Haemolytic Disease of the Fetus and Newborn
(HDFN)
BMS5203 Blood & Cellular Sciences
Amanda Davies
HDFN
Anti-D : Aetiology of HDFN
• Most common cause of severe
haemolytic disease of the foetus
and newborn (HDN)
• Effects are severe, can cause foetal
death
• Prevalence of HDN due to anti-D
substantially decreased by
prophylaxis
Incidence in the UK..
Pre 1969 (Intro of anti-D prophylaxis)
1% of all newborns affected by HDN
Cause of death for 1 in every 2200 births
NICE 2011 Data
500 fetuses develop HDN each year
25-30 babies die, 20 miscarriages and 45 children that are
affected will suffer developmental problems (BMJ, 2005)
Erythroblastosis fetalis -HDFN
Hemolytic disease of the fetus and
newborn (HDFN) is a destruction of the
red blood cells (RBCs) of the fetus and
neonate by antibodies produced by the
mother
It is a condition in which the life span of
the fetal/neonatal red cells is shortened
due to maternal allo-antibodies reacting
against red cell antigens acquired from
the father
Hemolytic Disease of Newborn (A.K.A.
Erythroblastosis fetalis)
Some of the infant's blood may enter the
maternal circulation during a fetomaternal
haemorrhage, causing the formation of
antibodies against the fetal red blood cells.
The first baby is usually not harmed. WHY?
If the mother's antibodies pass into the
circulation of subsequent fetuses, they may
destroy the fetal red blood cells, causing the
severe hemolytic disease of newborns
erthyroblastosis fetalis.
The probability of this situation occurring is high
if the father is RhD Positive.
Pathophysiology
PRIMARY RESPONSE - After initial exposure to foreign antigen,
the maternal immune system produces IgM antibodies that
do not cross placenta.
SECONDARY RESPONSE - Later, IgG antibodies are produced
that can traverse placental barrier. Normally the IgG anti-D
antibody does not reach a significant level during the first
pregnancy to cause significant destruction of fetal/neonatal
red cells.
A repeat exposure to the same antigen during a subsequent
pregnancy rapidly induces IgG production (0.03ml of Rh+ve
red cells)
Pathophysiology
• After sensitisation, maternal IgG anti-D antibodies cross
placenta
• Attach to RhD antigen on foetal red cells
• Antibody coated RBC’s lysed…. How?
• Prolonged haemolysis – severe anaemia
• Heme released and converted into unconjugated bilirubin
Pathogenesis of the Disease
• Severe anaemia as a result of
RBC destruction giving rise to
tachycardia.
• Due to compensatory
extramedullary haemopoiesis,
liver production of proteins
decreased.
• Cardiac insufficiency and
reduced α-fetoprotein leads to
hypotension, oedema and
ascites.
• Tissue oxygenation reduced to
vital organs
Hemolytic disease of the fetus and newborn
HDFN
Before birth
Anaemia (destruction of red cells)
Heart failure
Hydrops fetalis
Fetal death
After birth
Anaemia (destruction of red cells)
Heart failure
Build up of bilirubin which can result in Kernicterus
Severe growth retardation
Diagnostic testing
All pregnant women screened for the presence of red cell antibodies
during early and late pregnancy.
When present, antibody levels are determined and monitored to identify
sudden changes which would indicate problems for the fetus.
D d
Paternal sampling – phenotype and zygosity testing
d Dd dd
Foetal blood type (amniotic fluid/maternal circulation)
d Dd dd
Indicators for severe HDN include:
D D
• Previous children with haemolytic disease
• Rising maternal antibody titres d Dd Dd
• Rising amniotic fluid bilirubin concentration
• Ultrasound (hydrops & Mid cerebral velocity MCV) d Dd Dd
HDFN Lab Findings at Birth
Cord Blood
Variable anaemia (Hb<16g/dl)
Reduced RBC count
High reticulocytes, possibly erythroblasts (nucleated red cells)
Baby RhD+ve
Raised serum bilirubin
Spherocytes on the peripheral blood film
Direct Antiglobulin Test is positive – what is this?
Anti-D detectable in babies plasma
Reduced total protein in plasma
Mum
RhD-ve with high plasma levels anti-D
Direct Antiglobulin Test
• Test performed on red cells to determine whether the
cells have been coated with antibody in vivo
• Test utilises an anti-human globulin reagent to detect the
presence of antibodies bound to the surface of red cells.
• Cells can be DAT positive in the following instances:
– HDFN when maternal antibody has crossed the placenta and
bound to incompatible fetal antigens most commonly RhD
– Following incompatible transfusion when the transfused donor
cells are sensitized with patient’s antibody
– If a patient has an autoimmune condition and is producing
antibodies (therefore autoantibodies) to their own cells.
Antenatal Prophylaxis
1953- Chown confirmed pathogenesis of Rh alloimmunisation
to be the result of passage of Rh+ve foetal RBC after
transplacental haemorrhage
1966 – Anti-D immunoglobulin prophylaxis (RhIgG
prophylaxis) prevents sensitisation of Rh-ve women….. What
is this?
1971 – WHO makes recommendations as to dosage
Routine use of RhIgG prophylaxis resulted in significant
decline in incidence of RhD alloimmunisation – now rare
Prevention of Rh-D Immunisation
• Anti-D is now given to every Rh-D negative woman
giving birth to a Rh-D positive child.
• Kleihauer testing estimates the severity of Fetal
Maternal Hemorrage, confirmation of significant bleeds
by flow cytometry (>2mls)
• The size of bleed can be estimated and the anti-D
dosage can be altered (increased if >4ml).
Estimation of the size of
Fetomaternal Haemorrhage
Prophylactic Anti-D Dosing
• Less than 12 weeks gestation: No anti-D
required
• Less than 20 weeks gestation: Standard
dose of 250iu anti-D
• 20 – 40 weeks : Estimate level of
prophylactic anti-D required using
Kleihauer or Flow cytometry technique.
