HinDifuN na GAME:

Immunoglobugame
 CONTENTS
01- 04- 07-
02- 05- 08-
06-
03- 09-
 C SE:
Maria Juana was admitted due to labor pains. She eventually
delivered a healthy 7-pound baby boy at 39 weeks. At 24 hours
after delivery, the baby was noted to be jaundiced; hence the
request to do blood typing on both the mother and the baby
and Coomb’s test on the baby.
 PAST MEDICAL
HISTORY:
The mother is G1P1 (1001), with
the baby as the very first child.
All pre-natal check-ups were
unremarkable. No history of
prior illness or hospitalization
in the mother.
PERSONAL
HISTORY
There are no records of
substance abuse, alcoholism
or tobacco smoking in the
mother.
FAMILY
HISTORY
There were no histories of
malignancies in the family.
There were likewise no
histories of Jaundice.
Hypertension and diabetes
were noted on his mother’s
side.
PHYSICAL
Examination
The mother’s vital signs were
normal on admission.
Baby was delivered cephalic
full-term with APGAR score of
9, with good cry. No cord coil
noted, no amniotic fluid
staining observed.
Complete Blood Count (Mother) Complete Blood Count (Baby)
WBC Count 11.0 x 109/L 16.0 x
WBC Count
109/L
RBC Count 4.5 x 1012/L
RBC Count 3.2 x 1012/L
Hemoglobin 130 g/L
Hematocrit 0.43 L/L Hemoglobin 9 g/dL
MCV 90 fL Hematocrit 0.26 L/L
MCH 32 pg MCV 81 fL
MCHC 34% MCH 28 pg
Platelet Count 350 x 109/L MCHC 34%
Differential Count Platelet Count 650 x 109/L
Segmented Neutrophil 48% Differential Count
Bands 12% Segmented Neutrophil 28%
Lymphocyte 30% Bands 12%
Monocyte 8% Lymphocyte 48%
Eosinophil 2% Monocyte 10%
Eosinophil 2%
 Forward Typing Reverse Typing Rh Typing
Anti - A Anti-B A Cells B Cell Anti-D D Control DAT
3+ 0 NT NT 1+ 0 2+

Forward Typing Reverse Typing Rh Typing

Anti - A Anti-B A Cells B Cell Anti-D D Control DAT
0 0 3+ 3+ 4+ 0 NT
* NT – Not tested

Reference Range
Bilirubin, Total 11 0.2 - 1.2 mg/dL
Bilirubin, Direct 1 0.1 - 0.4 mg/dL
 – Condition in which an infant’s skin appears yellow within the first few days
of life. The yellowish appearance is a sign of an increased blood pigment called Bilirubin, which
then settles in the skin.

- the woman has had one pregnancy and has delivered once

also called unconjugated bilirubin; is bound to a

certain protein (albumin) in the blood

– also called conjugated bilirubin; Water-soluble and ready

to be excreted into bile

- Blood test used to diagnose a type of anemia caused by your immune system

- Type of immunity that produces an immune response against

antigens from members of the same species

- Refers to the entry of fetal

blood into the maternal circulation before or during delivery.
 Patient assessment

PATIENT’S HISTORY:
Hypertension and diabetes were noticed on his mother’s side.

CHIEF COMPLAINTS:
In 24 hours after the delivery, the baby was noted to be jaundiced.

Sign and Symptoms:

Jaundice
 Laboratory results interpretation

Complete Blood Count (Mother) REFERENCE RANGE INTERPRETATION

WBC Count 11.0 x 109/L 5.0-10.0X109/L Above Normal
RBC Count 4.5 x 1012/L 3.80-5.20 1012/L Normal
Hemoglobin 130 g/L 120-150 g/L Normal
Hematocrit 0.43 L/L 0.35-0.49 L/L Normal
MCV 90 fL 80-100 fL Normal
MCH 32 pg 26-34 pg Normal
MCHC 34% 32-36 Normal
Platelet Count 350 x 109/L 150-450 x 109/L Normal

Differential Count (Mother) REFERENCE RANGE INTERPRETATION

Segmented Neutrophil 48% 50-70% Normal

Bands 12% 2-6 % Above Normal
Lymphocyte 30% 18-42% Normal
Monocyte 8% 2-11 % Normal
Eosinophil 2% 1-3 % Normal
 Laboratory results interpretation
Complete Blood Count (Baby) REFERENCE RANGE INTERPRETATION
WBC Count 16.0 x 109/L 9.0-37.0 X109/L Normal
RBC Count 3.2 x 1012/L 4.10-6.10 x 1012/L Below Normal
Hemoglobin 9 g/dL 16.5-21.5 g/dL Below Normal
Hematocrit 0.26 L/L 0.48-0.68 L/L Below Normal
MCV 81 fL 95-125 fL Below Normal
MCH 28 pg 30-42 pg Below Normal
MCHC 34% 30-34 Normal
Platelet Count 650 x 109/L 150-450 x 109/L Above Normal

Differential Count (Baby) REFERENCE RANGE INTERPRETATION

Segmented 32-67% Below Normal
28%
Neutrophil
Bands 12% 0-8% Above Normal
Lymphocyte 48% 25-37% Above Normal
Monocyte 10% 0-9% Above Normal
Eosinophil 2% 0-2% Normal

Chemistry (Baby) Reference Range INTERPRETATION

Bilirubin, Total 11 0.2 - 1.2 mg/dL ABOVE NORMAL
Bilirubin, Direct 1 0.1 - 0.4 mg/dL ABOVE NORMAL
Laboratory results interpretation
Blood Grouping of the Mother
Forward Typing Reverse Typing Rh Typing DAT
Anti - A Anti-B A Cells B Cell Anti-D D Control
0 0 3+ 3+ 4+ 0 NT

INTERPRETATION: The Mother’s Blood type is: O- Rh Positive (+)

Blood Grouping of the Baby

Forward Typing Reverse Typing Rh Typing DAT

Anti - A Anti-B A Cells B Cell Anti-D D Control

3+ 0 NT NT 1+ 0 2+

INTERPRETATION: The Baby’s Blood type is: A - Rh positive (+)

DAT Test: POSITIVE (+) Medium sized agglutinates- clear background
 Parameters HDN caused by HDN caused by Hereditary G6PD deficiency Sepsis Alpha-
ABO Rh spherocytosis Thalassemia
incompatibility incompatibility
Jaundice (1-4 days) (2-3 days)
Anemia (rare)
First pregnancy is (rare) (No increased (No increased (No increased (No increased
affected
severity) severity) severity) severity/risk)
Low Hemoglobin

Low Hematocrit

Low MCV X (variable) x x (normal)

Low MCH

Lymphocytosis

Neutropenia x x
Monocytosis x
Thrombocytosis x x x
Neonatal (peak at 1-3 days)
hyperbilirubinemi
a
DAT + x x x
ABO x x x
Incompatibility
 HEMOLYTIC DISEASE OF THE NEWBORN:

Neonatal jaundice
: abo incompatibility
Jaundice is the medical term
for a yellowish tinge of the
skin.

The yellow color is caused

by a substance called
bilirubin, which is made
normally in the body. Babies
with higher than normal
blood levels of bilirubin, a
condition called
"hyperbilirubinemia," get
this yellow color when
bilirubin builds up in the
skin.
Hemolytic Disease of the Newborn (HDN), also known as
erythroblastosis fetalis, isoimmunization, or blood group
incompatibility, occurs when fetal red blood cells (RBCs), which
possess an antigen that the mother lacks, cross the placenta
into the maternal circulation, where they stimulate antibody
production. The antibodies return to the fetal circulation and
result in RBC destruction.

▪ The average life span of red cells in full term neonates is 60

to 90 days,
▪ used to be a major cause of fetal loss and death among
newborn babies.
▪ Rate of RBCs destruction is accelerated but ability of bone
marrow to respond is NORMAL
▪ Also called HYDROPS FETALIS as severely affected fetuses
may develop generalized edema
 IMMUNE-MEDIATED HEMOLYTIC DISEASE

(Alloimmune Hemolytic Disease of the Newborn)

Alloimmune HDN is due to the action of transplacentally transmitted maternal IgG antibodies on
paternally inherited antigens present on fetal red cells, but absent on the maternal red cells.

Alloimmune
HDN

Hemolytic disease
Rh incompatibility due other to Red
cell antigens

ABO incompatibility
 Risk to develop HDFN in antigen-positive children and clinical
Antibody specificities
course of disease

ABO Low risk for disease, in general mild, incidentally severe

High risk for disease, often (very) severe, otherwise mild

Rh
High risk for disease, (very) severe or mild
D
Medium risk for disease, sometimes severe, but mostly
c
mild
E
Medium risk for disease, incidentally severe, but mostly
Other Rh antigens
mild
Kell
High risk for disease, (very) severe or mild
K
Medium risk mild to severe disease
Other Kell antigens

Duffy
Medium risk for disease, mostly mild
Fya/Fyb

Kidd
Low risk for disease, only mild
Jka/Jkb

Low risk for disease, mostly mild disease, very rarely

MNS
severe
M, N, S, s
Low risk for disease, mostly mild disease, very rarely
Other antigens
severe

No risk, because of very low expression of these antigens

I, Le, P1, Lu, Yt
by fetal cells

Other antigen systems Very low risk, very rarely severe disease can develop
Minor blood group INCOMPATIBILITY
In contrast to Rh and ABO sensitization, HDN attributable to Kell
sensitization is caused by anti-K suppressing the fetal production of
RBCs. Unlike Rh and ABO, Kell antigens are expressed on the surface of
RBC precursors, and anti-K promotes the immune destruction of K+
erythroid early progenitor cells by macrophages in the fetal liver (rather
than only mature fetal RBCs). Because the RBC precursors do not contain
hemoglobin, less bilirubin is released during the hemolysis, and jaundice
in the newborn period is less common. However, the underlying anemia
may be severe

Maternal-fetal incompatibilities within the Duffy blood group

Anti-Kidd antibodies are also a cause of hemolytic disease
of the newborn (HDN), the severity of the disease varies
but tends to be mild in nature. During pregnancy, fetal Kidd
antigens are capable of causing alloimmunization of the
mother . But in contrast to the hemolytic activity of Kidd
antibodies in incompatible blood transfusions, anti-Jka and
anti-Jkb are only rarely responsible for severe HDN .
Likewise, anti-Jk3 is a rare cause of HDN, but the first
documented case in Mrs. Kidd's newborn was fatal.
system is an uncommon cause of HDN. The disease tends to be mild
in nature. The Duffy antigens known to have caused maternal
immunization and subsequent hemolytic disease are Fya , Fyb and
Fy3 .
Of the MNS antibodies, anti-S is more common than anti-s, and
both are capable of causing severe hemolysis.
Less common causes of HD
 ABO INCOMPATIBILITIES

• 1 in 70 to 180 with an estimated of 1 in

150 births
HDFN is caused by the destruction of the fetal
•
RBCs by antibodies produced by the mother.
• Occurs most frequently in group O
mothers who have group A and group B
In the case of HDFN, the antibodies are
infants.
directed against the blood group antigens on
•
the fetal RBCs that were inherited from the
• Can occur in the first pregnancy and in
father.
any, but not necessarily all.
HDFN is caused by:
• ABO incompatibilities
NON-ABO HDFN
• RH incompatibilities
• Other minor blood group antigens (kell
• Approximately 93% of cases of non-ABO
and kidd)
HDFN is accounted to Anti-D
• Thalassemia
• Autoimmune hemolytic anemia
• Anti-D occurred alone or in combination
with another Rh antibody such as anti-C.

The incidence of Rh-negative in the European
and American whites is about 15-17%; it is
very much insignificant in China (1%) and
almost nil in Japan.
About 60% of the Rh-positive mean are
heterozygous and 40% are homozygous at the
D locus.
Overall, a Rh-negative woman having the
chance of Rh-positive fetus is 60%,
irrespective of the father’s genotype (South
India – 5%, North India -10%) in hospital
statistics.
ABO incompatibility frequently occurs during the first
pregnancy and is present in approximately 12% of
pregnancies, with evidence of fetal sensitization in 3%
of live births. Less than 1% of births are associated
with significant hemolysis.
Risk factors for ABO incompatibility are present in 12–
15% of pregnancies, but evidence of fetal sensitization
(positive direct Coombs test) occurs in only 3–4%.
Symptomatic ABO hemolytic disease occurs in <1% of
all newborn infants but accounts for approximately
two-thirds of observed cases of hemolytic disease in
the newborn.
On 2017, Philippine General Hospital studied the
Etilogy of the Hydrops Fetalis because of its
significant morbidity and mortality. There are 72
patients from 2010-2011 with hydrops fetalis and the
majority cause is undetermined.
On the other hand, According to the 2019 Philippine
Health Statistics, one of the fetal deaths in 2019 is due
to Hydrops fetalis due to Hemolytic Disease and there
are 62 patients who died in this disease.
 • Amniocentesis- This test is done to check the amount of bilirubin in the amniotic
fluid:
• Introduction of a needle into the amniotic fluid sac for the purpose of
withdrawing fluid.
• Maternal antibody titer- It is routine to evaluate for maternal antibodies at the first
prenatal visit, and if initially negative, to retest at 28 weeks and then after delivery.
• Ultrasound- to detect organ enlargement or fluid buildup in the fetus.
• Amniocentesis - to measure the amount of bilirubin in the amniotic fluid
• Sampling of some of the blood from the fetal umbilical cord during pregnancy

Father Testing
• Investigative tests on the father depend on which maternal antibodies are present.
• Test for weak D if initial Rhesus typing appears to be D-negative.

Molecular Genotyping
In prenatal testing programs, molecular typing can determine the Rhesus type of the
mother, father, and fetus and may be done if the mother has anti-D or another antibody
known to cause hemolytic disease of the newborn.
Once a baby is born, diagnostic tests for hemolytic disease of the newborn may include the
following:

• Testing of the baby’s umbilical cord blood for blood group, Rhesus factor, red blood
cell count, and antibodies

• ABO blood group system (anti-A and anti-B), Rhesus system (Rhesus D, E, e, C and antibody
combinations (i.e., anti-Rhc and anti-RhE antibodies occurring together) - can be severe ,Kell
system (anti-Kell , anti-K 1 antibodies - common and also anti-K 2, anti-K 3 and anti-K 4
antibodies - rare and other blood group antibodies (Kidd, Lewis, Duffy, MN, P and others).

• Full blood count - the hemoglobin level and platelet count are important
• Peripheral blood morphology shows increased reticulocytes.
• Biochemistry tests for jaundice: Bilirubin (total and indirect)
• The Direct Antiglobulin Test (DAT) is an important tool for identification of Hemolytic
Disease of the Newborn (HDN) caused by erythrocyte immunization.
• The Acid elution technique of Kleihauer-Betke test or flow cytometry
on a postnatal maternal blood sample can confirm that fetal blood
has passed into the maternal circulation.

• The Indirect Coombs test is used to screen blood from antenatal

women for IgG antibodies that may pass through the placenta and
cause hemolytic disease of the newborn. It is used in the prevention
of HDN.

The indirect Coombs test finds anti-D antibodies in the mother's

serum. If these were to come into contact with fetal RBCs they would
hemolyze them and hence cause HDN. By finding maternal anti-D
before fetal RBCs have been attacked, treatment can be given to
prevent or limit the severity of HDN.
 – Check blood flow of the baby by a Doppler Ultrasound.
An Umbilical artery Doppler test uses reflected sound waves to see
how blood flows through a blood vessel. The sound waves bounce off
solid objects, including blood cells. The movement of blood cells
causes a change in the pitch of the reflected sound waves. This is
called the Doppler Effect.

is a procedure that provides

blood to a fetus, most commonly through the umbilical cord. It is
used in cases of severe fetal anemia.

- If the baby gets certain complications, he or she

may need to be born early. Your healthcare provider may induce labor
may once your baby has mature lungs.
• This may be done if your baby has severe anemia.

• This may be done if your baby has low blood pressure.

• This test removes your baby’s blood that has a high bilirubin
level. It replaces it with fresh blood that has a normal bilirubin
level.

• IVIG is thought to decrease hemolysis by blocking Fc receptor

sites of reticuloendothelial cells preventing lysis of neonatal
erythrocytes
 • The baby is put under a special light. This helps your
baby get rid of extra bilirubin. It lowers the bilirubin
levels in your baby's blood through a process called
photo-oxidation.

Values at which one would consider starting phototherapy will be

different depending on which group your baby belongs to:
– Infants born at 38 weeks of gestational age or more and
without any additional risk factors for jaundice.
– Infants born at 38 weeks or more with risk factors for
jaundice
– Infants born between 35 weeks and 37 6/7 weeks
without any risk factors for jaundice
– Infants born between 35 weeks and 37 6/7 weeks with
additional risk factors for jaundice
The goal for phototherapy is to stop a rapid rise in bilirubin and
decrease bilirubin concentration if it is at dangerous levels. In most
cases, after a few days, a newborn baby’s body will be able to resolve
jaundice on its own. Frequently treatment is discontinued in stages; we
go from triple phototherapy to double and then to single
Risk factors that would place your baby in Groups 2 or 4
are:
✓ Isoimmune hemolytic disease (ABO or Rh conflict)
✓ G6PD condition (inadequate amount of glucose-6-
phosphate dehydrogenase) – can be diagnosed with
a blood test
✓ Asphyxia at birth – very low Apgar score at birth
✓ Significant lethargy
✓ Temperature instability
✓ Sepsis = overwhelming infection
✓ Acidosis – more acid in the blood than normal
✓ Low albumin level in the blood (if measured)
• Baby may need oxygen, or a mechanical breathing machine to
breathe better. There are several ways to deliver oxygen to a
baby.
➢ An oxygen hood or head box is used for babies who can
breathe on their own but still need extra oxygen.
➢ A thin, soft, plastic tube called a nasal cannula may be used
instead of a hood.
➢ Another method is a nasal CPAP system. CPAP stands for
continuous positive airway pressure.
➢ Finally, a breathing machine, or ventilator, may be needed to
deliver increased oxygen and breathe for the baby.
Another ultrasound technique called fetal middle cerebral artery peak systolic velocity (MCA-PSV) which cans
clinically diagnosed fetal Anemia at about 16 to 20 weeks of gestation

- The measurement is based on the reduced blood viscosity at lower hematocrits and resulting in faster
velocity of the blood.
- Readings are typically done every 2 weeks to track the degree of fetal anemia
Anti-D prophylaxis means giving special antibodies that recognize the D antigen to prevent your body from producing
your own antibodies against RhD positive blood cells (known as a ‘sensitization’) and in turn preventing the
development of HDFN.

Your blood group and RhD status are identified at
the beginning of your pregnancy from a blood group
sample taken with the routine ‘booking’ bloods.
RAADP is:
❑ given pregnant women who are RhD negative as
a single injection of 1500 international units of
Rhophylac 300
❑ administered intramuscularly in the upper arm.
❑ given between 28-30 weeks of pregnancy
If you are RhD negative, after you have given
birth, a blood sample is taken to test your
baby’s blood group and RhD status.
If your baby’s blood group is found to be RhD
positive, you will be offered a further injection
of anti-D.
This is known as postnatal anti-D prophylaxis.
RhoGAM is a medicine that stops your blood from making antibodies that attack Rh-positive blood cells.
RhoGAM is a sterilized solution made from human blood that contains a very small amount of Rh-positive proteins.

RhoGAM is given at 28 weeks of pregnancy to protect you for the rest of your pregnancy.
RhoGAM works for about 13 weeks.
Soon after you give birth, your baby’s blood will be tested for Rh.
If your baby has Rh-positive blood, you will get another dose of RhoGAM within 72 hours after you give birth.

If you have hemolytic anemia , or you have had an allergic reaction to a shot of immune globulin , or you already have
Rh sensitization, you should not get the RhoGAM shot .
 Mild anemia
Severe Hyperbilirubinemia and
Hyperbilirubinemia
Jaundice
Jaundice

Severe Anemia Bilirubin Encephalopathy

Hydrops Fetalis Kernicterus

Seizures
Brain damage
Deafness
 THANK YOU

FOR PLAYING!
REFERENCES:
• Abadingo, M.E., Alcausin, MML. B. (2017). Etiology of Hydrops Fetalis at the Philippine General Hospital:A Retrospective
Study. Retrieved on October 11, 2021, from https://actamedicaphilippina.upm.edu.ph/index.php/acta/article/view/538
• Albornoz, RA. M. et al. (2019). The 2019 Philippine Statistics. Retrieved on October 11, 2021, from
https://doh.gov.ph/sites/default/files/publications/2019PHS_Final_092121.pdf
• Bancalari E, Claure N, Jain D. Neonatal respiratory therapy. In: Gleason CA, Juul SE, eds. Avery's Diseases of the Newborn.
10th ed. Philadelphia, PA: Elsevier; 2018:chap 45.
• Branch DW, et al. (2008). Immunologic disorders in pregnancy. In RS Gibbs et al., eds., Danforth's Obstetrics and Gynecology,
10th ed., pp. 313–339. Philadelphia: Lippincott Williams and Wilkins
• California Association for Medical Laboratory Technology: Hemolytic Disease of the Newborn
• D.B. Gregory, G. A (2012) Gregory’s Pediatric Anesthesia (6th Edition)This edition first published 2020 © 2020 John Wiley &
Sons Ltd Keohane
• Dean, L. (1970, January 1). The MNS blood group. Blood Groups and Red Cell Antigens [Internet]. Retrieved October 12,
2021, from https://www.ncbi.nlm.nih.gov/books/NBK2274/.
• E.M. Smith, L. J. Walenga, J. M. Rodak's Hematology: Clinical Principles and Application (5th Edition)
• Esan AJ, J Hematol Blood Transfus Disord 2016, 3: 008 DOI: 10.24966/HBTD-2999/100008
• Harmening, D. (2019). Modern Blood Banking & Transfusion Practices (7th edition). Philadelphia: F. A. Davis Company
• Hinderliter SA, Gregory DS. Resuscitation of the newborn. In: Kellerman RD, Rakel DP, eds. Conn's Current Therapy 2021.
Philadelphia, PA: Elsevier 2021:1302-1308.
• Moise KJ (2009). Hemolytic disease of the fetus and newborn. In RK Creasy, R Resnik, eds., Creasy and Resnik's Maternal-
Fetal Medicine, 6th ed., pp. 477–503. Philadelphia: Saunders Elsevier.
• Turgeon, ML. (2014). Immunology & Serology in Laboratory Medicine (5th edition). St. Louis, Missouri: Elsevier mosby
Andropoulos,
• Vento M. Oxygen therapy in neonatal resuscitation. In: Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's
Neonatal-Perinatal Medicine. 11th ed. Philadelphia, PA: Elsevier; 2020:chap 33.