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Haemolytic Disease of the Newborn (HDN)

Definition Pathogenesis
Neonatal Anaemia, Hyperbilirubinemia caused by Incompatibility between
Maternal & Fetal RBC
↓ Lifespan of Fetal/ Neonatal RBC
Due to Maternal Alloantibodies against Red Cell Antigen inherited from Father
Maternal IgG cross placenta, bind to Fetal Red Cell with corresponding Antigen
Antibodies commonly cause HD N
Rh system
ABO system

Rh Haemolytic Disease of Newborn (Rh HDN)

Definition
Rh +ve 1st born infant is unaffected
Before delivery, risk of sensitization – 1.5-1.9%
Greatest risk at Delivery
Placenta separates, Fetal RBCs carrying Rh Antigen inherited from Father enter
Maternal circulation
Mother is Immunized and Anti-D is produced
HDN due to Anti-D is ↑ severe than due to other alloantibodies (Anti c, E)
All subsequent offspring inheriting D Antigen will be affected
Maternal Anti-D crosses placenta, binds to Fetal Rh +ve cells
Sensitized RBCs are destroyed by Fetal RES – Anaemia

Process of RBC Haemolysis goes on as long as Maternal’s Antibody persist in

Infant’s circulation
Rate of Haemolysis ↓ after birth
(No more maternal Antibody entering Infant’s circulation)
IgG is distributed Intravascularly & Extravascularly
Half life – 25 days
Haemolysis continues for several days → weeks (after delivery)

Diagnosis
Factors Affecting Immunization & Severity Serologic Testing
Antigenic Exposure Blood Grouping, Antibody screening at 1st booking
Transplacental Haemorrhage (7% of women during gestation) Preferably in 1st Trimester
Nucleated Fetal Cell in circulation in Pregnant Women (50-60%) ABO, Rh Testing
Trauma ↑ risk of Fetomaternal Haemorrhage Test ABO, Rh for D antigen
↑ Fetomaternal haemorrhage at Delivery Test should include weak D
≈ 1ml of Fetal RBCs can Immunize Mother (patient’s RBC simultaneously test with Rh control reagent)
Number of Antigenic sites on Fetal RBCs – (Dd)Heterozygous, (DD)Homozygous If weak D +ve, Patient is Rh +ve
Host Factors Weak D phenotype with missing part of Rh antigen
Ability to produce Antibody depends on Individial Complex Genetic Factors (may produce Antibody D)(cau se HDN)
(Responders, Nonresponders) Antibody Screening
Immunoglobulin Class IgG Alloantibody
Only IgG can Cross Placenta React at 37°C
IgG1, IgG3 are ↑ efficient in RBC Haemolysis If antibody screening is nonreactive
Active Transport of IgG begins in 2nd Trimester → Birth (repeat at 20-24 weeks gestation & at delivery)
Antibody Specificity Antibody Specificity
Rh D is Most Antigenic Anti I, Anti IH, Anti Le, Anti P – Cold IgM (can be ignored)
Immunogeni c – Anti D, c, E, e, C Anti M or Anti N – can be IgM or IgG or combination
Non Rh system Antibodies, Anti Kell most clinically significant Can cause HDN Mild → Moderate
Influence of ABO Group Rh –ve pregnant women
When mother is ABO incompatible with fetus (weak reactive antibody during 3rd trimester)
• Detectable Fetomaternal Haemorrhage ↓ (due to Rh Ig given after fetomaternal haemorrhage or at 28 weeks gestation)
• Incidence of Rh Immunization ↓ Titre > 4 – Active Immunization
Protection – Haemolysis of ABO Incompatible (Rh +ve) Fetal RBC in Mother’s Titre < 4 – Active Immunization cannot be ruled out but ↓ likely
circulation before it can be recognized by mother’s immune system Other than Antibody D, most common & significant – Anti K, E, c, C, Fya
Amniocentesis & Cordoce ntesis
Cause of HDN 18-20 weeks of gestation
Common Rare Never History of severely affected fetus & early fetal death
Anti D Anti fya Anti Lea Assess status of fetus
Anti D+C Anti s Anti Leb [Bilirubin] in amniotic fluid correlates with degree of Fetal Anaemia
Anti D+E Anti M Anti I
Anti C Anti N Anti IH
Anti E Anti S Anti P1
Anti c
Anti e
Anti K
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ABO Haemolytic Disease of Newborn (ABO HDN)

Fetal Management Definition

Intrauterine Transfusion Early Delivery 60% of HDN are caused by ABO Incompatibility
Indications Moderate → Severe Disease ABO incompatibility – most common cause of HDN
Very ↑ Bilirubin Interrupt transport of maternal
Cordocentesis Hb < 10g/dL antibodies to fetus Pathophysiol ogy
Fetal hydrops in Ultrasound Allow exchange transfusion Maternal ABO IgG – cross placenta &
attach to fetal ABO incompatible RBC
Serologic Testing for Newborn Infant ↓
ABO Groupi ng Rh Typing Direct Antigolulin Fetal RBC destruction,
Testing (DAT) lead to severe Anaemia (extremely rare)
ABO antigen not fully If DAT +ve, Red cell +ve ↓
developed in newborn heavily sensitized with (antibody coating Manifested by early onset of Jaundice
Does not have Antibody D infant’s RBC) (within 12-24h of birth)
Isoagglutinin
Reverse grouping Factors Affecting Incidence & Severity
cannot be used to Group O individuals - ↑ Titers of IgG antibodies
confirm ABO group Usually restricted to group O Mothers possessing Anti-A, Anti-B
Lack of severity due to
Management of Newborn Infant • Slow development of ABO Antigens on fetal red cell
Phototherapy Exchange Transfusion Newborn Transfusion • ABO Antigens are fully developed after 1st year of life
Mild → Moderate Severe Haemolysis Full term newborn • No. of ABO sites much smaller than in adults
Haemolysis (Hb <12 g/dL) • Widespread occurrence of A, B Antigen (red cell, plasma, other cells)
Require Packed Cell transfusion (Partially neutralised maternal antibodies)
(anaemia)
Exchange Transfusion Lab Investigations
Remove ↑ level of Mother – Presence of Ig G Anti-A, Anti-B with tier of > 64
Unconjugated Bilirubin, Infant – Group A or B
Maternal Antibodies, DAT +ve, weak +ve or –ve
Sensitized RBC, FBP
Replace Incompatible RBC with RBC Agglutination
compatible RBC Spherocytosis (not seen in Rh HDN)
Selection of Blood for Neonatal Transfusion Reticulocytosis
Group O RBC Polychromasis
CMV –ve ↑ Nucleated RBC
Gamma Irradiated (for Premature) Bilirubin peak – later at 1-3 days
Rh –ve units (for unknown blood group or Rh –ve)
For Exchange Transfusion, Whole blood ≤ 5days Treatment
Phototherapy Exchange Transfusion
Rh Immunoglobulin Severe Anaemia
Mechanism of Action (Antibody Mediated Immune Suppression)(AMIS) Using group O donor
Rh Ig attaches to fetal Rh +ve RBC in Maternal circulation (with ↓ Ɵter AnƟ-A, Anti-B)
↓
Antibody coated RBC are trapped in Spleen
↓
Activate Suppressor cell
↓
Suppresses 1° Immune Resp onse
Indications
Post partum Antenatal
Within 72h after delivery Rh Ig should be given in early 3rd
Mother – Rh –ve or weak D –ve Trimester or at 28 weeks gestation
Infant – D +ve or weak D +ve Newborn may have +ve DAT
Infant – unknown type (stillbirth), If infant is Rh +ve, 2nd dose is
Rh Ig should be given indicated after delivery
Tଵ/ଶ of Rh Ig = 25 days
Considerations
Im – Im only
Rh Ig is of no benefit once Mother has been actively immunized
(Formed Antibody D)
Rh Ig must not be given to newborn infant

ABO vs Rh HDN
Characteristic ABO Rh
1st Pregnancy Yes Rare
Disease predicted by titers No Yes
IgG Antibody Yes Yes
Bilirubin at Birth Normal ↑
Anaemia at Birth No Yes
Phototherapy Yes Yes
Exchange Transfusion Rare Common
Intrauterine Transfusion None Sometimes
Spherocytosis Yes Rare