-natal prophylaxis to all nonsensitised RhD-negative women. This should make a rare cause of neonatal deaths ever rarer."


  1. British Committee for Standards in Haematology. Guidelines for blood grouping and red cell antibody testing during pregnancy. Transfus Med 1996;6:71-4.
  2. Mollinson PL, Engelfriet CP, Contreras M. Haemolytic disease of the newborn. In: Blood transfusion in clinical medicine. 10th edn. Oxford: Blackwell Science; 1997. p. 414.
  3. Joint Working Group of the British Blood Transfusion Society and RCOG. Recommendations for the use of anti- D immunoglobulin for Rh prophylaxis. Transfus Med 1999;9:93-7.

Health Evidence Bulletins: Wales
Duthrie Library, UWCM, Cardiff
T:029 20 745142
F:029 20 743574
NHS Direct
Online Health Encyclopedia