Hemorrhogic Disease of the New-born

 Hemolytic Disease of the New born
 HDN because of ABO Incompatibility
 HDN because of Rh Incompatibility
5/16/2021 Yaregal S. CN. NN., Wollo University 1

ABO Incompatibility
 In ABO hemolytic disease of the newborn (also known
as ABO HDN), maternal IgG antibodies with specificity for
the ABO blood group system pass through the placenta to
the fetal circulation where they can cause hemolysis of
fetal red blood cells which can lead to
fetal anemia and HDN.

 ABO incompatibility is more common and less severe condition
 Risk factors
 In about a third of all ABO incompatible pregnancies maternal IgG
anti-A or IgG anti-B antibodies pass through the placenta to the
fetal circulation leading to a weakly positive direct Coombs test for
the neonate's blood.
 However, ABO HDN is generally mild and short-lived and only
occasionally severe because:

 IgG anti-A (or IgG anti-B) antibodies that enter the fetal
circulation from the mother find A (or B) antigens on many
different fetal cell types, leaving fewer antibodies available for
binding onto fetal red blood cells.
 Fetal RBC surface A and B antigens are not fully developed
during gestation and so there are a smaller number of
antigenic sites on fetal RBCs.

 Routine antenatal antibody screening blood tests (indirect
Coombs test) do not screen for ABO HDN.
 If IgG anti-A or IgG anti-B antibodies are found in the pregnant
woman's blood, they are not reported with the test results,
because they do not correlate well with ABO HDN.
 Diagnosis is usually made by investigation of a newborn baby
who has developed jaundice during the first week of life.

 Coombs - after birth baby will have a direct coombs test run to
confirm antibodies attached to the infant's red blood cells.
 This test is run from cord blood.
 In some cases, the direct coombs will be negative but severe,
even fatal HDN can occur; an indirect coombs needs to be run in
cases.
 Hgb - the infant's hemoglobin should be tested from cord blood.
 Reticulocyte count - Reticulocytes are elevated when the infant is
producing more blood to combat anemia.

 Neutrophils - as Neutropenia is one of the complications of HDN,
the neutrophil count should be checked.
 Thrombocytes - as thrombocytopenia is one of the complications
of HDN, the thrombocyte count should be checked.
 Bilirubin should be tested from cord blood.

 The antibodies in ABO HDN cause anemia due to destruction of
fetal red blood cells and jaundice due to the rise in blood levels
of bilirubin, a bi-product of hemoglobin break down.
 If the anemia is severe, it can be treated with a blood transfusion,
however this is rarely needed.
 On the other hand, neonates have underdeveloped livers that are
unable to process large amounts of bilirubin and a poorly
developed blood-brain barrier that is unable to block bilirubin from
entering the brain.

 This can result in kernicterus (Chronic Bilirubin Encephalopathy) if left
unchecked.
 If the bilirubin level is sufficiently high as to cause worry, it can be
lowered via phototherapy in the first instance or an exchange
transfusion if severely elevated.
 Phototherapy - Phototherapy is used for cord bilirubin of 3 mg/dl or
higher.
 Some doctors use it at lower levels while awaiting lab results.
 IVIG - Intravenous Immunoglobulin therapy (IVIG) has been used to
successfully treat many cases of HDN.

 It has been used not only on anti-D, but on anti-E as well.
 IVIG can be used to reduce the need for exchange transfusion and
to shorten the length of phototherapy.
 The AAP recommends "In isoimmune hemolytic disease,
administration of intravenous γ-globulin (0.5-1 g/kg over 2 hours) is
recommended if the TSB is rising despite intensive phototherapy
or the TSB level is within 2 to 3 mg/dL (34-51 μmol/L) of the
exchange level .

 Exchange transfusion - Exchange transfusion is used when
bilirubin reaches either the high or medium risk lines on the
normogram provided by the American Academy of Pediatrics
 Cord bilirubin >4mg/dl is also indicative of the need for exchange
transfusion.

 Hemolytic disease of the newborn of Rh, also known
as hemolytic disease of the fetus and newborn, HDN, HDFN,
or erythroblastosis foetalis, is an alloimmune condition that
develops in a fetus at or around birth, when the IgG molecules
(one of the five main types of antibodies) produced by the mother
pass through the placenta.
 Among these antibodies are some which attack antigens on
the red blood cells in the fetal circulation, breaking down and
destroying the cells (hemolysis).

 The fetus can develop reticulocytosis and anemia.
 This fetal disease ranges from mild to very severe, and fetal
death from heart failure (hydrops fetalis) can occur.
 When the disease is moderate or severe,
many erythroblasts (immature red blood cells) are present in
the fetal blood, and so these forms of the disease can be
called erythroblastosis fetalis.

 Signs of hemolytic disease of the newborn include a
positive direct Coombs test (also called direct agglutination test),
elevated cord bilirubin levels, and hemolytic anemia.
 It is possible for a newborn with this disease to
have neutropenia and neonatal alloimmune
thrombocytopenia as well.
 Hemolysis leads to elevated bilirubin levels.

 After delivery bilirubin is no longer cleared (via the placenta) from
the neonate's blood and the symptoms of jaundice (yellowish skin
and yellow discoloration of the whites of the eyes, or icterus)
increase within 24 hours after birth.
 Like other forms of severe neonatal jaundice, there is the
possibility of the neonate developing acute or chronic kernicterus,
however the risk of kernicterus in HDN is higher because of the
rapid and massive destruction of blood cells.

 High or rapidly rising bilirubin in the blood
 Prolonged hyperbilirubinemia
 Bilirubin Induced Neurological Dysfunction
 Cerebral Palsy
 Kernicterus
 Neutropenia
 Thrombocytopenia
 Hemolytic anemia
 Late onset anemia – Must NOT be treated with iron. Can persist up to 12
weeks after birth.

 Antibodies are produced when the body is exposed to
an antigen, foreign to the make-up of the body.
 If a mother is exposed to a foreign antigen and produces IgG (as
opposed to IgM which does not cross the placenta), the IgG will target
the antigen, if present in the fetus, and may affect it in utero and persist
after delivery.
 The three most common models in which a woman becomes sensitized
toward (i.e., produces IgG antibodies against) a particular antigen are
hemorrhage, blood transfusion, and ABO incompatibility.

1. Fetal-maternal hemorrhage, which is the movement of fetal blood
cells across the placenta, can occur during abortion, ectopic
pregnancy, childbirth, ruptures in the placenta during pregnancy (often
caused by trauma), or medical procedures carried out during
pregnancy that breach the uterine wall.
 In subsequent pregnancies, if there is a similar incompatibility in
the fetus, these antibodies are then able to cross the placenta into
the fetal bloodstream to attach to the red blood cells and cause
their destruction (hemolysis).

2. The woman may have received a therapeutic blood transfusion.
 ABO blood group system and the D antigen of the Rhesus (Rh)
blood group system typing are routine prior to transfusion.
3. The third sensitization model can occur in women of blood type O.
 The immune response to A and B antigens, that are widespread in
the environment, usually leads to the production of IgM or IgG anti-
A and anti-B antibodies early in life.

 Anti-D is the only preventable form of HDN.
 Since the 1968, introduction of Rho-D immunoglobulin, (Rhogam),
which prevents the production of maternal Rho-D antibodies, the
incidence of anti-D HDN has decreased dramatically.
 Anti-M also recommends antigen testing to rule out the presence
of HDN as the direct coombs can come back negative in a
severely affected infant.

 Serological types
 Rhesus D hemolytic disease of the newborn (often called Rh disease) is
the most common and only preventable form of severe HDN.
 Rhesus c HDFN can range from a mild to severe disease and is the third
most common form of severe HDN; and more severe if occurred with
Rhesus e.
 Anti-Kell hemolytic disease of the newborn is most commonly caused by
anti-K1 antibodies, the second most common form of severe HDN.

 Blood tests done on the newborn baby
 Biochemistry tests for jaundice including total and direct bilirubin levels.
 Complete blood count (CBC) which may show a decreased hemoglobin
and hematocrit due to red blood cell destruction
 Reticulocyte count which will usually be increased as the bone marrow
makes new red blood cells to replace the ones that are being destroyed.
 Reticulocytosis, and in severe cases erythroblasts (also known as
nucleated red blood cells).
 Positive direct Coombs test (might be negative sometimes)

 Blood tests done on the mother
 Positive indirect Coombs test
 Blood tests done on the mother
 Positive indirect Coombs test

 In cases of Rho(D) incompatibility, Rho(D) immunoglobulin is
given to prevent sensitization.
 However, there is no comparable immunotherapy available for
other blood group incompatibilities
 IVIG – Intravenous Immunoglobulin is used in cases of previous
loss, high maternal titers, known aggressive antibodies at early
pregnancy.

 Plasmapheresis – Plasmapheresis aims to decrease the maternal titer
by direct plasma replacement and physical removal of antibody.
 Plasmapheresis and IVIG together can even be used on women with
previously hydropic fetuses and fetal losses
 IUT – Intrauterine Transfusion (IUT) is done either by intraperitoneal
transfusion (IPT) or intravenous transfusion (IVT).
 IVT is preferred over IPT
 IUTs are only done until 35 weeks

 After birth, treatment depends on the severity of the condition, but could
include temperature stabilization and monitoring, phototherapy,
transfusion with compatible packed red blood, exchange transfusion,
sodium bicarbonate for correction of acidosis and/or assisted ventilation.
 Phototherapy – Exposure to ultraviolet light (phototherapy) is
recommended when the cord bilirubin is 3 or higher (Sometimes lower
levels).
 This converts unconjugated bilirubin to limirubin that is easier for the
infant to clear.

 IVIG - IVIG has been used to successfully treat many cases of
HDN.
 It has been used not only on anti-D, but on anti-E as well
 Exchange transfusion – Exchange transfusion is used when
bilirubin reaches either the high or medium risk lines on the
nonogram provided by the American Academy of Pediatrics

 Other Supportive Rx:
 Treat for seizure secondary to bilirubin encephalopathy
 Oxygen administration
 Adequate breast feeding to help baby clear bilirubin
 Prevent and treat infection that may arise from exchange transfusion
 Maintain fluid balance since baby is on phototherapy

Hemorrhogic Disease of the New-born

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