Download Hemolytic disease of the newborn - Easymed.club

Dnipropetrovsk Medical Institute of
Conventional and Alternative
Medicine
Current Methods of
Diagnosis and
Treatment
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Haemolytic diseases are those conditions in which the red
cells of the individual do not survive normally in vivo.
Haemolysis lead to red cell destruction and may be
associated with anaemia.
If red cell destruction occur inside the blood vessels it is
called intravascular haemolysis.
Intravascular haemolysis is mediated by complement
activation and results in free hemoglobin (Hb) in
circulation (not good for the kidney).
Red cell destruction in the Reticulo-endothelial system
(e.g. Liver and spleen) is known as extravascular
haemolysis (e.g. aged red cells).
Extravascular haemolysis is macrophage mediated red
cell destruction.
The liver is vital for the removal of toxic metabolites which
are produced following red cell haemolysis.
1) Intravascular haemolysis:
• Releases free hemoglobin which is toxic to the
kidney.
• Hb is immediately bound by haptoglobin in the
plasma.
• Hb-haptoglobin complex is removed by hepatic
cells.
2) Extravascular haemolysis:
• Free Hb
haem molecules
bilirubin.
• Free unconjugated bilirubin is transported to the
liver where it is conjugated to glucuronic acid and
eventually removed ( in faeces).
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Foetus liver cannot metabolise bilirubin which is
toxic (cannot be filtered by kidney and can
damage the brain tissues).
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Bilirubin in fetal circulation is transferred to the
mother circulation for its excretion.
- Newborn baby liver enzymes are not functioning
before day 10 post-delivery
P
N
Blood film of a fetus affected by HDN showing polychromasia
and increased number of normaoblasts
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Antibodies against
 Anti-D and less commonly anti-c, anti-E
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Mother is the case of anti-D is Rh -ve (negative)
Firstborn infant is usually unaffected
Sensitization of mother occurs
 During gestation
 At the time of birth
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All subsequent offspring inheriting D-antigen will be
affected in case of anti-D HDN
Pathogenesis
Fetomaternal Hemorrhage
Maternal Antibodies formed against Paternally
derived antigens
During subsequent pregnancy, placental passage of
maternal IgG antibodies
Maternal antibody attaches to fetal red blood cells
Fetal red blood cell hemolysis
• HDFN is triggered by maternal antibodies to paternally inherited
antigens in the fetus.
• The most frequently described antibody in HDFN is the RhD
antibody.
• If the mother is RhD negative and the father is RhD positive the
baby may inherit the D antigen and express it on fetal RBC.
• Fetal red cells (RhD +) enter the maternal circulation as a result of
fetomaternal haemorrhage (FMH) at the time of delivery.
• The mother immune system reacts and form anti-D antibodies for
many years.
• Second pregnancy: Maternal IgG anti-D crosses the placenta and
sensitizes the D+ fetal cells.
Synthesised fetal RBCs are removed from fetal circulation and
destroyed by macrophages in the Reticulo-endothelial system .
• This cause severe anaemia and referred to as erythroblastosis
fetalis.
• During pregnancy, excess free bilirubin is transported to mother
for metabolism and excretion.
• Severe fetal anaemia causes edema of the fetal liver and spleen,
which are the organs for both erythropoiesis and cell destruction.
• In the most severe cases of HDFN, Hydrops fetalis (severe
oedema) may result in intrauterine death and stillbirth.
• At delevery the maternal system is no longer available to remove and
excrete bilirubin & neonatal liver is not fully functioning free toxic
bilirubin can damage the brain (kernicterus).
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Antigenic exposure
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Host factors
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Antibody specificity
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Influence of ABO group
 ABO-incompatible Rh- positive cells will be hemolysed
before Rh antigen can be recognized by the mother’s
immune system
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HDFN occurs very frequently due to ABO
incompatibility between the mother and the fetus.
• The ABO antibodies in the maternal blood are IgG
anti- A,B in a group O mother carrying a group A or
B fetus.
• This type of HFDN does not cause problem to the
fetus in the uterus but may cause jaundice and mild
anaemia post-delivery.
• The disease usually requires special treatment such as
phototherapy and/ or the administration of
immunoglobulin.
• Maternal anti-D is the most frequent cause of Rh
HDFN and causes the most severe cases of Rh
HDFN, followed by anti-c.
• The other antibodies within the Rh system may
also be implicated, in addition to combinations
of antibodies, e.g. anti-C plus anti-D, anti-C plus
anti-e, or anti-c plus anti-E.
• Pregnant woman blood should be sent to the lab for
antenatal screening tests:
1- ABO grouping.
2-Rh typing.
3- antibody screening.
4- antibody identification.
• Parental red cell typing
• Fetal amniocentesis & Doppler technique
Postnatal tests for HDFN
• Hemolytic disease of the newborn (also known as HDN or
erythroblastosis fetalis)
– Rh D hemolytic disease of the newborn (also known as Rh
disease)
– ABO hemolytic disease of the newborn (the indirect Coombs
test may only be weakly positive)
– Anti-Kell hemolytic disease of the newborn
– Rh c hemolytic disease of the newborn
– Rh E hemolytic disease of the newborn
– Other blood group incompatibility (RhC, Rhe, Kidd, Duffy,
MN, P and others)
• Alloimmune hemolytic transfusion reactions
• Warm antibody autoimmune hemolytic anemia
– Idiopathic
– Systemic lupus erythematosus
– Evans' syndrome (antiplatelet antibodies and
hemolytic antibodies)
• Cold antibody autoimmune hemolytic anemia
– Idiopathic cold hemagglutinin syndrome
– Infectious mononucleosis
– Paroxysmal cold hemoglobinuria
• Methyldopa (IgG mediated type II
hypersensitivity)
• Penicillin (high dose)
• Quinidine (IgM mediated activation of classical
complement pathway and Membrane attack
complex, MAC)
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List the classifications of Hemolytic Disease of the
Newborn and the most antibody specificities
involved.
State the testing to perform on the mother to monitor
the severity of HDN.
List the laboratory tests and values which indicate
that an infant is affected by HDN both in the fetus
and newborn.
State the treatment options for intrauterine treatment
of HDN.
State the treatment options for HDN in the
moderately and severely affected newborn.
State the requirements of blood to be used for
transfusion of the fetus and newborn.
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Maternal IgG antibodies directed against an
antigen of paternal origin present on the fetal
red blood cells.
IgG antibodies cross the placenta to coat fetal
antigens, cause decreased red blood cell
survival which can result in anemia.
Produced in response to previous pregnancy
with antigen positive fetus OR exposure to red
blood cells, ie transfusion.
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ABO
“Other” – unexpected immune antibodies other
than anti-D – Jk, K, Fy, S, etc.
Rh – anti-D alone or may be accompanied by
other Rh antibodies – anti-C, -c, -E or –e.
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Mother group O, baby A or B
Group O individuals have anti-A, -B and –A,B
in their plasma, fetal RBCs attacked by 2
antibodies
Occurs in only 3%, is severe in only 1%, and
<1:1,000 require exchange transfusion.
The disease is more common and more severe
in African-American infants.
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Uncommon, occurs in ~0.8% of pregnant
women.
Immune alloantibodies usually due to anti-E, c, -Kell, -Kidd or -Duffy.
Anti-K
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disease ranges from mild to severe
over half of the cases are caused by multiple blood
transfusions
is the second most common form of severe HDN
Anti-M very rare
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Anti-D is the commonest form of severe HDN.
The disease varies from mild to severe.
Anti-E is a mild disease
Anti-c can range from a mild to severe disease is the third most common form of severe HDN
Anti-e - rare
Anti-C - rare
antibody combinations (ie anti-c and anti-E
antibodies occurring together) - can be severe
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Maternal antibodies destroy fetal red blood cells
 Results in anemia.
 Anemia limits the ability of the blood to carry
oxygen to the baby's organs and tissues.
Baby's responds to the hemolysis by trying to make
more red blood cells very quickly in the bone marrow
and the liver and spleen.
 Organs enlarge - hepatosplenomegaly.
 New red blood cells released prematurely from bone
marrow and are unable to do the work of mature red
blood cells.
As the red blood cells break down, bilirubin is formed.
 Babies unable to get rid of the bilirubin.
 Builds up in the blood (hyperbilirubinemia ) and
other tissues and fluids of the baby's body resulting
in jaundice.
 The placenta helps get rid of some of the bilirubin,
but not all.
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Severe anemia with enlargement of the liver and
spleen
When these organs and the bone marrow cannot
compensate for the fast destruction of red blood cells,
severe anemia results and other organs are affected.
Hydrops Fetalis
This occurs as the baby's organs are unable to handle
the anemia. The heart begins to fail and large amounts
of fluid build up in the baby's tissues and organs. A
fetus with hydrops is at great risk of being stillborn.
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Varies from mild jaundice and anemia to hydrops fetalis (with
ascites, pleural and pericardial effusions)
Chief risk to the fetus is anemia.
Extramedullary hematopoiesis due to anemia results in
hepatosplenomegaly.
Risks during labor and delivery include:
 asphyxia and splenic rupture.
Postnatal problems include:
 Asphyxia
 Pulmonary hypertension
 Pallor (due to anemia)
 Edema (hydrops, due to low serum albumin)
 Respiratory distress
 Coagulopathies (↓ platelets & clotting factors)
 Jaundice
 Kernicterus (from hyperbilirubinemia)
 Hypoglycemia (due to hyperinsulinemnia from islet cell
hyperplasia)
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Kernicterus (bilirubin encephalopathy) results
from high levels of indirect bilirubin (>20
mg/dL in a term infant with HDN).
Kernicterus occurs at lower levels of bilirubin
in the presence of acidosis, hypoalbuminemia,
prematurity and certain drugs (e.g.,
sulfonamides).
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Affected structures have a bright yellow color.
Unbound unconjugated bilirubin crosses the blood-brain
barrier and, because it is lipid soluble, it penetrates neuronal and
glial membranes.
Bilirubin is thought to be toxic to nerve cells
The mechanism of neurotoxicity and the reason for the
topography of the lesions are not known.
Patients surviving kernicterus have severe permanent neurologic
symptoms (choreoathetosis, spasticity, muscular rigidity, ataxia,
deafness, mental retardation).
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Vary with severity of HDN and include:
Anemia
Hyperbilirubinemia
Reticulocytosis (6 to 40%)
↑ nucleated RBC count (>10/100 WBCs)
Thrombocytopenia
Leukopenia
Positive Direct Antiglobulin Test
Hypoalbuminemia
Rh negative blood type or ABO incompatibility
Smear: polychromasia, anisocytosis, no spherocytes
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Polychromasia
Anisocytosis
Increase NRBCs
no spherocytes
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Total Serum Bilirubin (TSB) monitored to determine
risk of kernicterus.
Measure bilirubin in cord blood and at least every 4
hours for the first 12 to 24 hours. Plot bilirubin
concentrations over time.
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Transcutaneous bilirubinometry can be adopted as the
first-line screening tool for jaundice in well, full-term
babies.
This leads to about 50% decrease in blood testing.
http://tinyurl.com/36jazx
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Given to the fetus to prevent hydrops fetalis and fetal
death.
Can be done as early as 17 weeks, although preferable
to wait until 20 weeks
Severely affected fetus, transfusions done every 1 to 4
weeks until the fetus is mature enough to be delivered
safely. Amniocentesis may be done to determine the
maturity of the fetus's lungs before delivery is
scheduled.
After multiple IUTs, most of the baby’s blood will be D
negative donor blood, therefore, the Direct
Antiglobulin test will be negative, but the Indirect
Antiglobulin Test will be positive.
After IUTs, the cord bilirubin is not an accurate
indicator of rate of hemolysis or of the likelihood of the
need for post-natal exchange transfusion.
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An intrauterine fetal blood transfusion is done in the
hospital. The mother may have to stay overnight after the
procedure.
The mother is sedated, and an ultrasound image is obtained
to determine the position of the fetus and placenta.
After the mother's abdomen is cleaned with an antiseptic
solution, she is given a local anesthetic injection to numb the
abdominal area where the transfusion needle will be
inserted.
Medication may be given to the fetus to temporarily stop
fetal movement.
Ultrasound is used to guide the needle through the mother's
abdomen into the fetus's abdomen or an umbilical cord vein.
A compatible blood type (usually type O, Rh-negative) is
delivered into the fetus's abdominal cavity or into an
umbilical cord blood vessel.
The mother is usually given antibiotics to prevent infection.
She may also be given tocolytic medication to prevent labor
from beginning, though this is unusual.
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Increasingly common and relatively safe procedure since the
development of high resolution ultrasound particularly with
colour Doppler capability.
MCA Doppler velocity as a reliable non-invasive screening tool to
detect fetal anemia.
 The vessel can be easily visualized with color flow Doppler as
early as 18 weeks’ gestation.
 In cases of fetal anemia, an increase in the fetal cardiac output
and a decrease in blood viscosity contribute to an increased
blood flow velocity
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The risk of these
procedures is now
largely dependent
on the prior
condition of the
fetus and the
gestational age at
which transfusion is
commenced.
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Titer greater than 32 for anti-D and 8 for anti-K OR four fold
increase in titer indicates need for analysis of amniotic fluid.
Amniocentesis
 Perform at 28 wks if HDN in previous child
 Perform at 22 wks if previous child severely affected
 Perform if maternal antibody increases before 34th wk.
High values of bilirubin in amniotic fluid analyses by the Liley
method or a hemoglobin concentration of cord blood below 10.0
g/mL.
Type fetus -recent development in fetal RhD typing involves the
isolation of free fetal DNA in maternal serum. In the United
Kingdom, this technique has virtually replaced amniocentesis for
fetal RhD determination in the case of a heterozygous paternal
phenotype
Maternal plasma exchange may be instituted if the fetus is too
young for intrauterine transfusion.
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CPD, as fresh as possible, preferably <5 days old.
A hematocrit of 80% or greater is desirable to minimize
the chance of volume overload in the fetus.
The volume transfused ranges from 75-175 mL
depending on the fetal size and age.
CMV negative
Hemoglobin S negative
IRRADIATED
O negative, lack all antigens to which mom has
antibodies and Coomb’s compatible.
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Phototherapy is the treatment of choice.
Phototherapy process slowly
decomposes/converts bilirubin into a nontoxic
isomer, photobilirubin, which is transported in
the plasma to the liver.
HDN is judged to be clinically significant
(phototherapy treatment) if the peak bilirubin
level reaches 12 mg/dL or more.
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The therapy uses a blue light (420-470 nm) that converts
bilirubin so that it can be excreted in the urine and feces.
Soft eye shields are placed on the baby to protect their eyes
from damage that may lead to retinopathy due to the bili
lights.
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Lightweight, fiberoptic pad delivers up to 45
microwatts of therapeutic light for the treatment of
jaundice while allowing the infant to be swaddled,
held and cared for by parents and hospital staff.
Compact unit is ideal for hospital and homecare.
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Full-term infants rarely require an exchange
transfusion if intense phototherapy is initiated
in a timely manner.
It should be considered if the total serum
bilirubin level is approaching 20 mg/dL and
continues to rise despite intense in-hospital
phototherapy.
The procedure carries a mortality rate of
approximately 1% and there may be substantial
morbidity
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Remove sensitized cells.
Reduce level of maternal antibody.
Removes about 60 percent of bilirubin from the
plasma, resulting in a clearance of about 30
percent to 40 percent of the total bilirubin.
Correct anemia by providing blood that will
have normal survival.
Replacement with donor plasma restores
albumin and any needed coagulation factors.
Rebound – usually a 2 volume exchange is
needed as bilirubin in tissues will return to
blood stream.
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Antibody elution testing from cord red blood cells.
ABO/D typing
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If baby received intrauterine transfusions will type as O
negative
If baby’s Direct Antiglobulin Test is strongly positive due to
anti-D may get FALSE NEGATIVE immediate spin reaction
with reagent anti-D (blocking phenomenon), weak D (Du) test
will be STRONGLY positive
Antibody screen
Coomb’s crossmatch antigen negative donor.
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Type and screen on mom.
Identification of unexpected antibodies.
More than 40 antigens have been identified as
causing HDN.
Select blood that lacks antigens to which mom
has antibodies.
Perform coomb’s crossmatch with Mom and
baby’s blood.
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CPD, as fresh as possible, preferably <5
days old.
CMV negative
Hemoglobin S negative
Irradiated if possible
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Physician will specify a hematocrit.
Reconstitute donor unit with plasma.
Most facilities prefer to use group O red
cells and AB plasma.
Reference for procedure at end of this
presentation.
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Three types of HDN vary in severity.
Laboratory testing key to diagnosing and
monitoring- great care to be taken when
interpreting ABO/D typing on affected
infants.
Therapy dependent on severity:
phototherapy alone or with transfusion.
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