state of the art review
How I manage neonatal thrombocytopenia
Subarna Chakravorty1,2 and Irene Roberts1,2
1
Centre for Haematology, Imperial College London, London, and 2Department of Paediatrics, St Mary’s Hospital, Imperial College
Healthcare NHS Trust, London, UK
Summary
Although neonatal thrombocytopenia (platelet count < 150
· 109/l) is a common finding in hospital practice, a careful
clinical history and examination of the blood film is often
sufficient to establish the diagnosis and guide management
without the need for further investigations. In preterm
neonates, early-onset thrombocytopenia (<72 h) is usually
secondary to antenatal causes, has a characteristic pattern and
resolves without complications or the need for treatment. By
contrast, late-onset thrombocytopenia in preterm neonates
(>72 h) is nearly always due to post-natally acquired bacterial
infection and/or necrotizing enterocolitis, which rapidly leads
to severe thrombocytopenia (platelet count < 50 · 109/l).
Thrombocytopenia is much less common in term neonates
and the most important cause is neonatal alloimmune
thrombocytopenia (NAIT), which confers a high risk of
perinatal intracranial haemorrhage and long-term neurological
disability. Prompt diagnosis and transfusion of human platelet
antigen-compatible platelets is key to the successful manage-
ment of NAIT. Recent studies suggest that more than half of
neonates with severe thrombocytopenia receive platelet trans-
fusion(s) based on consensus national or local guidelines
despite little evidence of benefit. The most pressing problem in
management of neonatal thrombocytopenia is identification of
safe, effective platelet transfusion therapy and controlled trials
are urgently needed.
Keywords: neonatal thrombocytopenia, neonatal alloimmune
thrombocytopenia, platelet transfusion, immune thrombocy-
topenia, platelets.
Thrombocytopenia is one of the commonest haematological
disorders in the neonatal period, affecting up to a third of
those admitted to neonatal intensive care units (reviewed in
(Roberts et al, 2008; Sola-Visner et al, 2008). In most cases a
careful clinical history and a limited number of straightforward
Correspondence: Irene Roberts, Centre for Haematology,
Hammersmith Campus, Imperial College London, Du Cane Road,
London W12 0NN, UK.
E-mail: irene.roberts@imperial.ac.uk
ª 2011 Blackwell Publishing Ltd, British Journal of Haematology, 156, 155–162
investigations is sufficient to establish the diagnosis and guide
management. The majority of episodes of neonatal thrombo-
cytopenia are relatively mild, self-limiting and of short
duration (Murray & Roberts, 1996; Murray et al, 2002;
Stanworth et al, 2009). However, 5–10% of cases are more
severe and/or prolonged and require specialist investigations
(Murray & Roberts, 1996; Murray et al, 2002) and preterm
neonates have one of the highest rates of intracranial
haemorrhage (ICH), which affects up to a quarter of those
with low birth weight (Lemons et al, 2001; von Lindern et al,
2011). This review briefly discusses the definition, prevalence
and causes of neonatal thrombocytopenia and describes our
practical approach to investigation and management, includ-
ing neonatal alloimmune thrombocytopenia (NAIT) and the
role of platelet transfusion.
Definition of thrombocytopenia in neonates
Previous studies have shown that the fetal platelet count
reaches 150 · 109/l by the end of the first trimester of
pregnancy (Van den Hof & Nicolaides, 1990; Pahal et al,
2000) and is maintained at or above this level to term in
healthy fetuses (Forestier et al, 1986, 1991). These data indicate
that neonatal thrombocytopenia can be defined as a platelet
count < 150 · 109/l in any healthy neonate of a viable
gestational age. This definition is certainly reliable for term
neonates where large population studies that show that >98%
of term neonates have a platelet count > 150 · 109/l at birth
(Burrows & Kelton, 1990a, 1993, 1995; Sainio et al, 2000). On
the other hand, a recent very large population-based study
reported that in preterm infants, particularly those of
extremely low gestation (22–24 weeks), platelet counts may
be as low as 100 · 109/l in the first few days of life (Wiedmeier
et al, 2009). However, as such studies include a spectrum of
neonates, many of which are likely to have identifiable causes
for their low platelet count, we continue to use a platelet count
of 150 · 109/l as the threshold for defining neonatal throm-
bocytopenia and guiding investigations in neonates of all
gestations.
Neonatal thrombocytopenia is generally defined as severe
when the platelet count is less than 50 · 109/l based on clinical
experience of a high incidence of life-threatening haemorrhage
First published online 27 September 2011
doi:10.1111/j.1365-2141.2011.08892.x
Review

and guided by a pilot-tested data collection form designed as a

bleeding ‘assessment tool’ to objectively measure the frequency
of major haemorrhage (e.g. pulmonary, intraventricular) and
minor haemorrhage (e.g. petechiae, haematuria) in thrombo-
cytopenic neonates (Stanworth et al, 2009). The frequency of
major haemorrhage varies depending upon a number of
clinical factors, particularly birth weight and gestational age at
birth. Both prospective and retrospective studies suggest that
the most common site of major haemorrhage in neonates is
intracranial (particularly intraventricular),which is docu-
mented in c. 5% of all thrombocytopenic neonates, while
gastrointestinal haemorrhage occurs in 1–5%, pulmonary
haemorrhage in 0Æ6–5% and haematuria in 1–2% of throm-
bocytopenic neonates (Baer et al, 2009; Gerday et al, 2009;
Stanworth et al, 2009).
Fig 1. Diagnostic algorithm for investigation of preterm neonates with
thrombocytopenia. NEC, necrotizing enterocolitis; NAIT, neonatal
Prevalence of neonatal thrombocytopenia alloimmune thrombocytopenia.
Estimates of the prevalence of thrombocytopenia vary from
<1% to 80% depending upon the characteristics of the
population studied (Castle et al, 1986; Sainio et al, 2000; Platelet count < 150 × 109/l
Christensen et al, 2006; Baer et al, 2009; von Lindern et al,
2011; Rastogi et al, 2011). The strongest predictors for the
Bleeding Incidental finding
development of neonatal thrombocytopenia are gestational age
at birth and whether or not neonates born after complicated
and/or ‘high risk’ pregnancies are included (Sainio et al, 2000). Test for NAIT Platelets < 50 × 109/l Platelets > 50 × 109/l
The highest prevalence of thrombocytopenia is seen in Coagulation tests

neonatal intensive care units where 22–35% of all admissions

have at least one episode of neonatal thrombocytopenia during
their admission (Roberts et al, 2008; Sola-Visner et al, 2008), Consider:

particularly in very low birth weight preterm neonates in NAIT No NAIT NAIT
which a prevalence of 70–80% has been reported (Mehta et al, Spurious thrombocytopenia
(common in polycythaemia)
1980; Ferrer-Marin et al, 2010). Fortunately, most cases are Autoimmune causes
relatively mild and the prevalence of severe thrombocytopenia Exclude DIC Aneuploidy.
Congenital thrombocytopenia If thrombocytopenia persists
in several studies is fairly consistently reported at between Bacterial or viral infection >10 d, exclude rarities
2Æ4% and 10% (Christensen et al, 2006; Roberts et al, 2008; Autoimmune causes

Baer et al, 2009; von Lindern et al, 2011). Nevertheless, it is

Fig 2. Diagnostic algorithm for investigation of term neonates with
these neonates who need urgent investigation to identify the
thrombocytopenia. NAIT, neonatal alloimmune thrombocytopenia;
cause, particularly those cases due to NAIT (see below). DIC, disseminated intravascular coagulation.

Causes of thrombocytopenia
Causes of neonatal thrombocytopenia can usually be deter-
mined by the clinical history and presentation. In particular,
the gestation of the baby, the timing of the onset of
thrombocytopenia, maternal and neonatal history and the full
blood count and blood film appearances can be used to
identify the cause in the vast majority of neonates and
incorporated into a diagnostic algorithm for preterm (Fig 1)
and term (Fig 2) neonates (discussed below). This approach
has been used successfully in our centre since 1990 and relies
on a close dialogue between the neonatologists and haematol-
ogists, together with making blood films routine for all
neonatal samples, which, in our experience, often obviates the
need for expensive further investigations. The age of onset of
thrombocytopenia is an extremely important predictor of the
likely cause. The most common causes of thrombocytopenia
presenting in the first 72 h of life, and occasionally in fetal life,
are almost all related to complications of pregnancy and/or
delivery (Table I). (Murray & Roberts, 1996; Watts & Roberts,
1999; Watts et al, 1999). By contrast, the vast majority of
neonates developing thrombocytopenia after the first 72 h of
life do so as a result of a post-natally acquired bacterial
infection and/or necrotizing enterocolitis (Table I) (Watts &
Roberts, 1999).
Although a number of methods for assessing neonatal
platelet production, such as serum thrombopoietin, megak-
aryocyte progenitor numbers, mean platelet volume (MPV),
the immature platelet fraction and reticulated platelet counts

156 ª 2011 Blackwell Publishing Ltd, British Journal of Haematology, 156, 155–162
 Review

Table I. Causes of neonatal thrombocytopenia.

Early-onset (<72 h)
Chronic fetal hypoxia (e.g. PIH, IUGR,
diabetes)
Perinatal asphyxia
Perinatal infection (e.g. Escherichia coli,
Group B streptococcus)
Disseminated intravascular coagulation
Neonatal alloimmune thrombocytopenia
(NAIT)
Neonatal autoimmune thrombocytopenia
(e.g. ITP, SLE)
Congenital infection (e.g. CMV,
toxoplasma, rubella, Coxasckie virus)
Thrombosis (e.g. aortic, renal vein)
Fig 3. Peripheral blood film from a preterm neonate with thrombo-
Bone marrow replacement (e.g. congenital
cytopenia secondary to intrauterine growth restriction (IUGR) show-
leukaemia)
ing closely packed red cells reflecting the high haematocrit, increased
Kasabach-Merritt syndrome nucleated red blood cells and a Howell-Jolly body (inset). There is also
Metabolic disease (e.g. proprionic and associated neutropenia.
methylmalonic acidaemia)
Inherited (e.g. Congenital amegakaryocytic
thrombcytopenia IUGR and easy to identify. The platelet count usually falls to a
Late-onset (>72 h) Late-onset sepsis nadir of >50 · 109/l 4–7 d after birth before spontaneously
Necrotizing enterocolitis recovering within 10 d; affected neonates also have several
Congenital infection (e.g. CMV, associated haematological abnormalities that help to confirm
toxoplasma, rubella, Coxsackie virus)
the diagnosis, including transient neutropenia, increased
Autoimmune
numbers of circulating nucleated red cells with or without
Kasabach-Merritt syndrome
Metabolic disease (e.g. proprionic and
associated polycythaemia, and Howell-Jolly bodies (Fig 3)
methylmalonic acidaemia) (Murray & Roberts, 1996; Watts & Roberts, 1999; Watts et al,
Inherited (e.g. Congenital amegakaryocytic 1999). Early onset thrombocytopenia secondary to placental
thrombocytopenia) insufficiency is always self-limiting and therefore further
investigation of such cases is unnecessary provided the platelet
CMV, cytomegalovirus; ITP, idiopathic thrombocytopenic purpura; count remains > 50 · 109/l and recovers within 2 weeks
SLE, systemic lupus erythematosus; PIH, pregnancy-induced hyper-
(Fig 1).
tension; IUGR, intrauterine growth restriction.
The next most common causes of early onset thrombocy-
The most frequently occurring conditions are shown in bold type.
topenia in preterm neonates are severe perinatal hypoxia (e.g.
hypoxic ischaemic encephalopathy), which is often associated
have been described in the literature in order to investigate with disseminated intravascular coagulation (DIC); perinatally
underlying causes of thrombocytopenia (Sola-Visner et al, acquired bacterial infection, particularly due to Group B
2009; Cremer et al, 2010), these are largely used in specialist streptococcus; and congenital viral infection, particularly due
laboratories and are unnecessary for most clinical problems. to cytomegalovirus (CMV) or occasionally Coxsackie virus.
Indeed, diagnosis and management of most cases can be NAIT is relatively uncommon as a cause of neonatal throm-
planned on the basis of the history, full blood count and blood bocytopenia in preterm neonates (Baer et al, 2009; Bussel &
film, together with serological investigations in selected cases Sola-Visner, 2009; Rastogi et al, 2011), mainly because of the
to identify NAIT. high prevalence of other causes. In the absence of a family
history of NAIT, we recommend screening preterm infants for
NAIT only after confirming a normal maternal platelet count
Preterm neonates
and excluding the more common causes of neonatal throm-
In preterm neonates, the majority of cases of thrombocytope- bocytopenia (Fig 1).
nia are due to conditions that cause placental ‘insufficiency’,
that is pregnancy-induced hypertension (PIH), including
Term neonates
preeclampsia and HELLP syndrome (haemolytic anaemia,
elevated liver enzymes, low platelet count), and/or fetal In contrast to preterm neonates, NAIT is the most important
intrauterine growth restriction (IUGR; ‘small for dates’) cause of thrombocytopenia in term neonates. In term neonates
(Murray & Roberts, 1996; Watts & Roberts, 1999; Kush et al, with thrombocytopenia who are otherwise well (Bussel & Sola-
2006). The haematological features and pattern of thrombo- Visner, 2009), and where there is no history to suggest
cytopenia are characteristic, proportional to the degree of PIH/ maternal idiopathic thrombocytopenic purpura, NAIT should

ª 2011 Blackwell Publishing Ltd, British Journal of Haematology, 156, 155–162 157
Review
be excluded by serological and genetic testing, as soon as
possible (see below), after excluding spurious thrombocyto-
penia.
A small proportion of term and preterm neonates (<1%)
will have persistent thrombocytopenia and it is these who
should have further specialized investigations performed
(Geddis, 2009; Rivers & Slayton, 2009). Some will have
diagnostic or suggestive dysmorphic features, such as neonates
with trisomy 21, 13 or 18 or Thrombocytopenia Absent Radii
(TAR) syndrome (Balduini et al, 2002, Israels et al, 2011). For
neonates with trisomy 21, 5–10% will have Transient Abnor-
mal Myelopoiesis (TAM), which can be identified by exam-
ination of the blood film that characteristically shows increased
circulating blasts, and is confirmed by the presence of a
mutation in the GATA1 gene (Brink, 2006; Webb et al, 2007;
Kanezaki et al, 2010).
Neonatal immune thrombocyopenia
Diagnostic approach to NAIT
Affected neonates present either with asymptomatic thrombo-
cytopenia, with minor bleeding (such as petechiae or purpura)
or with major bleeding. The most serious haemorrhagic
complication of NAIT is ICH, which is estimated to occur in
10–20% of untreated pregnancies and may present at any time
from 20 weeks gestation until a few days after birth (Mueller-
Eckhardt et al, 1989; Giovangrandi et al, 1990; Bussel et al,
2005; Ghevaert et al, 2007a; te Pas et al, 2007; Bussel &
Primiani, 2008). The most useful clinical pointer towards a
diagnosis of NAIT is unexplained severe thrombocytopenia
<50 · 109/l in the first 24–48 h of life in a term infant where
there is no evidence of the common causes of thrombocyto-
penia mentioned above. Usually there is no family history of
previously affected infants, as first pregnancies are often
affected and subsequent pregnancies in women with known
anti-human platelet antigen (HPA) antibodies are usually
monitored very closely in specialist fetal medicine units (Bussel
et al, 2005).
Given that NAIT results from transplacental passage of
maternal antibodies to fetal platelets expressing paternal HPAs
that the mother lacks, the diagnosis is made by demonstrating
platelet antigen incompatibility between mother and baby.
This is usually done serologically using MAIPA (monoclonal
antibody–specific immobilization of platelet antigens) assays to
detect maternal anti-HPA antibodies (Kiefel et al, 1987;
Campbell et al, 2007; Bessos et al, 2008; Killie et al, 2010).
Where possible, both parents and infant are also genotyped for
the most common HPA alloantigens (HPA-1a, -2, -3, -5b and -
15) (Dreyfus et al, 1997; Berry et al, 2000; Davoren et al, 2004;
Mandelbaum et al, 2005). Using these approaches, specific
HPA antibodies can be demonstrated in c. 20% of cases of
NAIT, of which c. 95% (in Caucasian populations) are due to
anti-HPA-1a or anti-HPA-5b, with the remaining 5% being
due to anti-HPA-2, -3 or -15 (Bonifacio et al, 2007; Ghevaert
158 ª 2011 Blackwell Publishing Ltd, British Journal of Haematology, 156, 155–162
et al, 2007a; Bussel & Primiani, 2008). Mothers with the
highest likelihood of developing antiplatelet antibodies among
Caucasians are those that are HPA-1a negative and HLA-
DRB*30101-positive (Symington & Paes, 2011). More difficult
are the 80% of cases with a clinical diagnosis of NAIT (severe,
otherwise unexplained, self-limiting neonatal thrombocytope-
nia) where no antibodies or maternal-neonatal platelet
incompatibility to these five HPA antigens is demonstrable.
Recent studies show that very few of these unexplained cases
are due to antibodies against minor HPA (such as HPA-6w
and HPA-9w) (Kaplan et al, 2005; Peterson et al, 2005;
Ghevaert et al, 2009). As a result, most groups feel that
routine screening for these very low frequency HPA antigens in
unexplained NAIT is very difficult to justify except in selected
severe cases and we advise that such cases are discussed on an
individual basis both with patients and with national platelet
reference centres.
Management of neonates with NAIT
In the majority of cases, thrombocytopenia resolves within a
week without long-term sequelae. In such cases therapy depends
on the clinical condition of the neonate and the platelet count.
All neonates with suspected NAIT should be screened for ICH by
cranial ultrasound because ICH in NAIT is associated with a very
high risk of severe neurodevelopmental problems, including
cerebral palsy (Ghevaert et al, 2007a). For well neonates with
documented or suspected NAIT who have no evidence of
haemorrhage, we advise prompt transfusion of HPA-1a- and
HPA-5b negative platelets where the platelet count
is < 30 · 109/l, in line with current British Committee for
Standards in Haematology (BCSH) guidelines; (Gibson et al,
2004) pending confirmation of the diagnosis. Where there is
evidence of ICH, or other major haemorrhage, we use a higher
threshold (50 · 109/l) to guide platelet transfusion (Gibson
et al, 2004). The platelet count should be maintained >50 · 109/
l at least until the end of the first week of life. In all cases, such
platelets should be CMV antigen-negative and single-donor
apheresis units; neonates who have received intrauterine platelet
transfusions should be given irradiated platelets (Davey, 1995;
Gibson et al, 2004; Ruhl et al, 2009). These are consensus
guidelines because neither a ‘safe’ platelet count nor an effective
platelet transfusion regimen has been identified yet (Bassler
et al, 2008) and practice continues to vary considerably between
different countries and individual centres (Bassler et al, 2008).
It is important to note that, in view of the poor outcome of
NAIT-associated ICH, transfusion should not be delayed if the
appropriate antigen-negative platelets are unobtainable (Allen
et al, 2004; Kiefel et al, 2006; Bussel & Primiani, 2008). Where
there is delay in obtaining HPA-compatible platelets, random
donor platelet transfusions or intravenous immunoglobulin
(IVIG) can be used as they often produce a significant platelet
increment in NAIT (Kiefel et al, 2006; Allen et al, 2007)
although the rise in platelet count after IVIG may be delayed
for at least 36 h (Mueller-Eckhardt et al, 1989; Bussel et al,

1997). The mechanism of action of IVIG in NAIT is not fully
understood but appears to involve inhibition of peripheral
immune platelet destruction both via changes to Fc receptors
on platelets and macrophage and Fc receptor-independent
mechanisms (Chen et al, 2010; Chow et al, 2010). It is
important to note that, as the platelet count in all neonates
falls over the first 4–7 d of life, all thrombocytopenic neonates
with NAIT should be monitored until there is a sustained rise
in their platelet count into the normal range (Roberts et al,
2008; Bussel & Sola-Visner, 2009). In some cases thrombocy-
topenia may persist for up to 8–12 weeks. In such cases, IVIG
usually provides a better alternative to repeated platelet
transfusions. Although this review focuses on management of
the neonate, it is important to remember that pregnant women
and mothers with HPA antibodies are at risk of post-
transfusion purpura, and so any blood products transfused
to the mother should be HPA-compatible.
Antenatal management of NAIT
Detailed discussion of the antenatal management of NAIT is
outside the scope of this review and is only briefly summarized
here (recently reviewed in (Mechoulan et al, 2011; Symington &
Paes, 2011; Vinograd & Bussel, 2010). All mothers of affected
neonates should be managed in subsequent pregnancies by fetal
medicine units experienced in NAIT. Management of women
with known HPA antibodies depends on the severity of
previously affected neonates with NAIT, the zygosity of the
father and on the HPA antibody specificity (Davoren et al, 2004;
Ghevaert et al, 2007b; Hayashi et al, 2010; Koh et al, 2010). The
antibody titre has also been shown to predict severity in several
recent studies (Killie et al, 2008; Skogen et al, 2009; Bertrand
et al, 2011) although the role of antibody titres in guiding
antenatal management remains to be determined. The most
effective antenatal management of pregnancies at risk of NAIT is
still unclear but most centres now rely mainly on risk-adapted,
non-invasive strategies (an expectant ‘wait and see’ approach, at
least in low risk cases, or administration of IVIG, with or
without steroids, to the mother) in view of the procedure-
associated risks of serial intrauterine platelet transfusions
(reviewed in (Symington & Paes, 2011; Vinograd & Bussel,
2010). Using this approach it is now clear that administration of
weekly IVIG to the mother, at least in a dose of 1 g/kg per week,
is not sufficient to treat high risk cases (i.e. where there has been
a previous child with ICH). For these cases, intermittent and
regular fetal umbilical vein sampling and transfusion of HPA-
compatible platelets in an experienced fetal medicine centre is
the mainstay of antenatal management (reviewed in Symington
& Paes, 2011; Vinograd & Bussel, 2010).
Diagnosis and management of neonatal autoimmune
thrombocytopenia
Almost all neonates with autoimmune thrombocytopenia are
identified as a result of screening women with known
ª 2011 Blackwell Publishing Ltd, British Journal of Haematology, 156, 155–162
Review
autoimmune disease. All neonates of mothers with autoim-
mune thrombocytopenia and/or systemic lupus erythematosus
should have their platelet count determined at birth, preferably
by a peripheral blood sample because artefactual thrombocy-
topenia due to clots from heel-prick samples or cord blood
samples are common. In neonates with normal platelet counts
(>150 · 109/l), no further action is necessary. In those with
thrombocytopenia, a platelet count should be repeated after
2–3 d as platelet counts are often at their lowest at this time
before rising spontaneously by day 7 in most cases (Burrows &
Kelton, 1990b). As in NAIT, thrombocytopenia may persist in
a small number of cases for up to 12 weeks (Burrows & Kelton,
1990b; Gill & Kelton, 2000). In this situation, where the
thrombocytopenia is severe (platelet count < 30 · 109/l in the
first week of life and <20 · 109/l thereafter), treatment with
IVIG 400 mg/kg per day given over 2–4 h for 5 d or 1 g/kg per
day for 2 d, total dose 2 g/kg), to which most babies promptly
respond, may be useful (Ballin et al, 1988).
Management of neonatal thrombocytopenia:
platelet transfusion
The only specific therapy for neonatal thrombocytopenia is
platelet transfusion. There are several national consensus
guidelines available (Del Vecchio et al, 2001; Garcia et al,
2001; Gibson et al, 2004; Allen et al, 2007), none of which are
based on randomized, controlled trials in neonates with severe
thrombocytopenia and there have been no trials to show
whether or not transfusion reduces haemorrhage or improves
outcome in neonates with severe thrombocytopenia (Baer
et al, 2009; Stanworth et al, 2009). Similarly, there is wide
variation in platelet transfusion thresholds in different units
worldwide and surveys have demonstrated numerous devia-
tions from hospital transfusion guidelines, highlighting the
widespread uncertainty about the most appropriate regimens
to treat and prevent severe haemorrhage in neonates (Joseph-
son et al, 2009; Stanworth et al, 2009). The only randomized
controlled trial of platelet transfusion in neonates was carried
out almost 20 years ago, aimed to raise the platelet count to
normal (>150 · 109/l) and was confined to neonates with
platelet counts above 50 · 109/l (Andrew et al, 1993).
We therefore use the current BCSH guidelines for platelet
transfusion in neonatal thrombocytopenia (Gibson et al, 2004)
with adjustments to define which neonates are at greatest
risk and may benefit from a higher transfusion threshold
(Table II). Our recent prospective study of neonates with
severe thrombocytopenia found that 91% of neonates whose
platelet counts fell below 20 · 109/l did not develop major
haemorrhage, suggesting that this is a reasonably safe threshold
for platelet transfusion for most neonates (Stanworth et al,
2009). Of those who did sustain a major haemorrhage in this
study, the vast majority were low birth weight with a
gestational age at birth of <28 weeks while the two term
neonates in the study had DIC, suggesting that a higher platelet
transfusion threshold may be necessary for these neonates
159
Review

Table II. Indications for neonatal platelet transfusion (Gibson et al,

2004). Concluding remarks

Platelet count Clinical indication

<20 · 109/l All neonates
<30 · 109/l <1 kg and <1 week age
Clinically unstable (fluctuating BP)
Previous major bleeding (Grade 3–4 IVH)
Current minor bleeding: petechiae,
puncture site oozing, blood-stained ET secretions
Coagulopathy
Requiring surgery or exchange transfusions
<50 · 109/l Major haemorrhage
IVH, intraventricular haemorrhage; ET, endotracheal tube; BP, blood
pressure.
(Stanworth et al, 2009). Interestingly, no relationship was
found between the platelet count and the occurrence of major
haemorrhage (Stanworth et al, 2009). Nevertheless, many
consensus guidelines (Del Vecchio et al, 2001; Garcia et al,
2001), including our own and the BCSH guidelines (Gibson
et al, 2004), recommend a threshold platelet count of
50 · 109/l for neonates with major haemorrhage. Although
this seems intuitively reasonable, as this group of patients has
one of the highest incidences of intracranial haemorrhage with
attendant risks of long-term disability (Lemons et al, 2001),
there is as yet no direct evidence that administering platelet
transfusions at this threshold is either necessary or beneficial.
Given that a very high proportion of thrombocytopenic
neonates receive platelet transfusions (69% in our recent
study) (Stanworth et al, 2009) and repeated transfusions are
often given (Strauss, 2008, 2010; Josephson et al, 2009), the
data from these studies is now being used to design a
randomized controlled trial of platelet transfusion for neonates
with different degrees of neonatal thrombocytopenia following
similar principles to those used for adults with severe
thrombocytopenia (Stanworth et al, 2010).
Thrombocytopenia is a very common finding in the neonatal
unit. The incidence of thrombocytopenia is inversely propor-
tional to gestational age and birth weight. Early onset
thrombocytopenia in a preterm neonate is generally secondary
to placental insufficiency and usually resolves in 10–14 d. In
preterm neonates with severe thrombocytopenia, congenital
and perinatal infections should be excluded when there is no
evidence of placental insufficiency. Late onset thrombocyto-
penia occurs most commonly due to sepsis and or necrotizing
enterocolitis. In term babies with severe thrombocytopenia
who are otherwise well, NAIT should be excluded and prompt
treatment with HPA-negative platelets should be instituted.
There is a wide variation in transfusion triggers and transfu-
sion practice among neonatal units and the vast majority of
neonates are given prophylactic platelet transfusions in the
absence of significant bleeding, despite the fact that no data
exist to demonstrate the benefit in maintaining high platelet
counts in preterm neonates for prevention of major haemor-
rhage.
Acknowledgements
We acknowledge the invaluable support of the staff at the
Diagnostic Haematology Laboratory at Hammersmith Hospi-
tal, Imperial College Healthcare NHS Trust, who ensure the
production of high quality blood films on all neonates
admitted to the neonatal intensive care unit and, in particular,
Corrine Jury, who died recently, and to whose memory we
dedicate this paper. We also acknowledge David Roper for his
help with the photomicrographs. IR is funded in part by the
Imperial College London Comprehensive Biomedical Research
Centre, which receives funding from the Biomedical Research
Centre funding scheme administered by the National Institute
of Health Research (Department of Health).

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