Blood groups rhesus negative pregnancy

Rhesus blood group system

The term Rhesus (Rh) blood group system refers to the 5 main Rhesus antigen s (C, c, D, E and e) as well as the many other less frequent Rhesus antigens. The terms Rhesus factor and Rh factor are equivalent and refer to the Rh D antigen only.

Individuals either have, or do not have, the Rhesus factor (or Rh D antigen) on the surface of their red blood cell s. This is usually indicated by ‘RhD positive’ (does have the RhD antigen) or ‘RhD negative’ (does not have the antigen) suffix to the ABO blood type . Unlike the ABO antigens, the only ways antibodies are developed against the Rh factor are through placental sensitization or translation. That is, if a person who is RhD-negative has never been exposed to the RhD antigen, they do not possess the RhD antibody. [Talaro, K.P. “Foundations in Microbiology. 5th Edition”. Boston: McGraw Hill, 2005. 510-511.] The ‘RhD-‘ suffix is often shortened to ‘D pos’/’D neg’, ‘RhD pos’/RhD neg’, or +/-. The latter is generally not preferred in research or medical situations, because it can be altered or obscured accidentally.

There may be prenatal danger to the fetus when a pregnant woman is RhD-negative and the biological father is RhD-positive. But, as discussed below, the situation is considerably more complex than that.

The Rhesus system is named after the Rhesus Macaque , following experiments by Karl Landsteiner and Alexander S. Wiener , which showed that rabbits, when immunized with rhesus monkey red cells, produce an antibody that also agglutinates the red blood cell s of many humans. Landsteiner and Wiener discovered this factor in 1937 (publishing in 1940). [Landsteiner K, Wiener AS. “An agglutinable factor in human blood recognized by immune sera for rhesus blood.” Proc Soc Exp Biol Med 1940;43:223-224.] The significance of the Rh factor was soon realized. Dr. Phillip Levine working at the Newark Beth Israel Hospital made a connection between the Rh factor and the incidence of erythroblastosis fetalis , and Wiener realized adverse reactions from transfusions were also resulting from the Rh factor. Wiener then pioneered the exchange transfusion to combat erythroblastosis fetalis in newborn infants. This transfusion technique saved the lives of many thousands of infants before intrauterine transfusion was invented which enabled much more severely affected fetuses to be successfully treated. Drs. Neva Abelson and L.K. Diamond co-discovered a simple test for the Rh factor which was widely applied. [ [ Wsutoday] Test for Rh factor]

The Rhesus system has two sets of nomenclatures, one developed by Fisher and Race and one by Wiener. Both systems reflected alternative theories of inheritance. The Fisher-Race system, which is more commonly in use today, uses the CDE nomenclature. This system was based on the theory that there are three closely linked genes on each chromosome. The genes were designated as D and its hypothetical allele d; C and its allele c, E and its allele e. Each gene was supposed to control the product of the corresponding antigen (e.g., D gene produces D antigen, and so on). However, the d gene was hypothetical, not actual.

The Wiener system used the Rh-Hr nomenclature. This system was based on the theory that there was one gene at a single locus on each chromosome of the pair which controls production of multiple antigens. In this theory a gene R is supposed to give rise to the “blood factors” Rho, rh’, and hr” and the gene r to produce hr’ and hr”.

Notations of the two theories are used interchangeably in blood banking (e.g., Rho(D)). Wiener’s notation is more complex and cumbersome for routine use. Because it is simpler to explain, the Fisher-Race theory is more widely used.

DNA testing has shown that both theories are partially correct.Fact|date=June 2008 There are in fact two linked genes, one with multiple specificities and one with a single specificity. Thus, Wiener’s postulate that a gene could have multiple specificities (something many did not give credence to originally) has been proven correct. On the other hand, Wiener’s theory that there is one gene has proven incorrect, as has the Fischer-Race theory that there are three genes.

The Rhesus system antigens

The proteins which carry the Rhesus antigens are transmembrane proteins, whose structure suggest that they are ion channel s [] . The main antigens are C, D, E, c and e, which are encoded by two adjacent gene loci, the RHD gene which encodes the D antigen [] ) and the RHCE gene which encodes both the C and E antigens [] . There is no d antigen. Lowercase “d” indicates the absence of the D antigen (the gene is usually deleted or otherwise nonfunctional).

Hemolytic disease of the newborn

This condition occurs when there is an incompatibility between the blood types of the mother and the baby. These terms do not indicate which specific antigen-antibody incompatibility is implicated. The disorder in the fetus due to rhesus-D incompatibility is known as erythroblastosis fetalis.

* hemolytic comes from two words: hemo (blood) and lysis (destruction) or breaking down of red blood cells

* erythroblastosis refers to the making of immature red blood cells

* fetalis refers to the fetus

When the condition is caused by the RhD antigen-antibody incompatibility, it is called RhD Hemolytic disease of the newborn (often called Rhesus disease or Rh disease for brevity). Here, sensitization to Rh D antigens (usually by feto-maternal transfusion during pregnancy) may lead to the production of maternal IgG anti-RhD antibodies which can pass through the placenta . This is of particular importance to RhD negative females of or below childbearing age, because any subsequent pregnancy may be affected by the Rhesus D hemolytic disease of the newborn if the baby is Rh D positive. The vast majority of Rh disease is preventable in modern antenatal care by injections of IgG anti-D antibodies ( Rho(D) Immune Globulin ). The incidence of Rhesus disease is mathematically related to the frequency of RhD negative individuals in a population, so Rhesus disease is rare in East Asian s, South American s, and Africans , but more common in Caucasians.

*Symptoms and signs in the Fetus:

** Enlarged liver, spleen, or heart and fluid buildup in the fetus’ abdomen seen via ultrasound.

*Symptoms and signs in the Newborn:

** Anemia which creates the newborn’s pallor (pale appearance).

** Jaundice or yellow discoloration of the newborn’s skin, sclera or mucous membrane. This may be evident right after birth or after 24 – 48 hours after birth. This is caused by bilirubin (one of the end products of red blood cell destruction).

** Enlargement of the newborn’s liver and spleen.

** The newborn may have severe edema of the entire body.

** Dyspnea or difficulty breathing.

The frequency of Rh factor blood types and the RhD neg allele gene differs in various populations.

The Rh(D) antigen is inherited as one gene (RHD) (on the short arm of the first chromosome, 1p36.13-p34.3) with two alleles, of which Rh+ is dominant and Rh− recessive. The gene codes for the RhD polypeptide on the red cell membrane. Rh− individuals lack a functional RHD gene (“dd” genotype) do not produce the D antigen, and may be sensitized to Rh+ blood.

Two very similar epitope s are encoded on the same protein on the adjacent related RHCE gene, “Cc” and “Ee”. It is believed that the RHD gene arose by duplication of the RHCE gene during primate evolution. Mice have just one RH gene [] .

The Rhesus system is much more complex than the ABO blood type system because there are more than 30 combinations possible. [ [ Genetics of Rhesus Factor] ]

In testing, D positive blood is easily identified. Units which are negative for D are often retested to rule out a weaker reaction. This was previously referred to as D u , which has fallen out of favor. [Mark E. Brecher, MD, Chair and Editor. Technical Manual. 2005. 15th Edition. AABB, Bethesda, MD, United States. page 322] In some cases, this phenotype occurs because of an altered surface protein that is more common in people of African descent. The testing is difficult, since using different anti-D reagents, especially the older polyclonal reagents, may give different results.

The practical implication of this is that people with this sub-phenotype will have a product labeled as “D positive” when donating blood. When receiving blood, they are sometimes typed as a “D negative”, though this is the subject of some debate. Most “Weak D” patients can receive “D positive” blood without complications. [Mark E. Brecher, MD, Chair and Editor. Technical Manual. 2005. 15th Edition. AABB, Bethesda, MD, United States. page 323] This is important, since most blood banks have a limited supply of “D negative” blood. Patients who test as “D negative” and whose “D positive” status is detectable with an IAT are commonly given “D negative” blood, but this is also debated. [Mark E. Brecher, MD, Chair and Editor. Technical Manual. 2005. 15th Edition. AABB, Bethesda, MD, United States. page 323-4]

This may lead to the unusual situation where a person is “D positive” as a donor but receives “D negative” blood. Since autologous donations are labeled with the blood type and matching the blood type is part of routine pre-transfusion clerical checks, this can easily lead to confusion.

43 other Rh group antigens have been described, but they are either much less frequently encountered or are rarely clinically significant. Each is given a number, though the highest assigned number (Rh56 or CENR) is not an accurate reflection of the antigens encountered since many (e.g. Rh38) have been combined, reassigned to other groups, or otherwise removed. [Mark E. Brecher, MD, Chair and Editor. Technical Manual. 2005. 15th Edition. AABB, Bethesda, MD, United States. page 324]

*Mollison PL, Engelfriet CP and Contreras M. Blood Transfusion in Clinical Medicine. 1997. 10th edition. Blackwell Science, Oxford, UK.

Rhesus negative blood and pregnancy

You may be told you have rhesus negative blood during pregnancy screening. Read about the impact your Rh factor can have and what this means for you and your baby.

At your first antenatal appointment you are likely to be offered several blood tests. One of the tests is to find out your blood group. Your blood may be in one of four groups: A, B, AB or O.

The blood will also be either ‘rhesus positive’ or ‘rhesus negative’. People whose blood is rhesus positive have a substance known as D antigen on the surface of their red blood cells. Rhesus negative people do not. About 15% of women are rhesus negative. This isn’t usually a concern for a first pregnancy, but it may mean some extra care is needed to avoid problems if you get pregnant again.

Does my baby have the same type of blood as I do?

A woman with rhesus negative blood in pregnancy can be pregnant with a rhesus positive baby if the baby’s father is rhesus positive. If any of the baby’s blood enters the woman’s bloodstream, the woman’s immune system can develop antibodies (infection-fighting proteins) against the rhesus antigens. This is known as sensitisation. A transfer of blood can occur during birth, or if the woman has a bleed or an injury.

Risks of rhesus negative blood in second pregnancy

Production of the antibodies is not a problem in a first pregnancy, but when a woman with a rhesus negative blood type is pregnant next time with a rhesus positive baby, her antibodies can attack that baby’s red blood cells. This can result in a serious condition called haemolytic disease of the newborn, which leads to anaemia and jaundice in the baby.

Anti-D injection

If the woman is given an injection of a solution called ‘Anti-D’, it will ‘mop up’ any rhesus positive antigens, preventing production of antibodies against the baby. Anti-D injections reduce the risk of a rhesus negative woman becoming sensitised.

NICE recommends routine antenatal administration of Anti-D to all rhesus negative women in case sensitisation occurs. This can be given as a one-off dose at 28-30 weeks or as two doses at 28 and 34 weeks. It is quite safe for both the mother and the baby.

Further information

NCT’s helpline offers practical and emotional support in all areas of pregnancy, birth and early parenthood: 0300 330 0700. We also offer antenatal courses which are a great way to find out more about birth, labour and life with a new baby.

NICE provides guidance for women and their partners on Routine antenatal anti-D prophylaxis for women who are rhesus D negative.

What Is Your Blood Group? Doctors Find It Can Affect Your Pregnancy & Your Baby


Recent research has established some strong relationships between your blood group, pregnancy and baby’s health. If you do not know your blood group, it is recommended to get a blood test and find out your blood type. Once you’re ready, understand what a certain blood type can mean for you and your unborn baby.

1. Your Blood Group Can Affect Your Fertility

Every woman has a certain “ovarian reserve” – which is basically the capacity of the ovary to provide eggs. Your fertility levels directly depend on this, and this in turn depends on your body’s production of FSH (follicle-stimulating hormone). A follicle is a small cavity inside which the egg grows. It has been found that a woman’s blood group influences the production of FSH. If FSH levels are higher than 10, your fertility goes down.

  • If your Blood Group is O: Women with O blood group are likelier to have FSH higher than 10. There is thus a risk that they might have a lower egg count and poorer egg quality. This makes such women more vulnerable to suffering from fertility problems or difficulty in conceiving.


2. Your Blood Group Can Determine Success/Failure of IVF

Some experts believe that your blood group affects your chances of success or failure in an IVF (in vitro fertilization) procedure. Many couples who face problems in conceiving now undergo IVF, which involves fertilising the egg with the sperm in the lab and implanting it in the woman’s uterus. The woman’s immune system needs to recognise this object and not reject/destroy it as a ‘foreign’ body.

  • If your Blood Group is O: you are less likely to have successful IVF treatment. Many women with O blood group experience a strong, negative immune response to the ‘foreign material’, and their bodies reject it, leading to failure to conceive.

3. Do You & Your Baby Have ‘Compatible’ Blood Groups?

The blood group of your baby gets decided on the basis of your and your partner’s blood groups. If you and your baby don’t have compatible blood groups, it will affect the antibodies produced in your body when the two types of blood mix. This can create problems for your baby for as long as he is in your womb.

  • Mother is Rh Negative & Father is Rh Positive: In this case, if your baby has Rh negative blood group too, there will be no complications. However, if your baby’s blood group is Rh Positive, this is called Rh incompatibility. In this case, the mother’s body might treat the Rh proteins in the baby’s blood as ‘foreign’ and attack them. When the two blood groups mix in any way, it leads to a condition called Rhesus disease. This is a disease that destroys the baby’s blood cells, and could tragically lead to jaundice, brain damage, heart failure, or even death.

  • Mother’s Blood Group is O & Father’s Blood Group is A or AB: The baby might have blood group A, B or AB. This is is called ABO incompatibility. In this case, sometimes, the mother’s body attacks the baby’s red blood cells by producing antibodies against it.
  • 4. Your Blood Group Can Determine Your Baby’s Risk of Anaemia and Jaundice

    When you are pregnant for the first time, your baby is usually protected until birth because your blood cannot cross the placenta. However, if you are exposed to any of these conditions, your and your baby’s blood may mix sooner than delivery:

    • miscarriage
    • injury that causes bleeding
    • an ectopic pregnancy
    • after an amniocentesis (blood is taken from the umbilical cord for testing)
    • any other testing that involves blood being taken from the placenta

    In these situations, it is a severe risk if you also have Rh incompatibility (as discussed in point 3). Your body will produce antibodies as an immune response. This can lead to the baby having anaemia and/or jaundice.

    How to Protect Your Baby from Blood Group-Related Problems

    So, in case any of the above pointers hold true for you, what is the solution? A baby’s blood group is usually not known during pregnancy. This is why it is recommended to strictly follow these preventive measures to give birth to a healthy baby:

    Blood Groups and Types

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    The Information Standard

    Dr John Cox, 28 Jan 2016

    In this series

    In this article

    • arrow-downWhat is a blood group?
    • arrow-downHow is blood group testing done?
    • arrow-downBlood transfusions and cross-matching
    • arrow-downBlood groups and pregnancy
    • arrow-downDonating blood

    Blood Groups and Types

    In this article

    The main reasons to know your blood group are if you need to have a blood transfusion or if you are pregnant.

    What is a blood group?

    Red blood cells (erythrocytes) have certain proteins on their surface, called antigens. Also, your plasma contains antibodies which will attack certain antigens if they are present. ABO and rhesus are both types of antigens found on the surface of red blood cells. There are lots of other types but these are the most important.

    ABO blood types

    These were the first type discovered.

    • If you have type A antigens on the surface of your red blood cells, you also have anti-B antibodies in your plasma.
    • If you have type B antigens on the surface of your red blood cells, you also have anti-A antibodies in your plasma.
    • If you have type A and type B antigens on the surface of your red blood cells, you do not have antibodies to A or B antigens in your plasma.
    • If you have neither type A nor type B antigens on the surface of your red blood cells, you have anti-A and anti-B antibodies in your plasma.

    It is not known what the functions of the A and B antigens are. People who don’t have either (blood group O) are still just as healthy. There is some evidence that people of different blood groups may be more or less susceptible to certain diseases – for example, blood clots in the blood vessels (thromboembolism) and malaria. There is no evidence that people with different blood groups should follow different diets.

    Rhesus types

    Most people are ‘rhesus positive’. This means they have rhesus antigens on their red blood cells. But, about 3 in 20 people do not have rhesus antibodies and are said to be ‘rhesus negative’.

    Blood group names

    Your blood group depends on which antigens occur on the surface of your red blood cells. Your genetic make-up, which you inherit from your parents, determines which antigens are present on your red blood cells. Your blood group is said to be:

    • A+ (A positive) if you have A and rhesus antigens.
    • A− (A negative) if you have A antigens but don’t have rhesus antigens.
    • B+ (B positive) if you have B and rhesus antigens.
    • B− (B negative) if you have B antigens but don’t have rhesus antigens.
    • AB+ (AB positive) if you have A, B and rhesus antigens.
    • AB− (AB negative) if you have A and B antigens but don’t have rhesus antigens.
    • O+ (O positive) if you have neither A nor B antigens but you have rhesus antigens.
    • O− (O negative) if you don’t have A, B or rhesus antigens.

    Other blood types

    There are many other types of antigen which may occur on the surface of red blood cells. However, most are classed as ‘minor’ and are not as important as ABO and rhesus.

    How is blood group testing done?

    Basically, a sample of your blood is mixed with different samples of plasma known to contain different antibodies. For example, if plasma which contains anti-A antibodies makes the red cells in your blood (erythrocytes) clump together, you have A antigens on your blood cells. Or, if plasma which contains rhesus antibodies makes the red cells in your blood clump together, you have rhesus antigens on your blood cells. By doing a series of such tests it is possible to determine what antigens are on your red blood cells and therefore determine your blood group.

    Routine blood grouping checks for your ABO and rhesus status. Other red cell antigens are tested for in certain other situations.

    Blood transfusions and cross-matching

    If you have a blood transfusion, it is vital that the blood you receive is well matched (compatible) with your own. For example, if you receive blood from a person who is A positive and you are B positive then the anti-A antibodies in your plasma will attack the red blood cells (erythrocytes) of the donated blood. This causes the red cells of the donated blood to clump together. This can cause a serious or even fatal reaction in your body.

    Therefore, before a blood transfusion is done, a donor bag of blood is selected with the same ABO and rhesus blood group as yourself. Then, to make sure there is no incompatibility, a small sample of your blood is mixed with a small sample of the donor blood. After a short time the mixed blood is looked at under a microscope to see if there has been any clumping of blood. If there is no clumping, then it is safe to transfuse the blood.

    Blood groups and pregnancy

    A blood group test is always done on pregnant women. If the mother is rhesus negative and the unborn baby is rhesus positive (inherited from a rhesus positive father) then the mother’s immune system may produce anti-rhesus antibodies. These may attack and destroy the baby’s blood cells. This is rarely a problem in a first pregnancy. However, without treatment, this can become a serious problem in subsequent pregnancies, as the mother’s immune system will be ‘sensitised’ after the first pregnancy.

    Donating blood

    Giving blood is simple and saves lives. The blood transfusion service needs people of all blood groups to donate blood, but especially if you have one of the rarer blood groups. By donating blood, you will find out what blood group you are.

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