Alloimmunization/ Hydrops

Question 1

The prevalence of red cell alloimmunization (in general) in pregnancy approximates

Answer 1

1%

Question 2

Minimal amount that may cause sensitization

Answer 2

As little as 0.1 ml of fetal erythrocytes

Question 3

Responsible genes for D antigen

Answer 3

2 genes
RHD And RHCE
Are located on the short arm of chromosome 1 and are inherited together.

Question 4

The prevalence of D alloimmunization complicating pregnancy ranges from

Answer 4

0.5 to 0.9 percent.

Question 5

Without anti-D prophylaxis, D-negative woman delivered of D-positive, ABO-compatible newborn has —% likelihood of developing alloimmunization.

Answer 5

16%
(2% at the time of delivery
7% by 6 min postpartum
And the remaining 7% will be stabilized) —producing detectable antibodies only in a subsequent pregnancy (Bowman, 1985).

Question 6

Without anti-D prophylaxis, D-negative woman delivered of D-positive, ABO-INcompatible newborn has —% likelihood of developing alloimmunization.

Answer 6

2%

Question 7

Sensitization to E, c and C antigens complicates approximately —% of pregnancies and accounts for about —% of red cell alloimmunization cases.

Answer 7

0.3%, 30%
(The most common is anti-E alloimmunization, but the need for fetal or neonatal transfusions is greater with anti-c alloimmunization than with anti-E or anti-C.

Question 8

The most common cause of haemolytic disease of newborn

Answer 8

Incompatibility for the major blood group antigens A and B.

Question 9

An estimated — to — % of foetuses from D-alloimmunized pregnancies will have mild to moderate haemolytic anaemia.

Answer 9

An estimated 25 to 30 % of foetuses from D-alloimmunized pregnancies will have mild to moderate haemolytic anaemia. And without treatment up to 25% will develop hydrous.

Question 10

Intra-uterine Fetal transfusion complications

Answer 10

Fetal death (2 %)
Emergency caesarean (1%)
Infection and PPROM(0.3% for each)
Stillbirth (exceeds 15% if transfusion required before 20wks)

Question 11

Overall survival rate of hydrops foetuses treated by Intra-Uterine Fetal blood transfusion

Answer 11

Approached 75-80 %
(Among 2/3 with resolution of hydrops following transfusion more than 95% survived, the survival rate was <40% if hydrops persisted.

Question 12

What percent of alloimmunization occurs at the time of delivery?

Answer 12

90%

Question 13

Routine postpartum administration of anti-D to at risk pregnancies within 72 hrs of delivery reduce the alloimmunization by

Answer 13

90%

Question 14

Provision of anti-D Immunoglobulin at 28 wks reduce the 3rd trimester alloimmunization rate from approximately

Answer 14

2% to 0.1%

Question 15

2 to 3 per 1000 pregnancies estimated their fetomaternal hge exceeds 30 ml of whole blood (15 of fetal RBCs) so single dose of Anti-D not sufficient, for this reason all D-negative women should be screened at delivery with

Answer 15

rosette test
( if positive to be followed by Quantitative test like kleihauer-Betke or flow cytometry tests

Me: All ? Is it Cost effective ?

Question 16

The two responsible genes—RHD and RHCE —are located on the — arm of chromosome – and are inherited together, independent of other blood group genes.

Answer 16

The two responsible genes—RHD and RHCE —are located on the short arm of chromosome 1 and are inherited together, independent of other blood group genes.

Question 17

D-negative individuals may become sensitized after a single exposure to as little as – mL of fetal erythrocytes (Bowman, 1988).

Answer 17

D-negative individuals may become sensitized after a single exposure to as little as 0.1 mL of fetal erythrocytes (Bowman, 1988).

Question 18

the American College of Obstetricians and Gynecologists (2019a) has recommended that antibody titers not be used to monitor Kell-sensitized pregnancies. Why?

Answer 18

because Kell antibodies attach to erythrocyte precursors in the fetal bone marrow and thereby impair the normal hemopoietic response to anemia. With fewer erythrocytes produced, there is less hemolysis, and thus severe anemia may not be predicted by the maternal Kell antibody titer.

Question 19

Incompatibility for the major blood group antigens A and B is the most common cause of hemolytic disease in newborns, but it does not cause appreciable hemolysis in the fetus. Why ?

Answer 19

This is because most anti-A and anti-B antibodies are IgM types and do not cross the placenta. Also, fetal red cells have fewer A and B antigenic sites than adult cells and are thus less immunogenic. Approximately 20 percent of newborns have ABO blood group incompatibility, although only 5 percent are affected clinically. In such cases, the resulting anemia is typically mild.

Question 20

Of fetuses from D-alloimmunized pregnancies, – to – percent will have mild to moderate hemolytic anemia, and up to – percent have anemia severe enough to cause hydrops

Answer 20

Of fetuses from D-alloimmunized pregnancies, 25 to 30 percent will have mild to moderate hemolytic anemia, and up to 25 percent have anemia severe enough to cause hydrops

Question 21

If alloimmunization is detected and the titer is below the critical value, the titer is generally repeated every – weeks for the duration of the pregnancy (American College of Obstetricians and Gynecologists, 2019a).

Answer 21

If alloimmunization is detected and the titer is below the critical value, the titer is generally repeated every 4 weeks for the duration of the pregnancy (American College of Obstetricians and Gynecologists, 2019a).

Question 22

amnestic response ? Interesting

Answer 22

If a woman is sensitized from a prior pregnancy, her antibody titer may rise during the current pregnancy even if the current fetus is D-negative because of an amnestic response.

Question 23

With immunoprophylaxis, however, the alloimmunization risk may be reduced to — percent. Despite long-standing and widespread use, its mechanism of action is not completely understood.

Answer 23

<0.2

Question 24

Fetomaternal hemorrhage at delivery accounts for as many as – percent of alloimmunization cases. Routine postpartum administration of anti-D immune globulin to at-risk pregnancies within 72 hours of delivery lowers the alloimmunization rate by – percent (Bowman, 1985).

Answer 24

90 , 90

Question 25

Additionally, provision of anti-D immune globulin at 28 weeks’ gestation reduces the third-trimester alloimmunization rate from approximately 2 percent to – percent (Bowman, 1988). Whenever there is doubt whether to give anti-D immune globulin, it should be given. If not needed, it will not cause harm, but failure to provide it when needed may have severe consequences.

Answer 25

0.1

Question 26

Depending on the preparation, the half-life of anti-D immune globulin ranges from – to – days, which is why it is given both in the third trimester and following delivery.

Answer 26

16 to 24 days

Question 27

The standard intramuscular dose of anti-D immune globulin—300 μg or 1500 IU—will protect the average-sized mother from a fetal hemorrhage of up to – mL of fetal whole blood or – mL of fetal red cells.

Answer 27

The standard intramuscular dose of anti-D immune globulin—300 μg or 1500 IU—will protect the average-sized mother from a fetal hemorrhage of up to 30 mL of fetal whole blood or 15 mL of fetal red cells.

Question 28

A single dose of anti-D immune globulin would be insufficient in such situations. If additional anti-D immune globulin is considered only for women with risk factors, half of those who require additional immune globulin may be missed. For this reason, all D-negative women should be screened at delivery, typically with a rosette test, followed by quantitative testing if indicated (American College of Obstetricians and Gynecologists, 2019b).

Answer 28

The rosette test is a qualitative test that identifies whether fetal Dpositive cells are present in the circulation of a D-negative woman. A sample of maternal blood is mixed with anti-D antibodies that coat any Dpositive fetal cells present in the sample. Indicator red cells bearing the Dantigen are then added, and rosettes form around the fetal cells as the indicator cells attach to them by the antibodies. Thus, if rosettes are visualized, there are fetal D-positive cells in that sample. In the setting of D incompatibility, or any time a large fetomaternal hemorrhage is suspected— regardless of antigen status, a Kleihauer-Betke test or flow cytometry test are used.

Question 29

There are also two scenarios in which the KB may be inaccurate:

Answer 29

(1) maternal hemoglobinopathies in which the fetal hemoglobin level is elevated, such as β-thalassemia, and (2) at or near term, because the fetus may already be producing hemoglobin A.

Flow cytometry is an automated test that can analyze a greater number of cells than the KB test. It is also unaffected by maternal levels of fetal hemoglobin and by fetal levels of hemoglobin A. Flow cytometry has been reported to be more sensitive and accurate than the KB test, however, it uses specialized technology not routinely available in many hospitals

Question 30

Most common Etiology of Nonimmune Hydrops Fetalis

Answer 30

Cardiovascular (21%)

Question 31

Hydrops definition

Answer 31

Hydrops is diagnosed by identifying two or more fetal effusions— pleural, pericardial, or ascites—or one effusion plus anasarca (Fig. 18-4). Sonographically measured skin thickness of >5 mm constitutes edema or anasarca. Placentomegaly is defined as placental thickness ≥4 cm in the second trimester or ≥6 cm in the third trimester (Bellini, 2009; Society for Maternal–Fetal Medicine, 2015b).

Question 32

At least – percent of cases of hydrops are nonimmune (Bellini, 2012)

Answer 32

At least 90 percent of cases of hydrops are nonimmune (Bellini, 2012)

Question 33

Of prenatally diagnosed non-immune hydrops cases, aneuploidy accounts for approximately – percent, cardiovascular abnormalities for – percent, and infections for – percent— the most common of which is parvovirus B19 (Santo, 2011; Sileo, 2020; Sparks, 2019).

Answer 33

Of prenatally diagnosed cases, aneuploidy accounts for approximately 20 percent, cardiovascular abnormalities for 15 percent, and infections for 14 percent— the most common of which is parvovirus B19 (Santo, 2011; Sileo, 2020; Sparks, 2019).

Question 34

Fetal deaths and stillbirths are common with nonimmune hydrops. Overall, only – percent of affected pregnancies result in a liveborn neonate, and of these, the neonatal survival rate is just – percent (Nassr, 2018; Yeom, 2015).

Answer 34

Fetal deaths and stillbirths are common with nonimmune hydrops. Overall, only 40 percent of affected pregnancies result in a liveborn neonate, and of these, the neonatal survival rate is just 50 percent (Nassr, 2018; Yeom, 2015).

Question 35

In multifetal gestations, —– is the most frequent cause of non-immune hydrops (Yeom, 2015).

Answer 35

In multifetal gestations, twin-twin transfusion syndrome is the most frequent cause (Yeom, 2015).

Question 36

When nonimmune hydrops presents before 24 weeks’ gestation, the most frequent aneuploidy is —-, and in such cases, the survival rate is <– percent (Sohan, 2001).

Answer 36

When nonimmune hydrops presents before 24 weeks’ gestation, the most frequent aneuploidy is 45,X—Turner syndrome, and in such cases, the survival rate is <5 percent (Sohan, 2001).

Question 37

initial evaluation of case of non-immune hydrops includes the following:

Answer 37

1. Indirect Coombs test to identify alloimmunization
2. Detailed ultrasound examination of the fetus and placenta that includes: • A detailed anatomical survey to assess for the structural abnormalities • Fetal echocardiography to further evaluate cardiac structure and function • MCA Doppler peak systolic velocity to assess for fetal anemia
3. Amniocentesis to obtain samples for chromosomal microarray analysis or karyotyping and for parvovirus B19, cytomegalovirus, and toxoplasmosis testing,
4. Kleihauer-Betke test to detect fetomaternal hemorrhage if anemia is suspected, depending on findings and test results
5. Consideration of testing for alpha-thalassemia and/or inborn errors of metabolism.