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I. PATHOPHYSIOLOGY OF Rh ISOIMMUNIZATION
A. Race classification: Fisher
1. Rh locus: dD, cC, eE
2. Rh-positive
a. Presence of D
b. d has not been identified (whites 85% Rh-positive; homozygous 45%)
B. Ethnic distribution
1. Basques (Spain): 35% Rh-negative
2. Whites: 15% Rh-negative
3. Blacks: 8% Rh-negative
4. Native Americans: 1-2% Rh-negative
5. Asians: 2% Rh-negative
C. Etiology of blood group immunization
1. Transfusion of improperly cross matched blood products
2. Fetal-maternal transplacental hemorrhage (TPH)
a. TPH occurs in 50 % of deliveries
b. Time of exposure
D. Rh immune response
1. Rh-positive cells enter circulation of Rh-negative person
2. Primary response of anti-D IgM followed by IgG
3. Secondary response of anti-D IgG to repeat Rh-positive exposure
4. Immunization is dose-dependent
E. Incidence of Rh isoimmunization prior to RHIgG (RhoGAM)
Rh and antibody (ABO) status of fetus
1. Rh-positive ABO-compatible: 16% sensitized a. Antepartum: 1.5-2% b. Postpartum: 7% c. Sensitization: 7%
2. Rh-positive ABO incompatible: 1.5-2% sensitized
Pathogenesis of Fetal Anemia (Erythroblastosis Fetalis)
A. Mechanism of RBC destruction
1. Maternal anti-D IgD crosses placenta
2. Anti-D IgG attaches to Rh antigen on fetal RBCs
3. Noncomplement-mediated hemolysis (macrophage attack, causing cell wall
defects and rosette formation)
4. Fetal anemia results in extramedullary erythropoiesis
5. Hepatic erythropoiesis results in
a. Hypoproteinemia (decreased colloid osmotic pressure)
b. Portal hypertension (distortion of hepatic parenchyma)
6. Fetal anemia may cause hypoxia and capillary leak
7. Combination of above (5 and 6) may result in hydrops fetalis
B. Classification of severity
1. Mild (mild jaundice, no anemia): 50%
2. Moderate (moderate anemia, severe jaundice): 25% (10% of affected
neonates had kernicterus without treatment)
3. Severe (hydrops fetalis): 25%
PREVENTION OF Rh Isoimmunization
A. Rh immune globulin
1. Mechanism of action
2. Timing of administration
3. Dosage
a. North America vs Europe
b. IM vs IV
B. Indications for Rh immune globulin administration
1. Abortion (first and second trimester)
2. Ectopic pregnancy
3. Chorionic villus sampling
4.Amniocentesis
5.Antepartum (all Rh-negative mothers unless father of fetus is Rh negative)
6.External cephalic version
7.Postpartum (if neonate is Rh-positive)
C. Rh immune globulin prophylactic failures
1. Failure to administer when indicated (see above)
2. Failure to administer adequate dosage (massive transplacental transfusion)