HEMOLYTIC DISEASE OF THE NEWBORN:

Introduction

Hemolytic disorders are the disorders causing destruction of RBC.

It includes:

 Feto- maternal blood group incompatibilities –

 Rh incompatibility , ABO incompatibility
 Other rare causes : Immunisation against Kell antigen being common
 Increased red cell fragility – congenital spherocytosis, elliptocytosis.
 Deficient red cell enzyme – Glucose-6-phosphate dehydrogenase
 Hemoglobinopathies - α thalassemia
 Acquired haemolysis – Infection ( bacterial, viral), DIC

1. ERYTHROBLASTOSIS FETALIS

Erythroblastosis fetalis is a potentially life-threatening blood disorder in a fetus or newborn infant.

Erythroblastosis fetalis is hemolytic anemia in the fetus or neonate caused by transplacental
transmission of maternal antibodies to fetal RBCs. The disorder usually results from incompatibility
between maternal and fetal blood groups, often Rh0(D) antigens.

Incompatibilities of ABO blood types do not cause erythroblastosis fetalis.

RH INCOMPATIBILITY

Rh incompatibility is a condition that develops when a pregnant woman has Rh-negative blood and the
baby in her womb has Rh-positive blood.

CAUSES
 Maternal exposure ( through blood transfusion, fetomaternal hemorrhage, amniocentesis, or
abortion) to foreign antigens on fetal RBCs causes the production and transplacental passage of
specific maternal immunoglobulin G (IgG) antibodies directed against the fetal antigens, resulting in
immune destruction of fetal RBCs.

If the mother is Rh-negative, her immune system makes antibodiesantibodies against the Rh-positive
fetal blood cells. These anti-Rh antibodies may cross the placenta into the developing baby, where
they destroy the baby's circulating red blood cells.
When red blood cells are broken down, they make bilirubinbilirubin, which causes an infant to become
yellow (jaundiced). Firstborn infants are often not affected -- unless the mother has had previous
miscarriages or abortions, which could have sensitized her system -- as it takes time for the mother to
develop antibodies against the fetal blood. However, second children who are also Rh-positive may
be harmed.
 Rh incompatibilitySYMPTOMS

Symptoms in a newborn baby may include:

 Anemia
 Edema (swelling under the surface of the skin)
 Enlarged liver or spleen
 Hydrops (fluid throughout the body's tissues, including in the spaces containing the
lungs, heart, and abdominal organs)
 Newborn jaundiceNewborn jaundice appears within 24 hours of age and rapidly
increases inintensity
 Low muscle toneLow muscle tone (hypotonia)
 Developmental delay

EXAMS AND TESTS

Specific tests depend on the type of erythroblastosis, but may include:

 Complete blood count

 Bilirubin level
 Blood typing

Blood tests done on the newborn baby

 Biochemistry tests for jaundice

 Peripheral blood morphology shows increased reticulocytes. Erythroblasts (also known
as nucleated red blood cells) occur in moderate and severe disease.

 Positive direct Coombs test (might be negative after fetal interuterine blood transfusion)

Blood tests done on the mother

Positive indirect Coombs test.

FETAL MANAGEMENT

All pregnant women should have blood typing, Rh determination, and an antibody screening
performed on their first prenatal visit.

 If the mother is Rh- positive and her antibody screening is negative, it may be advisable to
repeat the antibody screening later in pregnancy, but this will have a low yield.
 If the mother is Rh- negative/ antibody screen negative and the father of the fetus is Rh-
negative , she should be retested at 28 and 35 weeks gestation. If the father is Rh- positive, she
should be retested at 18-20 weeks and monthly therafter.If the paternal phenotype is heterozygous for
Rh (O) amniocentesis is used to determine the fetal blood type by PCR.
 If the mother is Rh- negative / antibody screen positive, the antibody titer is repeated at 16-18
weeks, at 22 weeks, and every 2 weeks thereafter. Amniocentesis is usually done for antibody titers >
 1: 16 or at a level at which the local center has had a fetal demise. Irrespective of antibody titers, if
there is a prior history of a severely isoimmunised fetus, serial amniocentesis may be indicated
beginning at 16 to 18 weeks to measure the optical density at a wavelength of 450 nm ( bilirubin) to
assess the risk for fetal death from hydrops. If the fetus is < 24 weeks ( optical density is less
accurate) or if placental trauma is likely with amniocentesis, direct percutaneous fetal blood sampling
for blood type, direct Coombs test, hematocrit, CBC, and blood gases may be preferable. Doppler
assessment of fetal middle cerebral artery peak blood flow velocity is emerging as an accurate tool to
predict fetal anemia and may replace amniocentesis for evaluation of fetal anemia.
 Fetuses at high risk for death may be treated at early delivery
 ( usually 30 weeks), but this requires careful fetal monitoring , induction of pulmonary
maturity, and close cooperation between obstetrician and neonatologist. If the hydrops fetus is too
immature for early delivery to be considered, intrauterine transfusion (intravascular or intraperitoneal
routes) indicated. It is repeated whenever fetal haemoglobin levels fall below approximately 10 g/dl.
Following transfusion, serial USG are done to assess changes in the degree of hydrops and fetal well
– being.
NEONATAL MANAGEMENT
 Cord bilirubin level < 4 mg/dl and Hb: > 14g/dl – require no treatment or only phototherapy.
 Cord bilirubin level < 4 mg/dl and Hb: < 14g/dl - have anemia, increased nucleated red cells
and reticulocytes on blood smear. These infants may have thrombocytopenia and a very elevated
WBC count. They have an enlarged liver and spleen,and require early exchange transfusion and
phototherapy. Infants with isoimmune haemolytic anemia may develop an exaggerated physiologic
anemia at 12 weeks of age, requiring blood transfusion. Erythropoietin is currently being evaluated
for use in preventing this late anemia.
High – dose intravenous immune γ- globin therapy 500 to 1,000 mg/kg IV is used for
haemolytic disease. Immunoglobulin block FC receptors, thereby inhibiting hemolysis and reducing
formation of bilirubin. It may accelerate the catabolism of endogenous IgG antibodies, thus reducing
the levels of circulating pathogenic or immune autoantibodies.

Possible Complications

 - Hydrops fetalis (potentially deadly fluid buildup and swelling in the baby)
 - Kernicterus (brain damage due to high levels of bilirubin)
 - Neurological syndrome with mental deficiency, movement disorder, hearing loss,
speech disorder, and seizures

Prevention

Prevention involves giving the mother Rh0(D) immune globulin at 28 wk gestation and within 72 h of
pregnancy termination. The standard dose is 300 μg IM. These injections prevent the development of
antibodies against Rh-positive blood.

 Delivery should be as atraumatic as possible. Manual removal of the placenta should be

avoided because it may force fetal cells into maternal circulation.

2. ABO incompatibility
ABO incompatibility is a reaction of the immune system that occurs when the mother’s blood group
‘O’ and baby’s blood group ‘A’ or ‘B’ are mixed together.

Causes

The mother with blood group O has got naturally occurring anti- A and anti- B agglutins. These
antibodies are mainly IgM and do not cross placenta. If the fetus happens to be blood group A or B
corresponding to that of Father, the immune antibodies are formed in response to the entry antigen
bearing fetal red cells, into the maternal circulation. As these are mainly IgG, they can cross the
placenta into the fetal circulation and cause a variable amount of hemolysis due to antigen- antibody
reaction.

In ABO incompatibility, the first baby may be affected. As intrapartum ‘boosting’ of immune anti-A
and anti- B antibodies does not occur, the progressive severe affection in successive babies is
unlikely. The affection is less because antibodies have got other tissue binding sites apart from the
fetal red cells.

Symptoms

 Back pain
 Blood in urine
 Feeling of "impending doom"
 Fever
 Yellow skin (jaundicejaundice)

Exams and Tests

 BilirubinBilirubin level is high

 Complete blood countComplete blood count (CBC) shows damaged red blood cells,
may also show mild anemiaanemia
 Lab testing of patient's and donor's blood shows that they are not compatible

Treatment

 Drugs used to treat allergic reactions (antihistamines)

 Drugs used to treat swelling and allergies (steroids)
 Fluids given through a vein (intravenous)
 Medicines to raise blood pressure if it drops too low
 Phototherapy
 Exchange transfusion

Possible Complications

 Kidney failure
 Low blood pressure needing intensive care
 Death

Prevention

Careful testing of donor and patient blood types before transfusion or transplant can prevent this problem.

3. IMMUNISATION AGAINST KELL ANTIGEN

Other fetomaternal incompatibilities that can cause haemolytic disorders involve the Kell, Duffy, Kidd, MNSs,
Lutheran, Diego, Xg, P, Ee, and Cc antigen systems, as well as other antigens. The Lewis antigen is a
commonly found antigen, but this antigen does not cause haemolytic disease of the newborn. Most Lewis
antibodies are of the IgM class ( which do not cross placenta) and the Lewis antigen is poorly developed and
expressed on the fetal and / or neonatal erythrocytes.

4. GLUCOSE -6- PHOSPHATE DEHYDROGENASE DEFICIENCY

The deficiency of G-6-PD in the red blood cells. The deficiency of G-6-PD deficiency gene is inherited as X-
linked recessive. Hemolysis may occur spontaneously or following exposure to certain oxident drugs and
infections. The infant may receive the offending drug transplacentally, through breast milk or directly.
Wearing of clothes protected with moth balls ( naphthalene) may initiate hemolysis. Apart from hemolysis,
there is reduced glucuronidation of bilirubin due to defective G-6-PD activity in the hepatocytes.
Methemoglobin reduction and flouroscence are useful screening tests while G-6-PD tetrazolium cytochemical
method is diagnostic to quantify the defect. Sudden, dramatic and unexplained elevation of serum bilirubin in
a newborn baby is a characteristic manifestation of G-6-PD deficiency.

5. HEREDITARY SPHEROCYTOSIS

It is characterised by anemia, hyperbilirubinemia and mild spleenomegaly any time during neonatal period.
Laboratory data shows spherocytosis and increased fragility of erythrocytes. Other causes of
microspherocytosis and spleenomegaly in the newborn such as ABO incompatibility and infections should be
ruled out. The abnormality is transmitted as autosomal dominant trait.In-vitro abnormal autohemolysis of RBC
can be corrected by addition of glucose.. Spleenectomy is curative but should be delayed as long as possible
due to increased risk of recurrent pneumococcal infections during infancy.

6. HOMOZYGOUS ALPHA- THALASSEMIA

In this alpha chain production is deficient while excess gamma chains combine to form Bart’s haemoglobin. The
infant is born with severe anemia, gross hepatospleenomegaly and anasarca without evidences of Rh iso-
immunisation. The diagnosis is suspected by negative direct Coomb’s test and confirmed by identification of
Bart’s haemoglobin on electrophoresis. The outcome is generally fatal.

7.DRUGS

Some drugs may aggravate neonatal jaundice by causing hemolysis ( vitamin K in large doses ), blocking Y-
acceptor protein ( vitamin k and kanamycin).They may predispose the baby to develop bilirubin brain damage
at lower serum bilirubin levels by blocking bilirubin sites in the albumin.
8. INFECTIOUS CAUSES

Intrauterine infections of TORCH complex can cause giant cell hepatitis and jaundice any time during neonatal
period.