This document discusses ABO incompatibility, which is a type of hemolytic disease caused by a reaction between maternal anti-A or anti-B antibodies and fetal A or B antigens. It is usually milder than Rh incompatibility. The severity of hemolysis is greater in OA incompatibility. Treatment may include phototherapy or exchange transfusion if bilirubin levels are too high.

1. g

2. ABO INCOMPATIBILITY
‫وترتیب‬ ‫تهیه‬
:
‫هللا‬ ‫داکترصفی‬
(
‫سلیمانخیل‬
)
‫رهنما‬ ‫استاد‬
:
‫امیری‬ ‫هللا‬ ‫نعمت‬ ‫دکتور‬ ‫استاد‬

3. Neonatal Hyperbilirubinemia
• Visible jaundice:
• Adults: >2mg%
• Newborns: >7mg
• Up to 50% of all newborns may develop
jaundice

4. Source of Bilirubin
• 75%: from old RBCs released from RES
• 25%: from ineffective erythropoyesis,
myoglobine, cytochromes, catalase,
peroxidase.
• Production of bilirubin:. 6-10 mg/kg/day.
(adults 3-4mg/kg/day)
• 1gr Hemoglobine produces 34mg of bilirubin

5. CO
Fe
ligandin
IB DB
UDPG-T

7. Best classified by age of onset and duration:
1. Early: within 24 hrs of life
2. Intermediate: 2 days to 2 weeks
3. Late: persists for >2 weeks
Causes of neonatal jaundice

8. Causes of neonatal jaundice
Early Intermediate Late/prolonged
• Haemolytic causes:
– Rh isoimmunisation
– ABO incompatibility
– G6PD deficiency
• Congenital infection
• Physiological jaundice
• Breast feeding jaundice
(inadequate intake)
• Sepsis
• Crigler-Najjar syndrome
(glucuronyl transferase
absent/reduced)
• Polycythaemia, bruising
• Conjugated (dark urine, pale
stools):
– Bile duct obstruction
– Biliary atresia
– Neonatal hepatitis
• Unconjugated:
– Breast milk jaundice
– Infection
– Hypothyroidism

9. Physiological jaundice
Characteristics
• Appears after 24 hours of birth.
• Maximum intensity by 4th-5th day in term & 7th day in
preterm.
• Serum level billirubine less than 15 mg/dl.
• Clinically not detectable after 14 days.
• Disappears without any treatment
Note: Baby should, however, be watched for worsening
jaundice.

10. Why does physiological jaundice
develop?
• Increased bilirubin load.
• Defective uptake from plasma
• Defective conjugation.
• Decreased excretion.
• Increased entero-hepatic circulation.

11. Pathological jaundice
• Appears within 24 hours of age.
• Increase of bilirubin > 5 mg/dl/day.
• Serum bilirubin > 15 mg/dl.
• Jaundice persisting after 14 days.
• Stool clay/white colored and urine staining clothes
yellow.
• Direct bilirubin > 2 mg/dl.

12. Risk factors for jaundice
JAUNDICE
• J - jaundice within first 24 hrs of life
• A - a sibling who was jaundiced as neonate
• U - unrecognized hemolysis
• N – non-optimal sucking/nursing
• D - deficiency of G6PD
• I - infection
• C – cephalhematoma /bruising
• E - East Asian/North Indian

13. Hemolytic disease of the
newborn
It is an isoimmunity hemolysis associated
with ABO or Rh incompatibility.
It results from transplacental passage of
maternal antiboddy active against RBC
antigens of the infant, leading to an
increased rate of RBC destruction.
It is an important cause of anemia and
jaundice in newborn infant.

14. ABO hemolytic disease
ABO incompatibility
Type O mothers
Type A or B fetuses
Presence of IgG anti-A or Anti-B antibodies in
type O mother
Frequently occurring during the first pregnancy
without prior sensitization
ABO incompatibility: 15% of pregnancies in US.
3% will develop significant jaundice.

15. ABO Incompatibility
This is a hemolytic disease caused by a
reaction of maternal anti-A or anti-B
antibodies with fetal A or B antigens
 Usually milder than Rh
except : sibling ABO , IgG anti A,B >1:64
 The severity of hemolysis more in OA
 The Antibody may produced to A&B antigen
Contained in food , bacteria and vaccine

16. ABO Incompatibility
• Relatively more common in female babies
• Relatively milder in preterm
• Direct coomb’s test is generally negative
or weak positive

17. Pathogenesis

18. Pathophysiology
Red blood cell breakdown
Hyperbilirubinemia
Jaundice
Kernicterus
Seizures etc.
Anemia
1. Liver
2. Spleen
3. Heart
4. Hydrops

19. Rh hemolytic disease
Rh blood group antigens (C, c, D, d, E, e)
D>E>C>c>e
Pathophysiology of alloimmune hemolysis
resulting from Rh incompatibility
An Rh-negative mother
An Rh-positive fetus
Leakage of fetal RBC into maternal circulation
Maternal sensitization to D antigen on fetal RBC

20. Production and transplacental passage
of maternal anti-D antibodies into fetal
circulation
Attachment of maternal antibodies to
Rh-positive fetal RBC
Destruction of antibody-coated fetal
RBC

21. Rh hemolytic disease was rare during the first
pregnancy involving an Rh-positive fetus.
Once sensitization has occurred, re-exposure
to Rh D RBC in subsequent pregnancies leads
to an anamnestic response, with an increase
in the maternal anti-Rh D antibody titer.
The likelihood of an infant being affected
increased significantly with each subsequent
pregnancy.

22. Significant hemolysis occurring in the
first pregnancy indicates prior maternal
exposure to Rh-positive RBC.
Fetal bleeding associated with a previous
spontaneous or therapeutic abortion
Ectopic pregnancy
A variety of different prenatal procedures
Transfusion of some other blood product
containing Rh D RBC in an Rh-negative
mother

23. Drugs That Cause Significant
Displacement of Bilirubin from
Albumin
Fusidic acid
Radiographic contrast
Aspirin
sulphonamides
Tolbutamide
Rapid infusions of albumin
furoseide
Rapid infusions of ampicillin
Indomethacin
ALB
drugs

24. • Early Phase :
– Hypotonia , high-pitched cry, Poor suck, and
lethargy
• Intermediate phase: Hypertonia of extensor
muscles (with opisthotonus, oculogyric crisis
rigidity and retrocollis), seizures.
• Advanced phase : seizures, hypotonia
replaces hypertonia , opisthotonus Pronounced
coma, and death
Acute bilirubin encephalopathy

25. Chronic bilirubin encephalopathy
(Kernicterus)
• Choreoathetoid
• cerebral palsy
• Upward gaze palsy
• Sensor neural
• hearing loss
• intellectual deficits

26. Kernicterus:
* Bilirubin deposits typically in basal ganglia, hippocampus, substantia nigra, etc.

27. Mechanism of neurotoxicity in
kernicterus
• Unbound (unconjugated) bilirubin is:
• neurotoxic at high levels
• lipophilic and can cross the blood-brain-barrier
Long term clinical sequelae
Bilirubin staining of affected areas
Dysfunction and death of neurons
Impairs mitochondrial functions
neurotransmitter synthesis
Binds to cell components
Bilirubin accumulates at nerve terminals

28. Clinical Manifestations
 Jaundice
 Anemia
 Hydrops
 Massive enlargement of the liver and
spleen
 Bilirubin encephalopathy (Kernicterus)

29. Hyperbilirubinemia & Clinical
Outcomes:
Deposits in
skin and
mucous
membranes
Unconjugate
d bilirubin
deposits in
the brain
Permanent
neuronal
damage
JAUNDICE
ACUTE BILIRUBIN
ENCEPHALOPATHY
KERNICTERUS

30. Clinical Manifestations
Clinical Features Of Hemolytic Disease
Clinical Features Rh ABO
Frequency Unusual Common
Anemia Marked Minimal
Jaundice Marked Minimal to moderate
Hydrops Common Rare
Hepatosplenomegaly Marked Minimal
Kernicterus Common Rare

31. Laboratory Diagnosis
Laboratory Features Of Hemolytic Disease
Laboratory Features Rh ABO
blood type of Mother Rh negative O
blood type of Infant Rh positive A or B
Anemia Marked Minimal
Direct Commb’s test Positive Negative
Indirect Commb’s test Positive Usually positive
Hyperbilirubinemia marked Variable
RBC morphology Nucleated RBC Spherocytes

32. Diagnosis
 Antenatal Diagnosis
History
Expectant parents’ blood types
Maternal titer of IgG antibodies to D or E
(>1:32)
At 12～16 wk
At 28～32 wk
At 36 wk
Fetal Rh and ABO status
Fetal jaundice level

33. Diagnosis
 Postnatal diagnosis
Jaundice at < 24 hr
Anemia (Hematocrit and hemoglobin
examination)
Rh or ABO incompatibility
Coomb’s test positive
Examination for RBC antibodies in the
mother’s serum

34. Treatment
 Main goals
To prevent intrauterine or extrauterine
death of fetal or infant form severe anemia
and hypoxic
To avoid neurotoxicity from
hyperbilirubinemia

35. Treatment
 Treatment of the unborn infant
Utero transfusion
Indication
Hydrops
Anemia (Hematocrit<30%)
Method
Packed RBC matching with the mother’s
serum
Umbilical vein transfusion

36. Treatment
Delivery in advance
Indication
Pulmonary maturity
Fetal distress
Maternal titer of Rh antibodies > 1:32
35～37 wk of gestation

37. Treatment
 Treatment of the liveborn infant
Immediate resuscitation and supportive
therapy
Temperature stabilization
Correction of acidosis: 1-2mEq/kg of sodium
bicarbonate
A small transfusion compatible packed RBC
Volume expansion for hypotension
Provision of assisted ventilation for respiratory
failure

38. • Depends on the cause and level and type of
bilirubin
• Unconjugated hyperbilirubinaemia:
• Ensure adequate fluid intake
• Phototherapy
• IV immunoglobulin
• Exchange transfusion
• Conjugated hyperbilirubinaemia:
• Ensure adequate nutrition
• Treat underlying problem
Treatment of Neonatal Jaundice

39. Treatment
Phototherapy
Blue spectrum of 425-475 nm (or White
or Green)
Irradiance:15μW/cm2/nm
Distance : 15-20 cm
Protection of eyes and genital
Three photochemical reactions:
1). photo isomerization
2). Structural isomerization
3). Photo-oxidation

40. Phototherapy
Biliblanket

41. Phototherapy
Spectrum of light
Blue is most effective (460 - 490 nm)
Ultraviolet light
(10 – 400 nm)
Infrared light
(600 – 700 nm)
Phototherapy is NOT:
• Ultraviolet light
• Infrared light
Bilirubin absorbance and transmittance
Maisels MJ et al. N Engl J Med 2008;358:920-8
Bilirubin absorbance

42. Phototherapy: Technique
• Fluorescents ,spots or biliblankets
• Naked , covering eyes
• Increase fluids 20-40 ml/kg/24h
• Check bilirubin every 12-24hs
• Stop: 13±0.7mg% in term, 10.7±1.2mg% in preterm
• Check 12-24hs later for rebound
• Phototherapy In ABO-HDN : if exceeds 10 mg/dL at 12
hours, 12 mg/dL at 18 hours, 14 mg/dL at 24 hours, or 15
mg/dL at any time. If the bilirubin reaches 20 mg/dL, an
exchange transfusion is done.

43. Phototherapy: Side effects
• Increased water loss
• Diarrhea
• Retinal damage
• Bronze baby, tanning
• Mutations in DNA?  shield scrotum
• Disturb of mother-infant interaction.

44. Premature infants
• 1. Infants <1,000 g. Phototherapy : within 24
hoursexchange transfusion :10 to 12 mg/dL.
• 2. Infants 1,000 to 1,500 g. Phototherapy : 7 to
9 mg/dL exchange transfusion : 12 to 15 mg/dL.
• 3. Infants 1,500 to 2,000 g. Phototherapy : 10 to
12 mg/dL and exchange transfusion : 15 to 18
mg/dL.
• 4. Infants 2,000 to 2,500 g. Phototherapy :13 to
15 mg/dL and exchange transfusion :18 to 20
mg/dL.

45. Copyright ©2004 American Academy of Pediatrics
Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316
Guidelines for phototherapy in hospitalized infants of 35 or more weeks' gestation

46. Exchange transfusion
Indication
 Cord Hemoglobin <11g/dl
 Cord bilirubin > 4.5mg/dl
 Hydrops, hepatosplenomegaly and heart failure
 Bilirubin in the 1st 12 of life>0.75mg/dl/hr
 Bilirubin concentration>20mg/dl
 The bilirubin level is rising >1 mg/dL/hour despite
phototherapy.
 Factors supporting early exchange transfusion:
Previous kernicterus in a sibling, reticulocyte counts
greater than 15%, asphyxia of neonate and
premature infant

47. Exchange transfusion
Blood volume of exchange transfusion
Double-volume exchange transfusion :160ml/kg
Blood choose of Rh incompatibility
Rh in accordance with mother
ABO in accordance with neonate
Blood choose of ABO incompatibility
Plasm of AB type
RBC of O type

48. Exchange transfusion
Aims of transfusions:
a. Remove antibodies
b. Remove bilirubin
c. Correct anemia
Potential complications:
a. Infection
b. Necrotizing enterocolitis NEC
c. Thromboembolic complications

49. Copyright ©2004 American Academy of Pediatrics
Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316
Guidelines for exchange transfusion in infants 35 or more weeks' gestation

50. treatment of hyperbilirubinemia in healthy term
babies
Age (hr) phototherapy exchange transfusion
Birth > 6 > 16
12 > 11 > 17
24-48 > 15 > 20
49-72 >18 >24
>72 >20 >25
#Phototherapy should result in a decline 1-2 mg/dL of total
bilirubin within 4-6 hour, should continue to fall and remain
below exchange transfusion levels.
*Intensive phototherapy, prepare for exchange, exchange if
bilirubin does not fall below exchange transfusion levels.

51. Exchange Transfusion
 With a exchange transfusion, approximately
87% of blood voiume will be replaced
 Serum bilirubin levels should decrease by
50%

52. Prevention
 Intramuscular injection of 300ug of human
anti-D globulin to an Rh-negative mother
Within 72 hr of delivery
Abdominal trauma in pregnancy
Amniocentesis
Chorionic villus biopsy
Abortion

53. Preventive and supportive
treatment
phenobarbitone : 10mg/kg IM single dose
OR 5mg/kg/day BID for 3days
 clofibrate 50 mg/kg single oral dose
 Adequate feeding
 treatment of sepsis
 IVIG : in Rh and ABO-HDN 0.5-1g/kg over
2hr

54. Drugs blocking enterohepatic
circulation
 Agar : sea-weed , orally 250mg every 6hr
 Cholestyramin : 1.5g/kg/d QID mixed in
milk
 Zinc gluconate : 10mg/kg/d q12hr

55. Miscellaneous drugs
 Orotic acid : precursor of UDPG-T its use
limited and cost is prohibitive
 Tin-mesoporphyrin: is a structural analog of
heme . It blocks the site on heme oxygenase
6 micromoles/kg IM single dose . Can also be used for
Crigler-Najar syndrome
 Albumin : 1g/kg (5%) 1hr before exchange

57. REFRENCES
 Care of the New Born MEHARBAN
SINGH
 Manual of Neonatal Care, 6th Edition
Cloherty, John P.; Eichenwald, Eric C.;
Stark, Ann R.
 Nelson Text book of Pediatric 20th
Edition