Fetal anemia

Report
ISOIMMUNISATION
William 2001
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Fetal anemia
Fetomaternal hemorrhage
Isoimmunisation
Immune hydrops
Management
Pervention
Large fetomaternal Hge
FETAL ANEMIA
Normal fetal Hb% > 35 weeks = 17 gm/dL
Fetal anemia = < 14 gm/dL
Causes:
 Placenta cut or torn
 Fetal vessel perforation
 Raising the neonate above the abdomen
of his mother before clamping the cord
Delayed clamping of the cord  ↑ of
fetal Hb by 20%
FETAL-TO-MATERNAL HEMORRHAGE
Common in all pregnancies
Rarely > 30mL = 0.3 – 0.6%
Benefit in fetal karyotyping
Keihauer – Batke test:
Identify fetal RBCs by acid elusion
 darker than maternal RBCs
Rosette test:
Maternal blood + anti D Ab+ indicator
 fetal blood surrounded by Abs
More accurate in hemoglobinopathy
Severe anemia  sinusoidal FHR
not pathognomonic 
evaluate immediately
Chronic anemia may  normal FHR
Significant acute /chronic Hge may
 Neurological impairment due to:
Hypotension  ↓ perfusion 
Ischemia
 CNS infarction
Obstetric management may not
improve CNS damage
Large fetal Hg may  fetal death
in 5% and the cause may be unknown
e.g. chorioangioma
Placental abruption :
usually  mild Hg
except if traumatic
Quantification of volume of blood loss:
 influence management
 Determine the dose of Anti D Ig
Fetal red cells =
maternal Hct
X maternal blood volume
X % of fetal cells in Kleihauer
- Batke test ÷ neonatal Hct
Causes of fetal-to-maternal Hg:
 Early abortion
 Elective abortion
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Ectopic
Amniocentesis
Cordocentesis
Chorionic villous sampling
Antepartum trauma
Placental abruption
Fetal demise
Manual placental extraction
External version
ISOIMMUNISATION
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ABO blood group
CDE blood group
Other blood groups
Kell antigen
Other antigens
History:
1892 Ballantin  hydrops fetalis
1932 Anemia and reticulosis are
present in hydrops fetalis
1940 Landsteiner & Weiner
 Rh factor
1941 Levein  hydrops is caused
by maternal isoimmunisation
by Rh –ve fetus
1961 Anti Rh
- Fetal blood contain > 400 Ags
most of them are insignificant
- Most people inherit at least 1 Ag
from their fathers that is lacking
in their mothers
- Isoimmunisation of an Rh –ve
pregnant woman occur as a
result of:
Rh +ve fetus
Blood transfusion
Isoimmunization is rare because:
 Variable Ag amounts
 Variable antigenicity
 Maternal immune respond
 ↓ placental passage
 ABO incompitability 
destruction of fetal RBCs
Not all isoimmunization  hydrops
2% of all women are isoimmunized
6 months postpartum
% of isoimmunisation with Rh-ve
ABO compatible fetus:
2% at delivery
7% 6 months postpartum
7% next pregnancy
Total = 16%
ABO blood group incompatibility:
- The most common cause of hemolytic
disease of the neonate
- 20% of all fetuses are ABO incompatible
only 5% of them are clinically affected
-  Mild anemia & ↑ reticulocytes
- No erythtoplastosis
- Treated by phototherapy
Difference from Rh incompatibility:
 Affect 1st baby
 Milder ( Ig M does not pass placenta)
 Rarely progressive
 Affect African Americans
Criteria of ABO incompatibility:
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1st day jaundice
Mother O, fetus A,B,or AB group
Anemia, ↑ reticulocytes
Management of ABO incompatibility:
Same as Rh isoimmunization but:
 No amniocentasis
 No blood transfusion
Because there is no hydrops
CDE blood group:
5 types: c, C, e, E, D
- D is +ve if present and –ve if absent
- D isoimmunisation is the most common
isoimmunization
- D –ve pregnant women are sensitized if
their fetus is D +ve
- CDE genes are inherited independent on
other blood groups
- They are located on chromosome 1
Geographic distribution of D +ve
populations:
 Native Americans
and Chinese
95%
 African Americans
92%
 Caucasians
87%
 Basque
76%
Other blood groups: % = 1
- ¼  Lewis blood group  mild
jaundice starts weeks postpartum
- 74% D, C, c, E & e antigens
- Recently Rh isoimmunization is ↓
due to Anit D treatment
- Now Rh
= 40%
Other Ags = 60%
Kell antigen:
- Caucasian kell +ve = 91%
- Isoimmunisation occur by pregnancy
or blood transfusion
-  Much earlier and more severe
anemia which can not be predicted
by:
 Maternal titer
 AF bilirubin = mild/moderate
- May  fetal death inspite of:
Blood transfusion
Normal AF bilirubin
- Hemolysis ↓ due to:
↓ RBCs
↓ bilirubin
- If maternal anti-Kell Ab titer ≥ 1 : 8
 Cordiocentesis because AF bilirubin
is out of proportion to anemia
Other antigens:
Kid Ag:
Jk a –ve = 25%
Jk b –ve = 25%
Jk a - b +ve = 50%
Duffy Ag:
Fy a – b –ve in some blacks
C Ag:
Most common Ag after D
 Moderate to severe hemolysis
IMMUNE HYDROPS
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Immune hydrops
Hyperbilirubinemia
Mortality
Identification of
isoimmunization
Fetal Rh genotype
IMMUNE HYDROPS
RBCs hemolysis by isoimmunization
 Hyperplasia of BM
 Hyperplasia of extramedulary
sites:
Liver
Spleen
Liver:
Fatty degeneration
Deposition of hemosidrine
Large canaliculi with bile
Heart: HF
Lungs: Hge - immature
When fluid accumulate in subcutanous
tissues  hydrops fetalis
Definition:
Abnormal fluid in ≥ 2 sites:
Ascitis – oedema – pleural effusion
Placenta:
 Enlarged cotyledons
 Odemotus villi
 Boggy
Fetus:
 Dystocia due to:
 Hepatospleenomegaly
 Odema
PATHOPHYSIOLOGY
Heart:
HF  hypoxia  capillary leakage
Extramedulary hyperpleasia:
Hepatic parynchemal distruction
 portal HTN
 umbilical vein HTN
Liver disease:
 ↓ protein
 ↓ colloidal osmotic P
Study:
Cordiocentesis in hydrops:
 Hb = < 3.5 gm/dL
 Plasma protein = < 2 SD
 AF plasma protein ↑
The degree of anemia affect
the degree of ascitis and made
worse by ↓ plasma proteins
Capillary endothelial damage:
 Capillary leakage
 ↓ protein
Study:
↑ Umbilical vein pressure is due to
cardiac dysfunction and not
portal HTN
Sinusoidal FHR = impending death
Neonate:
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Pale
Edematous
Limp
↑ need for resuscitation
Dyspnea
Collapse
Hepatospleenomegaly
Petechiae
ecchymosis
HYPERBILIRUBINEMIA
Less affected fetuses are born
normal  jaundice within hours
If untreated  kernicterus = CNS
damage affecting basal ganglia
Mortality:
Reduced dramatically due to:
 D Ig
 Blood transfusion
 Induction of labor
IDENTIFICATION OF ISOIMMUNIZATION
Maternal serum Abs:
Unbound to RBCs  disappear
within 1 – 4 months
 Indirect Coombs T
Fetal serum Abs:
Bound to RBCs  hemolysis
 Direct Coombs test
Neonatal blood group:
Inaccurate because D-Ag may
be coated with D-Ab
If maternal Abs are present:
 Ig G or Ig M ?
(Ig M can not pass the placenta)
If Ig G  antibody titer:
< critical value 1 : 16  repeat
> critical value 1 : 16  evaluate
Critical values for other Ags:
Kell ≥ 1 : 8
C, E ≥ 1 : 32
The presence of Abs in the
mother does not mean that:
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The fetus is +ve
He will be affected
Amnestic response:
= ↑ Ab titer + Rh –ve fetus
Because ½ of adult males are
heterozygous for D Ag 
¼ of women at risk are Rh -ve
Estimation of fetal genotype:
The father is tested for:
 Blood group
 Most likely arrangement of his CDE
genes = presumed genotype based
on the most common arrangement
of genes in men of his race
If the father is white:
 94% chance to be heterozygous
 47% chance of having D –ve fetus
MANAGEMENT
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Amniotic fluid evaluation
Expanded Liley graph
Fetal blood sampling
Subsequent child development
Other methods to ↓ hemolysis
Delivery
Exchange transfusion
Prevention
Routine antepartum anti-D
AMNIOTIC FLUID EVALUATION
↑ Hemolysis ↑ AF bilirubin
↑ anemia
Since AF bilirubin is very small 
measured by a continuously recording
spectrophotometer and is demonstrable
as a change in absorbance at 450 nm
( ∆ OD 450 ) then the results are
plotted on Liley graph (1961)
LILEY GRAPH
Zones of Liley graph:
Zone 1 = mild anemia
= 14 gm %
Zone 2 = moderate/severe anemia
= 13.9 – 8 gm %
Zone 3 = severe anemia
= < 8 gm %
= death in 7 – 10 days
If the results are in zone 1 or 2:
repeat in 1 – 2 weeks and draw
a line between the 2 results:
- If the trend of the line is:
 Decreasing
 Parallel to the lines of the graph
= unaffected fetus or stable
 repeat / 2 – 3 weeks until
transfusion or delivery
- If the trend of the line is:
- Rising within the zone
- Rising to zone 3
= Unstable
 Managed as zone 3
If the results are in zone 3:
= Severe anemia
 Immediate blood
transfusion or delivery
Expanded Liley graph:
Since Liley graph was made for fetuses
> 27 week, expanded graph back to
18 – 20 weeks is inaccurate, because
AF bilirubin < 25 weeks is high
So, in cases of:
 Hydrops
< 25 weeks
 Severe anemia < 25 weeks
It’s better to do cordocentesis
FETAL BLOOD SAMPLING
Cordocentesis is risky # amniocentesis
Advantages: blood typing
Recently  amniocytes for Rh typing:
 100% accurate
 99.7% sensitivity
 94% specificity
 Also for C,E , Kell & other Ags
If fetus is Rh–ve  no further tests
If amniocentesis  possible anemia
U/S
 hepatomegaly
NST/BPP
 fetal stress
 immediate blood
transfusion or delivery
Tests of cordocentesis:
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Hb%
HTV
Indirect Coombs titer
Reticulocyte count
Indications of IU blood transfusion:
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Hb 2 gm/dL < mean of normal
Hb in the fetuses in the same GA
HTV 30% = 2 SD < mean at all GAs
Methods of intrauterine blood transfusion:
Intraperitoneal - intraumbilical
Subsequent child development:
90% normal – delayed - abnormal
Other methods to ↓ hemolysis:
 Plasmapheresis
 Large dose of promethazine
 Corticosteroids for immunosuppresion
 D +ve erythrocyte membrane capsules
All are ineffective
DELIVERY
Aim:
= Delivery at or near term
Monitor by fetal wellbeing tests
If the fetus is very immature:
 Intrauterine blood transfusion
If near term:  deliver
 If lungs are mature  induce labor
 If compromised fetus  CS
EXCHANGE TRANSFUSION IN THE
NEWBORN
If the mother is sensitized
cord blood sample for:
 Hb%
 Direct Coombs test
If overtly anemic  exchange blood
transfusion by O –ve fresh blood
If not overtly anemic  the need for
blood transfusion is determined by:
 The rate of bilirubin ↑
 Maturity
 Complications
PREVENTION
By anti D Ig = 7S Ig G = 300 μg D Ab
Given within 72 hours of delivery
To none sensitized mothers only
Given after: abortion, mole, ectopic,
miscarrage
Rate of sensitization without D Ig:
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2% of spontaneous abortion
5% of elective abortion
6% of amniocentesis
ROUTINE ANTEPARTUM
ADMINISTRATION
At 28 weeks
For all Rh –ve pregnant women
↓ isoimmunization from 1.8 % to 0.07%
In the past :
2nd injection 34 weeks
½ life of Ig :
= 24 hours  Reduce titer by time
 weak +ve indirect Coombs test
Now the 2nd injection is given if:
 Fetomaternal Hg occurs
 Amniocentesis > 3 weeks
from the 1st injection
The 2nd dose is against:
 15 mL of D +ve RBCs
 30 mL of fetal blood
Sometimes Ab cross the placenta
 Weakly +ve direct Coombs test
Recognized by:
 No anemia
 No hyperbilirubinemia
Risk of transmission of diseases:
 HIV  inactivated by the factory
 hepatitis  patients are excluded
from donation  very low risk
LARGE FETAL–TO - MATERNAL HG
Rarely 1 dose of Anti D Ig is insufficient
= Very rare occur 1 : 1250 deliveries
To avoid this all Rh –ve women should
be tested after delivery by Kleihaure Batke or rosette tests
Number of ampoules:
= fetal blood/15
Du antigen:
A variant of D antigen:
Du +ve & Du -ve
Less antigenic
Treated as Rh D –ve
Maternal to fetal Hg:
Very rarely an Rh –ve female fetus
is sensitized inutero by her mother
= Grandmother theory
No need for Anti D prophylaxis

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