Pathophysiology of Rh incompatibility

At the end of session the student should be able

to

Appreciate 5 major Rh antigens

State the definition & characteristics of HDN
Describe the role of physician in the diagnosis of HDN
Compare & contrast ABO v Rh HDN
List the tests used for detection of fetomaternal hemorrhage
Select the blood group to be used in HDN

HDN
HDN is the destruction of RBCs of the fetus and neonate
by antibodies produced in mother
Sensitization of mother can be from
1. Previous pregnancies/miscarriages
2. Previous Tx
3. During 2nd or 3rd trimester
Can be due to ABO, Rh or other group incompatibilities
Numerous blood group systems
Few are of significant Clinical importance
Two systems are of more practical importance

1. ABO system
2. Rh or rhesus system
Two closely linked genes on Chromosome 1 control the expression
of Rh antigens

1. RHD: For D polypeptide

2. RHCE for either
RHCe, RHcE, RHce, or RHCE polypeptide
D, C, c, E, e: One set of combination on each chromosome
Majority of HDN are of D antigen type

Father Rh postive group

Mother Rh negative group
Fetus Rh positive group: Problem starts
Rh Blood group Incompatibility

Fetal blood group same as fathers

Entry of Rh positive fetal red cells in maternal circulation

Sensitization of mother
Production of Immune IgG:
Only IgG can be transported across placenta
IgG1 & IgG 2 more efficient in crossing placenta
IgA and IgM cannot cross placenta
Mother IgG crosses placenta into fetal circulation
Coating of fetal red cells by maternal IgG
Destruction of fetal RBCs by mother IgG antibodies
9 % chances of immunization if mother Rh neg and fetus
Rh positive: Produce anti-D
1 ml of fetomaternal hemorrhage is sufficient
1.5-1.9 % risk before delivery
Higher risk at delivery

Risk of Rh immunization producing anti-D in

mother

Anti-natal
At delivery
Aminocentesis
CVS
Abortion
Ectopic pregnancy
Abdominal trauma during pregnancy
Accidental or in anadvertent Tx

Factors affecting immunization and Severity

Antigenic exposure: Amount of fetomaternal hemorrhage

minimum 1 ml required to immunize mother
Host factors: ability to produce antibodies in response to
antigenic exposure
Immunoglobulin class: Only IgG. More severe IgG1 & 2
Antibody Specificity:

Common if anti- D, anti D+C, anti-D+E, anti-C, anti-E,

anti-c, anti-e
Influence of ABO group: Co-existing ABO incompatibility
decreases the Rh HDN as the fetal red cells are actively
removed from the circulation

Hemolysis: Due to maternal Ab

1. Immature fetal liver
2. Increased serum bilirubin ( Indirect)
BM compensation for hemolysis: Expands
BM not able to keep pace with hemolysis
Extra-medullary erythropoiesis in liver and spleen
Hepato-Splenomegaly:
Hepatocellular damage--Portal hypertension
Impairment of hepatic function: Hyoproteinemia
Anemia & Hypoproteinemia
1. High cardiac output failure
2. Generalized edema, effusions, ascites etc

Rh sensitization

Erythroblastosis fetalis

First ante-natal visit

Identification of father and mother groups

ABO and Rh grouping
Anticipation of problem
Antibody screen
Antibody identification
Antibody titre

Post delivery investigations

CBC & peripheral smear of baby

Blood group of baby
Direct anti-globulin test of baby
Anti-body identification
Serum T. Bilirubin and Direct bilirubin
Estimation of fetal cells in maternal circulation

Flow cytometry
Kleihauer-Betke test
Maternal smear within 60 min of delivery
treated with acid

Counterstain
Identification of fetal cells
Vol of fetomaternal hemorrhage = Number of fetal cells x maternal
BV
Number of maternal cells

Peripheral smear

Selection of blood
RBCs must be antigenic negative for the respective
antibodies
CMV negative blood
For premature babies, blood should be irradiated to
prevent Tx associated GVHD
Blood should not contain Hb-S
Blood should be PRBC and not older than 7-10 days

Comparison of ABO v Rh HDN

Characteristic

1
First pregnancy

ABO

Rh

Yes

Rare

Disease predicted by titers

Yes

Yes

Antibody IgG

Yes (anti A,B0

Yes (anti-D, etc)

Bilirubin at birth

Normal range

Elevated

Anemia at birth

No

Yes

Phototherapy

Yes

Yes

Exchange transfusion

Rare

Sometimes

Intrauterine transfusion

None

Sometimes

Spherocytosis

Yes

Rare

Beneficial effects of Exchange Tx

Removal of bilirubin
Removal of sensitized RBCs
Removal of incompatible antibody
Replacement with compatible RBCs
Suppression of erythropoiesis: reduced production of
incompatible RBCs
Thanks and wish you all the best