NEONATAL

THROMBOCYTOPENIA
INTRODUCTION
Thrombocytopenia in neonates is traditionally defined as a platelet count
of less than 1.5 LAKH/cmm
Classified as mild 1-1.5 lakh/cmm , moderate (50,000-1lakh/cmm), or
severe (<50,000/cmm).
Overall incidence of neonatal thrombocytopenia is relatively low (0.7%-
0.9%)
Incidence more in NICU setups approx. 25% , preterm > term babies ,
incidence inversely correlated to the gestational age, approximately 70%
among ELBW
 Most Common Aetiology Less Common Aetiology
FETAL Alloimmune (NAIT) Severe rhesus disease
Congenital infection Congenital/inherited (e.g. Wiskott-Aldrich
Aneuploidy syndrome)
Autoimmune (e.g. ITP, SLE)

EARLY ONSET NEONATAL Placental insufficiency Congenital infection

Perinatal asphyxia Thrombosis (e.g. aortic, renal vein)
DIC Metabolic disease (e.g. propionic and
Alloimmune (NAIT) methylmalonic acidaemia)
Autoimmune Congenital/inherited e.g.Kasabach-Merritt
Congenital TAR
Congenital Amegakaryocytic
Thrombocytopenia (CAMT)

LATE ONSET NEONATAL Late-onset sepsis Congenital infection (e.g. CMV, toxoplasma,
NEC rubella)
Autoimmune
Kasabach-Merritt Phenomenon
Metabolic disease (e.g. propionic and
methylmalonic acidaemia)
Congenital/inherited (eg TAR, CAMT)
WORKUP
PRESENTATION
May be asymptomatic or present with bruises , petechiae , purpura to
catastrophic intracranial haemorrhage and death
Features of sepsis and DIC , frank bleeding
Previously affected sibling , Recurrent fetal loss and stillbirth, Antenatal
ICH/hydrocephalus NAIT
INVESTIGATIONS if platelets persistently < 1lakh/cmm
Repeat CBC assess trends in Hb and TLC, platelet count stable or declining
PBS , SEPSIS Screen , Coagulation profile , DIC workup , congenital infection
screen , maternal platelet counts
 APPROACH TO THE
THROMBOCYTOPENIC NEONATE
2 things to consider age at onset ( early <72 hrs vs late > 72 hrs ) and
clinical condition of the baby ( well vs ill )
Infection and sepsis should always be kept in mind regardless of the time
of presentation and the infant's appearance
Most frequent cause of early onset thrombocytopenia in a well-appearing
neonate is placental insufficiency ( PIH,IUGR,DM) , always mild to
moderate, presents shortly after birth, and resolves within 7 to 10 days
Severe early-onset thrombocytopenia in a Well infant immune-
mediated thrombocytopenia high risk of bleeding
 In any case if PC improving , no further evaluation required
In a well infant if Platelet count not rising by 10days / in a ill infant if
thrombocytopenia persists without evidence of sepsis or DIC consider
1.TAR 2.Proximal radio-ulnar synostosis
3.Trisomy 13, 18, or 21, Turners/Noonan syndrome 4. TORCH Infections
5.Viral infections (HIV,enterovirus) 6. Chromosomal abnormalities
7.IEMs 8. Thrombosis
9.Congenital thrombocytopenias
Late-onset thrombocytopenia
Presumed to be due to sepsis (bacterial or fungal) or necrotizing
enterocolitis (NEC) unless proven otherwise
Appropriate treatment with antibiotics, fluid resuscitation, and bowel
rest usually improves the platelet count in 1 to 2 weeks
Viral infections such as herpes simplex virus, CMV, or enterovirus
should also be considered
Drug-induced thrombocytopenia heparin, antibiotics (penicillins,
ciprofloxacin, cephalosporins, metronidazole, vancomycin, and
rifampin), indomethacin, famotidine, cimetidine, phenobarbital, or
phenytoin
 IMMUNE THROMBOCYTOPENIA

Passive transfer of antibodies from the maternal to the fetal circulation

and destruction of platelets
1. Neonatal alloimmune thrombocytopenia (NAIT) - antibody is produced
in the mother against a specific human platelet antigen (HPA) present in
the fetus but absent in the mother. The antigen is inherited from the
father
2. Autoimmune thrombocytopenia antibody is directed against an
antigen on the mother's own platdets (autoantibody) as well as on the
baby's platelets
NAIT
Severe thrombocytopenia at birth or shortly after , in the absence of other risk
factors
In contrast to rhesus haemolytic disease, platelet allo-immunization can occur
during the first pregnancy
Unexpected bruising and purpura or severe intracranial haemorrhage , ICH ~20%
death in 10% and neurological sequelae in 20% of these newborns
Combination of severe neonatal thrombocytopenia with a parenchymal ICH
highly suggestive of NAIT , along with previous affected sibling
Possibility of allo-immunization is particularly high for HPA1a, 5b and 15b
among Europeans, for HPA2b and HPA3a among Maori, for HPA 4b among
Asians, and for HPA6b among Polynesians
 Laboratory Investigation - When NAIT is suspected, maternal and
paternal blood should be submitted for confirmatory testing ( 90% -
antigen HPA 1, 3, and 5 , if negative then HPA 9,15 and 4 (Asian)
Neonatal serum may be screened for the presence of anti-platelet
antibodies
Brain imaging studies should be performed as soon as NAIT is
suspected, regardless of neurologic manifestations will dictate the
aggressiveness of the treatment for the affected infant and for
mother's future pregnancies
 Management: :
1. Suspected NAIT in an unknown pregnancy RDP transfusions is considered
the first line of therapy
Clinically stable and no evidence of ICH , platelets given when the platelet
count is less than 30,000/cmm
PC to be kept above 1,00,000/cmm in case of ICH
Additionally IVIG @ 1 g/kg/day X 2 days to increase the patient's own platelets
and potentially to protect the transfused platelets
Those who fail to respond to random-donor platelets and IVIG , blood banks
should be alerted to arrange for antigen-negative platelets (either from HPA-
1b1b and 5a5a donors, compatible in >90% of cases )
Methylprednisolone (1 mg/kg bid for 3-5 days) has also been tried
 2. MANAGEMENT OF THE NEONATE WITH KNOWN NAIT if baby
thrombocytopenic , transfusion of genotypically matched platelets e.g
HPA-1b1b platelets is first line therapy
3. ANTENATAL MANAGEMENT OF PREGNANT WOMEN WITH PREVIOUS
HISTORY of NAIT followed up in high-risk obstetric clinics during all
future pregnancies , maternal treatment with IVIG (1-2 g/kg/wk) +
steroids, starting at 12 or at 20 to 26 weeks' gestation
Intensity of prenatal treatment based on the severity of the
thrombocytopenia and the presence or absence of ICH in previous
affected fetus
Autoimmune thrombocytopenia
Early-onset thrombocytopenia and a maternal history of ITP or
autoimmune disease
Study shows 25% of neonates born to ITP mothers exhibited
thrombocytopenia at birth; 9% being severe and 15% requiring treatment
All neonates born to mothers with autoimmune diseases should have a
screening platelet count at or shortly after birth , if normal no further
evaluation
If the infant has mild thrombocytopenia, the platelet count should be
repeated in 2 to 3 days, usually reaches the nadir between days 2 and 5
after birth.
 If the platelet count is < 30,000/cmm, IVIG (1 g/kg, repeated if
necessary) is the first line of therapy. RDP, in addition to IVIG, should
be provided only if the infant has evidence of active bleeding
Cranial imaging should be obtained in all infants with platelet counts
<50,000/cmm to evaluate for intracranial haemorrhage
Maternal management - treatment of ITP during pregnancy is mostly
based on the risk of maternal haemorrhage , antenatal steroids/IVIG
dont raise neonatal platelet counts
No evidence of cesarean section being safer for the fetus
Congenital Thrombocytopenic
Syndromes
Congenital amegakaryocytic thrombocytopenia (CAMT) usually manifests
within the 1st few days to week of life
AR , Mutation in the stem cell TPO receptor
Bone marrow shows an absence of megakaryocytes , progress to marrow
failure over time
HSCT is curative
TAR syndrome consists of thrombocytopenia (absence or hypoplasia of
megakaryocytes) and radial deformities
Intolerance to cows milk formula (present in 50%)
The thrombocytopenia of TAR syndrome frequently remits over the 1st
few yrs of life.
 Amegakaryocytic thrombocytopenia with radioulnar synostosis
Caused by a mutation in the HOXA11 gene.
Different from TAR syndrome, marrow aplasia +ve
WAS is characterized by thrombocytopenia, with small platelets, eczema,
and recurrent infection as a consequence of immune deficiency
Successful HSCT cures WAS
MYH9-related thrombocytopenia AD macrothrombocytopenia, neutrophil
inclusion bodies, with sensorineural deafness/renal disease/eye disease
Mild to moderate thrombocytopenia with giant platelets
TAKE HOME MESSAGES :
Consider clinical risk factors in addition to absolute platelet count:
Timing of onset (early versus late)
Primary origin (maternal, placental or neonatal/fetal)
Individual risk for bleeding (gestational age, postnatal age, NEC/sepsis,
surgery, signs of bleeding).
Persistent unexplained thrombocytopenia should be investigated for
uncommon causes.
Platelet transfusion to be done as per standard guidelines
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