#192 Management of Alloimmunization During Pregnancy Flashcards
What are the five major antigens that can be identified with known typing sera (there are many variant antigens)?
C, c, D, E, and e. No antiserum specific for a “d” antigen, so “d” indicates the absense of an evident allelic product
What are the most common Rh gene complexes in whites (2 )?
CDe/cde and CDe/CDe. Approximately 55% of all whites have a CcDe or CDe phenotype.
Which Rh gene complex has never been demonstrated in vivo?
CdE
Cases of alloimmunization causing transfusion reactions are most often caused by which antigen incompatibility?
D antigen
Cases of alloimmunization causing serious hemolytic disease in the fetus and newborn are most often caused by which antigen incompatibility?
D antigen
Which antigen does Rh positive typically refer to? Rh negative?
D antigen on erythrocytes. Absence of D antigen on erythrocytes
What is weak D positive (re: type and screen results)? What causes it, clinical concerns?
Weak D can be caused by Cw antigen and the Du antigen. Latter is a heterogeneous group of clinically important D antigen variants. Some weak D-pos patients are capable of producing the anti-D antibody, although alloimmunization rarely occurs
What are the most frequently encountered antibodies other than D? (re: blood types)
Lewis (Lea and Leb) and I antibodies
What is the risk of Lewis antibodies in pregnancy? Mechanism.
Low risk. Like most cold agglutinins, Lewis antibody does not cause erythroblastosis fetalis because they are predominantly IgM and poorly expressed on fetal and newborn erythrocytes
What is the risk of I antibodies in pregnancy? Mechanism.
Low risk. Like most cold agglutinins, I antibody does not cause erythroblastosis fetalis because they are predominantly IgM and poorly expressed on fetal and newborn erythrocytes
What is the risk of Kell antibodies in pregnancy? Mechanism.
Can produce erythroblastosis fetalis.
How does Kell autoimmunization occur?
Typically caused by prior transfusion where Kell compatibility was not considered when blood was cross-matched
In cases of pregnancy affected by Kell sensitization, does amniotic fluid analysis correlate to severity of fetal anemia?
Correlates poorly
What % of whites are Rh negative? African Americans? Asians and Native Americans?
Whites: 15%
African Americans: 5-8%
Asians and Native Americans: 1-2%
Among whites, an Rh negative woman has an approximately what % chance of mating with an Rh pos man. What % are heterozygous and what % are homozygous?
85% of mating with Rh positive man. 60% heterozygous. 40% homozygous at D locus.
In what % of births, is there enough fetomaternal hemorrhage sufficient to cause alloimmunization at time of delivery?
15-50% of births
What clinical factors increase the volume of fetomaternal hemorrhage?
Cesarean delivery, multifetal gestation, bleeding placenta previa or abruption, manual removal of placenta, intrauterine manipulation
What volume of fetal blood entering the maternal circulation causes most cases resulting in alloimmunization?
0.1mL or less
What % of cases of Rh alloimmunization are caused by antepartum fetomaternal hemorrhage?
1-2%
What is the risk of fetomaternal hemorrhage in each trimester?
1st - 7%
2nd - 16%
3rd - 29%
Has alloimmunization been reported after ectopic pregnancies?
Yes
Has alloimmunization been reported after threatened abortion?
Yes
Has alloimmunization been reported after chorionic villus sampling?
Yes
Has alloimmunization been reported after pregnancy termination?
Yes
Has alloimmunization been reported after amniocentesis?
Yes
Has alloimmunization been reported after external cephalic version?
Yes
Is Anti-D immune globulin indicated for patients previously sensitized to D?
No
For Rh negative women, when should they be screened for presence of erythrocyte antibodies?
Initial prenatal visit, prior to administration of rhogam at 28wks, postpartum, and at the time of any event in pregnancy
For women with prior pregnancy affected by alloimmunization, is serial titer assessment sufficient for surveillance of fetal anemia?
No.
What is a critical titer (re: alloimmunization)?
Titer that is associated with a significant risk for severe erythroblastosis fetalis and hydrops, (most often between 1:8 and 1:32)
What is next step in management if Rh D titer is 1:4?
Serial titer assessments every 4 wks (if 1:8 or less)
Do levels of Kell antibodies correlate with fetal status?
No
What is the initial step in management of a pregnancy involving an alloimmunized patient?
Determination of paternal erythrocyte antigen status.
If Rh neg, do nothing.
If Rh pos, heterozygous 50% chance of affected; homozygous 100% affected
How do you determine fetal blood antigen type?
Amniocentesis is the primary modality.
Is CVS or amnio recommended for determination of fetal blood antigen type?
Amniocentesis. Larger concern for fetomaternal hemorrhage with CVS
If amniocentesis results Rh neg fetus (in alloimmunized patient), what is next step?
Periodic noninvasive assessment may be warranted given presence of false-negatives (1-3%)
Can fetal D antigen be detected in maternal plasma or serum?
Yes, can be assessed in the 2nd trimester with >99% accuracy.
How was the severity of erythroblastosis in utero historically measured? How is it currently managed?
Previously with spectral analysis at 450nm on amniotic fluid (measuring bilirubin levels). Now, current trend is management with middle cerebral artery Doppler US
At what fetal middle cerebral artery peak systolic velocity is it predictive of moderate or severe annemia?
Above 1.5 times the multiple of the mean for gestational age (sensitivity 100%, false-positive rate of 12%)
What is the cause of most cases of alloimmunization to minor antigens? How common (%) are antibodies to minor antigens in ob patients?
Most cases due to incompatible blood transfusion. Antibodies to minor antigens occur in 1.5-2.5% of OB patients
What is recommended delivery timing in patients with mild fetal hemolysis (alloimmunization)? Severe, requiring multiple invasive procedures?
IOL at 37-38wks, earlier can be considered if fetal pulmonary maturity is documented by amniocentesis. Delivery at 32-34wks after BMZ if last transfusion at 30-32wks; can consider up to 37-38wks if transfusion performed up to 36wks
After what gestational age are middle cerebral artery measurements no longer accurate for monitoring fetal anemia?
After 34-35wks
What method is accurate in predicting the severity of fetal anemia in patients with Kell alloimmunization?
Doppler measurements. Kell antibody titers and spectral analysis of amniotic fluid (bilirubin levels) are not as predictive as with Rh-D sensitization