#192 Management of Alloimmunization During Pregnancy

Question 1

What are the five major antigens that can be identified with known typing sera (there are many variant antigens)?

Answer 1

C, c, D, E, and e. No antiserum specific for a “d” antigen, so “d” indicates the absense of an evident allelic product

Question 2

What are the most common Rh gene complexes in whites (2 )?

Answer 2

CDe/cde and CDe/CDe. Approximately 55% of all whites have a CcDe or CDe phenotype.

Question 3

Which Rh gene complex has never been demonstrated in vivo?

Answer 3

CdE

Question 4

Cases of alloimmunization causing transfusion reactions are most often caused by which antigen incompatibility?

Answer 4

D antigen

Question 5

Cases of alloimmunization causing serious hemolytic disease in the fetus and newborn are most often caused by which antigen incompatibility?

Answer 5

D antigen

Question 6

Which antigen does Rh positive typically refer to? Rh negative?

Answer 6

D antigen on erythrocytes. Absence of D antigen on erythrocytes

Question 7

What is weak D positive (re: type and screen results)? What causes it, clinical concerns?

Answer 7

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

Question 8

What are the most frequently encountered antibodies other than D? (re: blood types)

Answer 8

Lewis (Lea and Leb) and I antibodies

Question 9

What is the risk of Lewis antibodies in pregnancy? Mechanism.

Answer 9

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

Question 10

What is the risk of I antibodies in pregnancy? Mechanism.

Answer 10

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

Question 11

What is the risk of Kell antibodies in pregnancy? Mechanism.

Answer 11

Can produce erythroblastosis fetalis.

Question 12

How does Kell autoimmunization occur?

Answer 12

Typically caused by prior transfusion where Kell compatibility was not considered when blood was cross-matched

Question 13

In cases of pregnancy affected by Kell sensitization, does amniotic fluid analysis correlate to severity of fetal anemia?

Answer 13

Correlates poorly

Question 14

What % of whites are Rh negative? African Americans? Asians and Native Americans?

Answer 14

Whites: 15%
African Americans: 5-8%
Asians and Native Americans: 1-2%

Question 15

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?

Answer 15

85% of mating with Rh positive man. 60% heterozygous. 40% homozygous at D locus.

Question 16

In what % of births, is there enough fetomaternal hemorrhage sufficient to cause alloimmunization at time of delivery?

Answer 16

15-50% of births

Question 17

What clinical factors increase the volume of fetomaternal hemorrhage?

Answer 17

Cesarean delivery, multifetal gestation, bleeding placenta previa or abruption, manual removal of placenta, intrauterine manipulation

Question 18

What volume of fetal blood entering the maternal circulation causes most cases resulting in alloimmunization?

Answer 18

0.1mL or less

Question 19

What % of cases of Rh alloimmunization are caused by antepartum fetomaternal hemorrhage?

Answer 19

1-2%

Question 20

What is the risk of fetomaternal hemorrhage in each trimester?

Answer 20

1st - 7%
2nd - 16%
3rd - 29%

Question 21

Has alloimmunization been reported after ectopic pregnancies?

Answer 21

Yes

Question 22

Has alloimmunization been reported after threatened abortion?

Answer 22

Yes

Question 23

Has alloimmunization been reported after chorionic villus sampling?

Answer 23

Yes

Question 24

Has alloimmunization been reported after pregnancy termination?

Answer 24

Yes

Question 25

Has alloimmunization been reported after amniocentesis?

Answer 25

Yes

Question 26

Has alloimmunization been reported after external cephalic version?

Answer 26

Yes

Question 27

Is Anti-D immune globulin indicated for patients previously sensitized to D?

Answer 27

No

Question 28

For Rh negative women, when should they be screened for presence of erythrocyte antibodies?

Answer 28

Initial prenatal visit, prior to administration of rhogam at 28wks, postpartum, and at the time of any event in pregnancy

Question 29

For women with prior pregnancy affected by alloimmunization, is serial titer assessment sufficient for surveillance of fetal anemia?

Answer 29

No.

Question 30

What is a critical titer (re: alloimmunization)?

Answer 30

Titer that is associated with a significant risk for severe erythroblastosis fetalis and hydrops, (most often between 1:8 and 1:32)

Question 31

What is next step in management if Rh D titer is 1:4?

Answer 31

Serial titer assessments every 4 wks (if 1:8 or less)

Question 32

Do levels of Kell antibodies correlate with fetal status?

Answer 32

No

Question 33

What is the initial step in management of a pregnancy involving an alloimmunized patient?

Answer 33

Determination of paternal erythrocyte antigen status.
If Rh neg, do nothing.
If Rh pos, heterozygous 50% chance of affected; homozygous 100% affected

Question 34

How do you determine fetal blood antigen type?

Answer 34

Amniocentesis is the primary modality.

Question 35

Is CVS or amnio recommended for determination of fetal blood antigen type?

Answer 35

Amniocentesis. Larger concern for fetomaternal hemorrhage with CVS

Question 36

If amniocentesis results Rh neg fetus (in alloimmunized patient), what is next step?

Answer 36

Periodic noninvasive assessment may be warranted given presence of false-negatives (1-3%)

Question 37

Can fetal D antigen be detected in maternal plasma or serum?

Answer 37

Yes, can be assessed in the 2nd trimester with >99% accuracy.

Question 38

How was the severity of erythroblastosis in utero historically measured? How is it currently managed?

Answer 38

Previously with spectral analysis at 450nm on amniotic fluid (measuring bilirubin levels). Now, current trend is management with middle cerebral artery Doppler US

Question 39

At what fetal middle cerebral artery peak systolic velocity is it predictive of moderate or severe annemia?

Answer 39

Above 1.5 times the multiple of the mean for gestational age (sensitivity 100%, false-positive rate of 12%)

Question 40

What is the cause of most cases of alloimmunization to minor antigens? How common (%) are antibodies to minor antigens in ob patients?

Answer 40

Most cases due to incompatible blood transfusion. Antibodies to minor antigens occur in 1.5-2.5% of OB patients

Question 41

What is recommended delivery timing in patients with mild fetal hemolysis (alloimmunization)? Severe, requiring multiple invasive procedures?

Answer 41

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

Question 42

After what gestational age are middle cerebral artery measurements no longer accurate for monitoring fetal anemia?

Answer 42

After 34-35wks

Question 43

What method is accurate in predicting the severity of fetal anemia in patients with Kell alloimmunization?

Answer 43

Doppler measurements. Kell antibody titers and spectral analysis of amniotic fluid (bilirubin levels) are not as predictive as with Rh-D sensitization