- Antibody of RBCs potentially cause HDN is antibody of IgG class that possessed by the mother and the antibody is known could cause various degree of complications to the foetus if the foetus has RBCs containing the corresponding antigen.
- IgG class antibody is important in HDN because their ability to cross placenta and are actively transported cross the placenta.
- Other factors that determine the degree and the incident of HDN are
- Specificity, avidity and class of the antibody
- Maternal antibody titre
- There are three major aetiology of HDN, which are:
- Rh HDN
- ABO HDN
- Other alloantibodies
Rh HDN
- Rh HDN is the most severe form of HDN among the three aetiology of HDN and sometimes fatal.
- Rh HDN happens when mother, who is D negative, bearing D positive foetus.
- D positivity of the foetus is due to genetically inheritance of D from father.
- If the father is heterozygous for the RHD deletion, there is a 50% chance of the foetus being D-negative.
- If the father is homozygous for the RHD gene, the foetus will definitely inherit the D antigen.
- D- mother who lack a functional RHD gene do not produce the D antigen, and may be immunized by D-positive foetal blood.
- Anti-D is the commonest antibody in Rh system that cause HDN and the complication vary from moderate to severe.
- Second most common is anti-E that can cause mild HDN complication.
- Anti-c can range from a mild to severe complication.
- Other two antibodies of Rhesus group (anti-e and anti-C) are rare to be reported.
- Combination of Rhesus antibodies can be severe.
- Sensitization usually occurs very late in Rh-positive pregnancy, hence first Rh-positive child is not affected but the second Rh-positive child will be equally or severely affected.
- However, sensitization at first Rh-positive pregnancy can occur because foetus express Rh antigen on their RBCs membrane after 4 weeks of gestation.
- Anti-D developed usually not detected before week 35 of gestation and the antibody titre is usually low, therefore, first Rh-positive child seldom shows clinically significant HDN.
- Sensitization can occur through of fetomaternal haemorrhage (delivery, placental membrane rupture, trauma to abdomen, amniocentesis, abortion etc.) and previous transfusion of incompatible Rhesus blood group.
- Degree of sensitization varies according to individual (example: immune response) and level of exposure to Rh-positive RBCs.
ABO HDN
- ABO HDN is the most common form of HDN.
- Anti-A and anti-B in person of A and B blood group are mostly of IgM class and cause no isoimmunisation to occur.
- In the other hand, anti-A and anti-B in O blood group person are partially of IgG class.
- Therefore, when O blood group mother is gestating A or B blood group foetus, there is a possibility of HDN to occur.
- ABO HDN can occur in the first pregnancy due to unnecessary need for sensitization since ABO antibodies is readily present in the blood system (natural occurring antibodies).
- ABO HDN has mild complication and RBCs destruction is usually short-live (jaundice and anaemia only evident within 12 to 48 hours after birth).
- This mild complication occurs is may be due to
- Smaller number of A and B antigenic site on foetal RBC membrane
- Foetal RBCs are less developed at birth, hence less RBC destruction by maternal antibodies
- Presence of A and B antigen on other than RBCs surfaces such as tissues and secretions cause the ABO antibodies fractionate to combine with the antigens, therefore less antibodies that cross placenta combine to foetal RBCs
Other alloantibodies
- HDN that caused by other alloantibodies is uncommon.
- Most frequently involved antibodies of Kell, Duffy, Kidd and MNS blood group system.
- Most important is anti-K (after anti-c) that can cause severe HDN (second most common cause of severe HDN after Rh HDN).
- It can happen as early as at 20 weeks of gestation.
- Alloimmunization is more often cause by transfusion rather than fetomaternal hemorrhage itself
- Anti-K 1 antibodies could cause HDN ranges from mild to severe.
- Anti-K 2, anti-K 3 and anti-K 4 antibodies are rare.