Download Pathophysiology of Rh incompatibility

Pathophysiology of Rh incompatibility
At the end of session the student should be able
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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
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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
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Father Rh postive group
Mother Rh negative group
Fetus Rh positive group: Problem starts
Rh Blood group Incompatibility
Fetal blood group same as father’s
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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
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Anti-natal
At delivery
Aminocentesis
CVS
Abortion
Ectopic pregnancy
Abdominal trauma during pregnancy
Accidental or in anadvertent Tx
Factors affecting immunization and Severity
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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:
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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
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Identification of father and mother groups
ABO and Rh grouping
Anticipation of problem
Antibody screen
Antibody identification
Antibody titre
Post delivery investigations
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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
䦋 Characteristic
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좈໱
琰茞
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First pregnancy
ABO
Rh
Yes
Rare
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Disease predicted by titers
Yes
Yes
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Antibody IgG
Yes (anti A,B0
Yes (anti-D, etc)
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Bilirubin at birth
Normal range
Elevated
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Anemia at birth
No
Yes
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Phototherapy
Yes
Yes
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Exchange transfusion
Rare
Sometimes
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Intrauterine transfusion
None
Sometimes
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Spherocytosis
Yes
Rare
Beneficial effects of Exchange Tx
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Removal of bilirubin
Removal of sensitized RBCs
Removal of incompatible antibody
Replacement with compatible RBCs
Suppression of erythropoiesis: reduced production of
incompatible RBCs
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