1
Q
What is HDFN?
A
Destruction of fetal and neonatal RBCs by antibodies produced by the mother
2
Q
What type antibody is transported across the placenta?
A
IgG
3
Q
What type antibody is NOT transported across the placenta?
A
- IgM
- IgA
4
Q
Mom’s Abs are directed against antigens on the _____. The Newborn D antigen is inherited from ______.
A
- Fetus
- Father
5
Q
What child is unaffected because the mother is not yet immunized?
A
the first born
6
Q
What child is affected because the mother IS immunized?
A
every D positive child born after the first D positive child
7
Q
How does the newborn’s RBCs enter the maternal circulation?
A
at delivery, when the placenta separates from the uterus
8
Q
What happens to the RBCs of a D positive child of a sensitized D negative mom?
A
- Maternal IgG anti-D antibody crosses the placenta
- sensitizes fetal rbc’s
- The fetal rbc’s are then destroyed by the fetal monocyte-macrophage system
- resulting in anemia
9
Q
What does Rhogam do?
A
prevents B-cell activation and memory cell formation
10
Q
What amount of blood can sensitize the mom? (smallest amount)
A
1 mL of blood
11
Q
What can increase the risk of fetal-maternal hemorrhage?
A
- amniocentesis (amniotic fluid removal from the placenta)
- chorionic villous sampling (biopsy of placenta)
- trauma to the abdomen
12
Q
What can cause a significant increase in maternal antibody titers and increase the severity of HDFN?
A
Fetal-maternal hemorrhage
13
Q
What percentage of people ACTUALLY get sensitized (when transfused with 200mL of Rh positive RBC)?
A
85% of people develop anti-D antibodies
14
Q
What is the percentage of Rh negative mothers at risk of immunization after an Rh positive pregnancy?
A
16%
15
Q
What type of IgG is the most efficient in rbc hemolysis? (most dangerous)
A
- IgG-1
- IgG-3
16
Q
What antibody not only destroys circulating rbc’s but also their precursors in the bone marrow and thus suppresses fetal hematopoiesis?
A
Anti-K
17
Q
What antigen is the most immunogenic?
A
D
18
Q
What antigens are potent immunogens?
A
C, E, c
19
Q
What is better Rh incompatibility or ABO AND Rh incompatibility?
A
ABO & Rh incompatibility, (ABO antibodies will destroy the RBCs before the mom can be sensitized with Rh antigens)
20
Q
What causes erythroblastosis fetalis in HDFN?
A
The resultant anemia stimulates fetal bone marrow to produce RBCs at a faster rate even to the point where immature RBCs are released into the circulation
21
Q
What causes hydrops fetalis in HDFN?
A
Severe anemia and hypoproteinemia ( due to decreased protein production by the damaged liver) lead to development of heart failure and generalized edema
22
Q
What is the pathogenesis of HDFN?
A
- Hemolysis occurs when maternal IgG attaches to specific antigens on fetal RBCs (hemolysis)
- The antibody coated cells are removed from the circulation by splenic macrophages (destruction of RBCs)
- The resultant anemia stimulates fetal bone marrow to produce RBCs at a faster rate even to the point where immature RBCs are released into the circulation, hence the term erythroblastosis fetalis (overstimulation of immature RBCs/erythroblasts)
- Severe anemia and hypoproteinemia ( due to decreased protein production by the damaged liver) lead to development of heart failure and generalized edema, a condition known as hydrops fetalis
- The process of RBC destruction continues after birth as long as maternal antibody persists in the infant’s circulation
- IgG has a half-life of 25 days, so hemolysis can continue for days to weeks after delivery
23
Q
What is found in the fetal circulation on a blood smear of a fetus with HDFN?
A
Nucleated RBCs
24
Q
What is the pathogenesis of HDFN with increased bilirubin?
A
- Bilirubin is a metabolic product of hemoglobin break down
- Indirect bilirubin (insoluble) is formed from destruction of fetal rbc’s
- Indirect bilirubin crosses the placenta and is conjugated to direct bilirubin (soluble) by the mother’s liver and then excreted
- After birth, if hemolysis continues, the immature infant’s liver cannot conjugate the bilirubin effectively
- The indirect or unconjugated bilirubin can reach levels of 18-20 mg/dL ( Normal 0.2-1.2 mg/dL)
- The bilirubin can deposit in the infant’s brain causing kernicterus with permanent brain damage
25
How is HDFN diagnosed?
1. During 1st prenatal visit (1st trimester), type and screen and preggo/transfusion history
2. if positive antibody screen, antibody identification is formed
26
Why do Rh negative pregnant women have weakly reactive anti-D antibodies during the third trimester?
due to RhIG received at 28 weeks gestation
( titer is usually <4 )
27
What is used to predict severity of HDFN (particularly Rh and K antibodies)?
antibody titers
28
How do antibody titers work?
1. Mother’s serum or plasma is serially diluted
2. tested against appropriate rbc’s to determine the highest dilution at which an agglutination reaction occurs, using the IAT phase and an anti-IgG reagent
3. The result is expressed as the reciprocal of the titration endpoint or as the titration score
29
What type of reagent RBCs do you use for antibody titers?
homozygous for the antigen
30
What should you do with the first serum/plasma specimens (from antibody titers)?
The first serum or plasma specimens should be frozen and run in parallel with later specimens
31
What number of dilutions are considered significant?
>2
32
How many dilutions are considered critical titer for Rh antibodies?
16
33
How many dilutions are considered critical titer for Kell antibodies?
8
34
What is Cordocentesis?
Using ultrasound, a needle is inserted into the umbilical vein and a sample of fetal blood is obtained to test for hemoglobin, hematocrit, DAT
35
What level of hemoglobin from Cordocentesis is considered Severe anemia?
<7 g/dL
36
How Do You Know You Have Fetal Blood?
Must test MCV to insure you have fetal blood
MCV (mean corpuscular volume) is much higher in fetuses and newborns than in adults since their rbc’s are larger
37
Why Blood < 7 Days Old for fetuses?
2,3 DPG- (2,3 diphosphoglycerate) is formed as a result of glycolysis; level in stored rbc’s is lost fairly rapidly, within about a week
adults will regenerate 2,3 DPG within 12-24hrs; babies won't
38
Why Sickle Negative Blood for fetuses?
Oxygen won't flow right w/ sickle positive blood
want to give the fetus the most oxygen possible
39
What is Phototherapy?
It is a treatment for fetuses with high bilirubin levels,
Conjugates bilirubin and thus allows it to be excreted
40
What are the guidelines for HDNF fetuses that exchange transfusions?
1. After birth, removes maternal antibody and bilirubin
2. Replaces sensitized rbc’s with compatible donor rbc’s
3. Uses reconstituted whole blood (mix donor rbc’s with fresh frozen plasma to get a Hct of 45-50%)
4. Blood must meet same criteria as described for intrauterine transfusions, except for hematocrit
41
What is the "blocking phenomenon"
1. Testing for D antigen may be falsely negative.
2. If large amounts of maternal anti-D antibody are attached to the baby’s D antigen,- there is no room for the reagent anti-D to bind– termed the blocking phenomenon
42
When would you suspect the fetus has the "blocking phenomenon"?
1. suspect when baby types as D negative
2. the DAT is positive
3. mother has an anti-D antibody
43
What do you do if you think the fetus has "the blocking phenomenon"?
perform an eluate to demonstrate the anti-D
44
What type of blood is used for Serologic Testing of Newborn?
cord blood
45
What is typed during Serologic Testing of Newborn?
ABO front type ONLY (ABO, Rh, and weak D)
46
How does RhIG work? (Rhogam or Rh Immune globulin)
1. Concentrate of IgG anti-D antibody that prevents active immunization induced by a foreign D antigen
2. Attaches to fetal Rh positive rbc’s in the maternal circulation
3. The coated rbc’s are then removed by the macrophages in the maternal spleen before the mother can become immunized to the D antigen
4. Antenatal dose is given at 28 weeks gestation to Rh negative mothers provided they do not have an anti-D alloantibody
5. Causes only a titer of 1 or 2 in the mother but may cause a + DAT in the newborn
47
What is the half-life of RhIG?
1. 25 days
48
What percentage of the antenatal dose is present at 40 weeks gestation?
10%
49
What is the standard dose of RhIG?
300 μg
50
300 μg of RhIG suppresses how many mL of RBC? whole blood?
1. 15mL of RBCs (from transfusion)
2. 30mL of whole blood (fetal maternal bleed)
51
When would you administer a microdose (50 μg)?
fetal maternal bleeds prior to 12 weeks gestation
(e.g. from miscarriages, ectopic pregnancies, etc.)
52
What is rosette test?
1. Fetal Screen for Fetal-Maternal Hemorrhage
2. A maternal sample is obtained after delivery that is screened for fetal-maternal hemorrhage
53
What is a Qualitative test for FMH (fetal-maternal hemorrhage)?
Rosette test
54
What do you do if the rosette test is positive?
FMH must be quantified using a Kleihauer-Betke test or flow cytometry
55
How do you do a rosette test?
1. A maternal sample is incubated with anti-D antibody; then D positive indicator cells are added
2. Indicator rbc’s then form agglutinates (rosettes) around Rh + fetal rbc’s
3. Anti-D reagent attaches to D positive baby RBCs
4. D positive indicator cells then attach to the anti-D forming rosettes which are observed and counted microscopically
56
What is the Kleihauer-Betke Test?
1. Quantifies FMH so as to determine the adequate dose of RhIG to be given
2. Usually maternal samples are postpartum samples
3. Occasionally during pregnancy there is trauma to the abdomen; a KB test is performed to detect FMH and perhaps if positive then a need for intervention
57
How do you do a Kleihauer-Betke Test?
1. Maternal blood is treated with an acid which denatures HgA (maternal hemoglobin) but does not denature HgF (fetal or newborn hemoglobin)
2. A counter stain is added in order to stain the fetal cells; maternal cells appear as ghosts
58
What is the formula for FMH Volume (Whole blood)
1. FMH Volume (Whole blood) = # fetal cells x maternal blood volume (total cell count) ???
2. Fetal Cell % x 50 = FMH Volume
(fetal cell count ex. 6 fetal cells out of 2000 (always 2k) = .3%)
59
How Much RhIG to Give?
1. FMH volume / 30 (then round to whole number)
2. add 1 extra dose of RhIG (imprecise method)
3. if abdominal trauma or invasive procedure (amniocentesis, chorionic villi sampling, etc.), give RhIG even if given antenatal dose already
60
What is the most common HDFN?
ABO HDFN
61
What is ABO HDFN?
1. ABO incompatibility between mother and newborn
2. Involves group O mothers (anti-A,B antibody in group O is an IgG) with Group A, B, AB newborn
3. Severe anemia is very rare
62
What antibodies are caused by ABO HDFN?
IgG (only one that can cross placenta)
63
Can ABO HDFN occur in the first pregnancy?
yes
64
What is the platelet equivalent to HDFN?
Neonatal Alloimmune Thrombocytopenia (NAIT)
65
What is the most common antibody implicated with Neonatal Alloimmune Thrombocytopenia (NAIT)?
1. anti-human platelet antigen-1 (HPA-1)
1a. old term is PLA-1
2a. (present in 98% of the population)
66
What disease has a High rate of intracranial hemorrhage?
Neonatal Alloimmune Thrombocytopenia (NAIT)
67
What happens if Neonatal Alloimmune Thrombocytopenia (NAIT) antibodies develop during the first pregnancy?
1. affects the first pregnancy
2. subsequent pregnancies are also affected to the same severity or worse
3. Usually not discovered until birth when baby presents with bleeding
68
What is the treatment for Neonatal Alloimmune Thrombocytopenia (NAIT) ?
1. steroids
2. IVIG
69
More info abt Neonatal Alloimmune Thrombocytopenia (NAIT)
1. Fetal blood sampling with intrauterine platelet transfusion with antigen-negative platelets if count < 50,000
2. Mother is often the source of the antigen-negative platelets for transfusion to the baby
3. Affected babies usually delivered by C-section
4. After delivery, greatest risk for bleeding is within 96 hours; platelet count of 50-100,000 should be maintained
5. Thrombocytopenia may persist for 8-12 weeks
BMS 185 Lecture
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