Rh FACTOR What does Rh refers to?

o Rh is the most important blood group system after ABO in transfusion medicine.

o One of the most complex of all RBC blood group systems with more than 50 different Rh antigens.

o The genetics, nomenclature and antigenic interactions are unsettled.

o There are two genes, RHD and RHCE

RHD: What does the term D-positive and

D-negative refers to?o If Protein (D antigen) is present on the surface of Red blood

cell, the blood will be termed as D-positive.

o If Protein (D antigen) is absent on the surface of Red blood cell, the blood will be termed as D-negative.

RHCE: Four additional antigens: C, c, E, e:o The RhCE protein encodes the C/c antigen (in the 2nd

extracellular loop) and the E/e antigen (in the 4th extracellular loop).

PROTEINS WITH UNKNOWN

FUNCTIONS:o The RhD and RhCE proteins are both transmembrane, multipass proteins that are integral to the RBC membrane.

o Unlike most cell surface molecules, the Rh proteins are not glycosylated (they do not contain oligosaccharides) but they are closely associated with a RBC membrane glycoprotein called RhAG.

o The function of the Rh-RhAG complex might involve transporting ammonium or carbon dioxide. The RhD protein encodes the D antigen.

BACKGROUND INFORMATION: History:

o In 1939, a mother who had just given birth to a still-born child needed a blood transfusion. The ABO blood group system had been discovered almost 40 years previously, and the

importance of giving an ABO-compatible blood transfusion was well established. However, although the mother was transfused with ABO compatible blood from her husband, she still experienced an adverse reaction to the transfusion.

o Her serum was found to contain antibodies that agglutinated her husband's RBCs, even though they were ABO compatible. During the pregnancy, the mother had been exposed to an antigen on the fetal RBCs that was of paternal origin.

o Her immune system attacked this antigen, and the destruction of the fetal RBCs resulted in fetal death. The mother re-

encountered the same paternal antigen when she received a blood transfusion from her husband.

o This time her immune system attacked the transfused RBCs, causing a hemolytic transfusion reaction.

o The antibodies responsible led to the discovery of the Rh blood group.

Landsteiner and Wiener:o Rh system IDENTIFIED by Landsteiner and Wiener in 1940.o Immunized animals to Rhesus macaque monkey RBCs.o Antibody agglutinated 100% of Rhesus and 85% of human

RBCs.o Reactivity paralleled reactivity of sera in women who

delivered infant suffering from hemolytic disease.

Clinical Significance:

o The Rh antigens are highly immunogenic, and most of the Rh antibodies should be considered as potential causes of

hemolytic transfusion reactions and HDN.

o D antigen, after A and B, is the most important RBC antigen in transfusion practice.

o Has been reported that 80%> of D neg individuals who receive single unit of D pos blood can be expected to develop immune anti-D.

o Rh antibodies rarely, if ever, bind complement, and therefore RBC destruction is mediated almost exclusively via macrophages in the spleen (extravascular hemolysis).

Clinical Significance:

o Transfusion reactions :

1. Routine blood typing for Rh D status in both blood donors and transfusion recipients has reduced the incidence of transfusion reactions caused by anti-D.

2. But sensitization to other Rh antigens can be a problem in transfusion medicine, particularly in patients with sickle cell anemia (SCA).

3. SCA is more common in Blacks, and the treatment of SCA involves blood transfusions.