#181 Prevention of Rh D Alloimmunization Flashcards

1
Q

What is the rate of Rh D-negative individuals in North America?

A

15%

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2
Q

What is the risk of stillbirth, neonatal death or brain injury in fetuses affected by Rh hemolytic disease of the newborn in countries without Rh alloimmunization prophylaxis programs?

A

14% are stillborn. One half of live born infants suffer neonatal death or brain injury.

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3
Q

Postpartum administration of Rh D immune globulin reduces the rate of alloimmunization in at-risk pregnancies from what % to what %? What is the risk with additional antepartum administration?

A

From approximately 13-16% to approximately 0.5-1.8%. Risk of 0.14-0.2% with addition of antepartum administration.

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4
Q

What region(s) of the world have the highest prevalence of Rh negative phenotype?

A

European and North American descent (15-17%)

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5
Q

What region(s) of the world have the lowest prevalence of Rh negative phenotype?

A

Asia (0.1-0.3%)

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6
Q

What is alloimmunization?

A

An immunologic reaction against foreign antigens that are distinct from antigens on an individual’s cells

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7
Q

What is fetal-maternal hemorrhage?

A

Term used to identify varying amounts of fetal cells in the maternal circulation from small interruptions at the fetal-maternal placental interface

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8
Q

What events can lead to maternal exposure to fetal RBCs and consequently, Rh D alloimmunization?

A

Miscarriage, ectopic pregnancy, antenatal bleeding, delivery, chorionic villus sampling, amniocentesis, pregnancy-related uterine curettage, surgical treatment of ectopic pregnancy, evacuation of molar pregnancy, therapeutic termination of pregnancy, abdominal trauma, IUFD, external cephalic version

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9
Q

What percent of women with threatened abortion in the first trimester have a fetal-maternal hemorrhage?

A

3-11%

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10
Q

What percent of women giving birth in the third trimester have a fetal-maternal hemorrhage?

A

45%

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11
Q

What volume of fetal-maternal hemorrhage is required to cause Rh D alloimmunization?

A

Can be as small as 0.1mL or as large as 30mL

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12
Q

What is the risk of Rh D alloimmunization in susceptible women after spontaneous miscarriage?

A

1.5-2%

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13
Q

What is the risk of Rh D alloimmunization in susceptible women after D&C?

A

4-5%

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14
Q

What is the risk of fetal-maternal hemorrhage of 0.6mL or more during chorionic villus sampling?

A

14% risk

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15
Q

What is the risk of fetal-maternal hemorrhage with amniocentesis?

A

2-6%, even if placenta not transversed

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16
Q

What is the risk of fetal-maternal hemorrhage with external cephalic version?

A

2-6%

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17
Q

How is anti-D immune globulin (Rhogam) made?

A

Extracted by cold alcohol fractionation from plasma donated by individuals with high-titer anti-D immune globulin G antibodies

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18
Q

300mcg of anti-D immune globulin can prevent Rh D alloimmunization after exposure up to how many mLs of Rh D-positive fetal whole blood versus mLs of fetal red blood cells?

A

30mL of fetal whole blood, 15mL of fetal red blood cells

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19
Q

Asymptomatic fetal-maternal hemorrhage during third trimester triggers alloimmunization in what % of at-risk women before delivery?

A

2%

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20
Q

At what gestational age should you administer anti-D immunoglobulin in at-risk women? What is the dose?

A

300mcg at 28 weeks

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21
Q

What percent of Rh D-negative women will have Rh D negative infants?

A

40%

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22
Q

How often will fetal-maternal hemorrhage at delivery exceed 30mL (ie, mother would need more than standard 300mcg of rhogam)?

A

2-3 per 1,000 deliveries

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23
Q

What should be tested after delivery of Rh D-negative mother in regards to helping prevent alloimmunization?

A

Baby’s Rh status (no need for Rhogam if baby Rh negative). If baby Rh positive, need additional testing to assess the volume of fetal-maternal hemorrhage to guide amount of rhogam to administer

24
Q

What is the routine screening for fetal-maternal hemorrhage (technique of initial screen)? What level does it detect and how does it work?

A

Rosette fetal red blood cell assay. Performed by incubation of maternal blood sample with Rh immunoglobin that will bind fetal Rh D-pos RBCs, followed by addition of enzyme-treated reagent indicator RBCs. Rh D-pos fetal RBCs in mom’s circulation result in forming aggregates (rosettes) that can be visualized by light microscopy. Can detect greater than 2mL of fetal whole blood in maternal circulation

25
Q

What is the follow up test to a positive fetal-maternal hemorrhage (rosette fetal RBC assay)?

A

Method to determine percentage of fetal RBC in maternal circulation, such as Kleihauer-Betke test or flow cytometry.

26
Q

How does the Kleihauer-Betke test work?

A

Relies on the principle that fetal RBCs contain mostly fetal hemoglobin F, which is resistant to acid elution, whereas adult hemoglobin is acid sensitive.

27
Q

What are the downfalls of the Kleihauer-Betke test?

A

Lacks standardization and precision. May not be accurate in medical condition associated with RBCs containing increased % of hemoglobin F, such as sickle cell and thalassemias

28
Q

What is an alternative to Kleihauer-Betke to assessing %fetal blood in maternal circulation? How does it work?

A

Flow cytometry. Uses monoclonal antibodies to hemoglobin F or the Rh D antigen with quantification fluorescence. Highly sensitive and accurate.

29
Q

What is the maximum dose of rhogam you can administer? Can you administer all at once?

A

8 vials, 300mcg x 8 = 2400mcg, which would cover 240mL of fetal blood. Administer IM at separate sites every 12 hours until desired dose reached vs IV form.

30
Q

What are reasons for failure to prevent Rh D alloimmunization?

A

Omission of immune globulin after recognized sensitizing event (41%); administration outside of recommended guidelines (13%), spontaneous immunization despite adherence (0.1-0.2%)

31
Q

What is the catch-22 regarding rhogam and its supply?

A

The more you treat patients with rhogam, the fewer people that will have anti-D immune globulin, which means the fewer amount of rhogam you will be able to get for future patients

32
Q

What are noninvasive ways to determine if Rh negative pregnant women need rhogam?

A
  1. If known FOB, test FOB blood type

2. cell-free DNA (sensitivity greater than 99%, specificity >95%); currently not used due to cost

33
Q

What is the next step if a patient has anti-D antibody at her initial prenatal visit?

A

Obtain further history and investigate to determine whether this is immune mediated or passive (previous injection of anti-D immune globulin)

34
Q

If a patient is Rh D-alloimmunized, do you administer rhogam during pregnancy?

A

No, not beneficial

35
Q

What is the approximate rate of nonpaternity?

A

3%

36
Q

What does it mean when a patients blood type comes back with weak D?

A

80% are associated with weak D type 1, 2, or 3 (which are not associated with risk of alloimmunization), but could be expression of reduced numbers of normal Rh D antigens or express partial or abnormal Rh D antigens (which would convey risk of alloimmunization)

37
Q

How should you treat patients with weak D blood type during pregnancy?

A

Treat like Rh negative and give rhogam as indicated

38
Q

If a patient’s blood is tested and weak D positive, what kind of blood can they receive? What would they be consider if donating blood?

A

They should be categorized as Rh D negative for transfusion, but as Rh D positive if donating blood

39
Q

At what gestational age (how many days from fertilization), has Rh D antigen been reported on fetal erythrocytes?

A

7w3d (38 days from fertilization)

40
Q

Is it recommended to give rhogam to Rh neg pregnant women with threatened abortion prior to 12wks?

A

No recommendation can be made at this time due to insufficient evidence

41
Q

Does the risk of Rh D alloimmunization with evacuation of molar pregnancy change based on type of mole, if yes, how so?

A

Yes. Partial mole has higher risk because embryonic development may cease after erythrocyte production has befun. Complete mole does not undergo organogenesis, and Rh D antigens probably not present on trophoblast cells

42
Q

Should Rh D-negative women undergoing uterine evacuation for molar pregnancy receive rhogam, depending on what type of molar pregnancy?

A

Yes, it is reasonable for all. Although do not expect complete molar pregnancy to cause alloimmunization, but diagnosis depends on pathology and cytogenetic evaluation not available at the time of procedure

43
Q

What is the recommended dose of rhogam in first and second trimesters of pregnancy with pregnancy termination?

A

50-120mcg rhogam prior to 12 wks, 300mcg after 12wks

44
Q

Alloimmunization has been reported to occur in what % of women with ruptured tubal pregnancy?

A

24%

45
Q

Is rhogam recommended for Rh D negative women receiving medical treatment for ectopic pregnancy? Surgical?

A

Yes x 2

46
Q

Is rhogam recommended for Rh D-negative women who experience antenatal hemorrhage after 20 weeks?

A

Yes

47
Q

Is it recommended to repeat antibody screening in patients at 28 weeks gestation prior to rhogam administration?

A

Yes

48
Q

What is the median half-life of rhogam in the third trimester?

A

23 days

49
Q

If a patient delivers within what time frame after a standard rhogam dose, does the patient not require the postnatal dose?

A

If delivery within 3 weeks of standard rhogam administration, in the absence of excessive fetal-maternal hemorrhage

50
Q

Should rhogam be administered to Rh D-negative pregnant patient after abdominal trauma? What additional testing should be done?

A

Yes. Should quantify fetal-maternal hemorrhage to determine the need for additional doses of rhogam

51
Q

Should Rh D-negative pregnant women receive rhogam if experience fetal death in second or third trimester?

A

Yes. Also should quantify fetal-maternal hemorrage to see if additional dosing required

52
Q

How long does anti-d immune globin appear to persist in patients?

A

Approximately 12 weeks

53
Q

Should an Rh D-negative pregnant women receive an additional dose of rhogam if remains undelivered at 40 weeks?

A

Insufficient evidence at this time to make a recommendation. Current consensus guidelines either have no recs or state that a repeat antepartum dose is not generally required

54
Q

Should Rh D-negative women who are undergoing postpartum tubal sterilization candidates for treatment with rhogam?

A

Yes! Can still wind up getting pregnant in future, may need blood transfusion in future.

55
Q

When is the ideal time to administer rhogam after a potentially sensitizing event? How many days postpartum may patients still benefit?

A

Best within 72 hours. Some may still receive benefit as late as 28 days postpartum