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Helen Dyson
MBChB MRCPCH
Specialist Registrar in Neonatal Medicine,
A lthough haemophilia might not be
considered a common condition in
neonates, it is the most common inherited
So how does a deficiency of FVIII or FIX
lead to a bleeding problem? Haemostasis
(blood clotting) is a complex process
North Trent Regional Neonatal Unit, Jessop bleeding disorder to present in the during which blood vessels, platelets and
Wing, Sheffield newborn period1. The significant clotting factors interact to minimise
proportion of sporadic cases, the variety of bleeding following tissue injury. Primary
possible bleeding patterns and the haemostasis involves platelets interacting
difficulty in recognising and investigating with the injured vessel wall to form a
neonatal bleeding problems can lead to a primary haemostatic plug. Secondary
delay in diagnosis. Early diagnosis allows haemostasis occurs when clotting factors
for parent education, appropriate are sequentially activated and results in the
treatment and prophylaxis and may also production of thrombin, needed for clot
minimise disability caused by later joint formation5. In haemophilia, primary
and muscle bleeds2. This article will explore platelet plug formation is normal but the
the clinical presentation, diagnosis and deficiency of FVIII or FIX causes impaired
treatment of haemophilia in the newborn. secondary haemostasis resulting in delayed
clot formation and susceptibility to
What is haemophilia? continued bleeding as a result of clots
Haemophilia is an X-linked recessive being abnormally friable. The severity of
bleeding disorder that occurs in 1 in 5,000 the condition is primarily determined by
males, has a worldwide distribution and plasma levels of the deficient factor, which
affects all racial groups3. The condition is are expressed as percentage activity, with
caused by defects in the genes responsible 100% activity being equivalent to 1
for the production of proteins important unit/mL of factor and normal values
in the blood clotting cascade. In ranging from 50-150%6. Severe
haemophilia A, which represents 80-85% haemophilia (<1% activity) almost always
of cases3, defects occur in the gene presents in early life2 with frequent
responsible for the production of a protein spontaneous bleeding. Moderate
Keywords called factor VIII (FVIII), whereas the haemophilia (1-5% activity) can present
defect in haemophilia B affects factor IX with severe bleeding following injury and
haemophilia; bleeding disorder;
(FIX) production, though the two occasional spontaneous bleeds whereas
haemorrhage
conditions are clinically indistinguishable4. mild haemophilia (>5% activity) may
Key points If a female (karyotype XX) inherits an remain undiagnosed or only present with
Dyson, H. (2006) Neonatal haemophilia abnormal copy of the haemophilia gene bleeding after injury or surgery, though
a guide to recognition and management. from one parent, she becomes a carrier but bleeding can still be severe7.
Infant 2(4): 156-59. is not clinically affected because she has a
1. Haemophilia is an important cause of second normal copy of the gene on her Presentation of haemophilia in the
bleeding in the well neonate. other X chromosome. However, a male neonate
2. In carrier mothers the aim should be for (karyotype XY) inheriting an abnormal Bleeding in neonates is not an uncommon
a normal delivery in a haemophilia copy will always be affected as he only has problem. Pulmonary haemorrhage,
centre. one X chromosome. Although gastrointestinal bleeding, bleeding from
3. Significant bleeds need urgent haemophilia can be inherited, it is venepuncture and intraventricular
treatment with recombinant factor VIII.
important to remember that around a haemorrhage occur relatively frequently in
4. Delay in diagnosis is common but can
third of cases occur due to a sporadic preterm infants or term infants with
be avoided by prompt recognition and
mutation of the gene, meaning there will infection or hypoxic-ischaemic injury. In
investigation of abnormal bleeding.
be no family history of the condition1. these circumstances, bleeding usually
Iatrogenic bleeds
Puncture bleeds
occurs as a result of acquired conditions FIGURE 1 Spontaneous haematoma.
such as thrombocytopaenia or As haemophilia causes a delay in clot
disseminated intravascular coagulation it is estimated to occur in 1 to 4% of formation, routine procedures may result
(DIC), and infants are often unwell. In neonates with haemophilia3. ICH in the in excessive bruising or haematoma
contrast, haemophilia often presents as neonatal period is thought to be related to formation. Problems can occur after
unexplained bleeding in an otherwise well birth trauma, so usually presents within venepuncture, intramuscular injection
infant8. the first week of life with signs of acute (vitamin K administration or
So how can an infant with haemophilia hypovolaemia, non-specific symptoms immunisation), arterial puncture or heel
be identified? In some infants, there will be such as lethargy and vomiting or more prick blood sampling. Excessive bleeding
a family history of haemophilia in which specific neurological signs such as after any of these procedures should
case the mother ought to have had her hypertonia or seizures4. Although cranial warrant consideration of haemophilia or
carrier status tested and the infant will be ultrasound detects some cases, CT may be another clotting disorder as a diagnosis.
tested routinely after birth. However, in required to identify subdural or posterior Circumcision
cases where there is no family history, fossa bleeds. The diagnosis is important
diagnosis will be made after an iatrogenic In some reviews, post-circumcision
because 40-60% of infants with
or spontaneous bleed, with 30-60% of bleeding is cited as a common presentation
haemophilia and an ICH go on to have
individuals being diagnosed within the of haemophilia, accounting for up to 30%
neurological sequelae including seizures,
neonatal period2,3,9. Since identification of of cases3, though it is important to
learning difficulty or persisting
cases after a bleed still represents a large remember that circumcision is performed
neurological signs10,11. While some
proportion of diagnoses and bleeding more commonly in the US than in
recommend that FVIII levels be checked in
patterns are different from those in older Europe2. Nevertheless, post-circumcision
all term male infants presenting with an
children (who present with joint and bleeding ought to be investigated if it is
ICH12, even when this is done, an
muscle bleeds), identification of bleeding deemed excessive.
alternative initial diagnosis (such as sepsis
patterns in neonatal haemophilia remains or meningitis) may be made, despite
important9.
Management of pregnancy in
clotting screen results being consistent with
A variety of presentations have been carrier mothers
a diagnosis of haemophilia11.
described in the literature but as much of If a mother is known to be a carrier of
the data is from case reports, it can be Extracranial bleeds haemophilia, pregnancy and labour can be
difficult to identify the true incidence of Bleeding outside the cranial cavity can managed in a way which reduces the risk
each presentation. However, the reported occur below the periosteum lining the of adverse events for the mother and baby.
presentations can be divided into outside of the skull bones Issues to consider include place of delivery,
spontaneous or iatrogenic bleeds, with (cephalohaematoma) or below the galea antenatal counselling and diagnosis,
some reporting iatrogenic bleeds as being aponeurotica (subgaleal), a thin tendonous management of delivery and care of the
more common as a presenting bleed in sheath in the scalp. Although neurological infant after birth.
infants under one month of age and sequelae are unusual in extracranial
spontaneous bleeds being more common haemorrhage (ECH), large amounts of Place of delivery
later in infancy9. blood can be lost, leading to a mortality Mothers who are known carriers of
rate of up to 22% in subgaleal bleeds13, so haemophilia should be booked to deliver
Spontaneous bleeds prompt recognition and resuscitation are in an obstetric unit at a haemophilia
Intracranial haemorrhage required. ECH can occur concurrently centre for both their own and their childs
Although the true incidence of intracranial with an ICH, the cumulative incidence of benefit. Carrier mothers, although not
haemorrhage (ICH) is probably unknown ICH and ECH being reported as 3.58% in normally clinically affected, may have
due to under-reporting and misdiagnosis, the neonatal period10. relatively low FVIII or FIX levels,
to avoid giving their child non-steroidal 24 hours and some haemostatic efficacy for Livingstone.
5. Buchanan, G.R. Coagulation disorders in the neonate.
anti-inflammatory medication as it can up to 72 hours. Some authors recommend
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