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Petechial rash in neonates: Management algorithm

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 Journal of Neonatology Vol. 22, No. 1, Jan. - Mar. 2008

REVIEW ARTICLE

Petechial rash in neonates: Management algorithm

Dinesh Yadav, Jagdish Chandra
Department of Pediatrics, Lady Hardinge Medical College, & Kalawati Saran Children’s Hospital, New Delhi 110 001
jchandra55@yahoo.co.in

Abstract Wiskott-Aldrich syndrome

Chediak-Higashi syndrome
Petechial rash in neonatal period commonly results from May-Hegglin anomaly
thrombocytopenia. Disorders of coagulation and those Alport syndrome
affecting vascular integrity may cause purpuric rash. Bernard-Soulier syndrome
Common causes of neonatal thrombocytopenia include early Marrow Infiltrative disorders
onset thrombocytopenia (onset < 72 hours) due to placental Congenital leukaemia
insufficiency, perinatal asphyxia, perinatal infections and DIC. Congenital neuroblastoma
Alloimmune thrombocytopenia is rare but potentially serious Letterer-Siwe disease
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Osteopetrosis
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disorder. Late onset thrombocytopenia (onset > 72 hours)

almost always results from sepsis and NEC. Intrauterine b) Increased platelet destruction
infections and perinatally acquired dengue and Intravascular coagulation
Disseminated (DIC associated with systemic infection
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chikungunaya infections also need to be considered in

appropriate clinical settings. or severe birth asphyxia)
Infantile acute hemorrhagic edema, meningococcal rash Localized (renal vein thrombosis, necrotizing
and blue berry muffin baby are causes of purpuric rash entrocolitis, maternal eclampsia, Kasabach-Merritt
without thrombocytopenia and may require exclusion. syndrome)
In addition to these, this review also includes uncommon Systemic Infection (bacterial, viral, fungal,
causes of petechial/ purpuric rash in neonatal period. Clinical protozoal)
approach to diagnosis and management are discussed. Acquired
Congenital
Immune mediated
Neonatal alloimmune thrombocytopenia
Introduction
Neonatal autoimmune thrombocytopenia
von Willebrand disease (type IIB)
Petechial or purpuric rashes are commonly observed in
c) Combination of decreased production and
the neonatal period, particularly in sick premature neonates.
increased destruction
It can be an isolated observation or may be associated with
Infection (congenital- TORCH or acquired- bacterial
systemic bleeding manifestations. Such rashes commonly
sepsis)
occur due to platelet disorders. However, coagulation
Erythroblastosis fetalis
disorders or diseases affecting vascular integrity (vasculitis,
d) Miscellaneous
infections) can also cause similar lesions.
Exchange transfusion
Extracorporeal membrane oxygenation
Polycythemia
Etiopathogenesis 2. Coagulation disorders
A. Inherited coagulation factor deficiencies
1. Platelet Disorders- Both quantitative and qualitative X-linked recessive (Hemophilia A, B)
defects in platelets can be associated with bleeding Autosomal dominant (von Willebrand disease)
manifestations including petechial/ purpuric rashes - Autosomal recessive (Defects of Factor XI, VII, V, X, II,
A. Qualitative disorders- Glanzman thrombasthenia, XIII and fibrinogen)
Bernard-Soulier syndrome, platelet type vWD, storage B. Acquired coagulation factor deficiencies
pool defects. Vit K deficiency
B. Quantitative disorders- Neonatal thrombocytopenia Sepsis/ necrotizing entrocolitis
can be due to Renal vein thrombosis (RVT)
a) Decreased platelet production- Significant liver disease
Congenital thrombocytopenias Maternal drug intake (phenytoin, phenobarbitone,
Amegakaryocytic thrombocytopenia salicylates and coumadin compounds.
Thrombocytopenia- absent radii (TAR) syndrome 3. Combined Platelet and Coagulation disorders
Amegakaryocytic thrombocytopenia without limb A. Disseminated intravascular coagulation
anomalies

19
 Journal of Neonatology Vol. 22, No. 1, Jan. - Mar. 2008

B. Hepatic dysfunction platelet count less than 150x109/L is the accepted definition
4. Disorders of vessels for neonatal thrombocytopenia. Thrombocytopenia in
Hemangiomas neonates is classified as mild (platelet count 100-150x109/
Vascular malformation L), moderate (platelet count 50-100x109/L) and severe
Infantile acute hemorrhagic edema (platelet count <50x109/L) 4.
The reported overall incidence of neonatal
thrombocytopenia ranges from 0.7% to 4% and severe
Clinical features thrombocytopenia occurs in 0.1-0.5% neonates.
Thrombocytopenia is more common in NICU, seen in 22-
Petechiae in neonate are not always pathological. 35% of all babies admitted in NICU and in upto 50% of those
Petechiae may occur in areas experiencing trauma during admitted to NICU requiring intensive care and approximately
delivery, such as the face, in a delivery where the face is the 20% of these episodes of thrombocytopenia are severe1.
presenting part; however, neonates with diffuse petechiae Premature or sick newborns are more likely to have
should be evaluated for thrombocytopenia. Many neonates thrombocytopenia.
have erythema toxicum, a benign rash with an erythematous Increased platelet consumption has been considered the
base and a white or yellow papule. This rash, which usually principal mechanism for neonatal thrombocytopenia but
appears 24 hours after birth, is scattered over the body and some of the recent studies have reported that impaired
can last for up to 2 weeks. platelet production is the major mechanism accounting for
upto 75% of cases with early onset neonatal
Thrombocytopenia thrombocytopenia 2,3. Based on onset, neonatal
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Petechial bleeds are most commonly seen in association thrombocytopenia can be classified into 3 major groups as
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with thrombocytopenia, while coagulation disorders usually shown in Table 1.

present with echymoses and mucosal bleeding. Platelet Fetal thrombocytopenia is identified during diagnostic
counts in newborn are similar to adult value ranging between investigations for inherited thrombocytopenias, alloimmune
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150 and 450 x 109/L, with mean platelet volume of 7 to 9 fl. thrombocytopenia in fetus with intracranial hemorrhage,
Cordocentesis studies reveal a mean platelet count of 187 during ultrasonographic assessment of fetus with hydrops
x109/L at 15 weeks of gestation, rising to normal adult values or hemolytic disease or malformations associated with
for both term and preterm infants at birth2, therefore, a congenital infections.

Table 1: Classification of fetal and neonatal thrombocytopenia2

Conditions
Fetal thrombocytopenia • Alloimmune thrombocytopenia
• Congenital infection (e.g. CMV, toxoplasma, rubella, HIV)
• Aneuploidy (e.g. trisomies 18, 13, 21)
• Autoimmune (e.g. ITP, SLE)
• Severe Rh hemolytic disease
• Congenital/inherited (e.g. Wiskott-Aldrich syndrome)
Early onset neonatal
thrombocytopenia (<72 hours) • Placental insufficiency (e.g. Pre-eclampsia, IUGR, diabetes)
• Perinatal asphyxia
• Perinatal infection (e.g. E coli, Group B Streptococci, H.influenzae)
• DIC
• Alloimmune
• Autoimmune (e.g. maternal ITP, SLE)
• Congenital infection (e.g. CMV, toxoplasma, rubella, HIV)
• Thrombosis (e.g. aortic, renal vein)
• Bone marrow replacement (e.g. congenital leukaemia)
• Kasabach-Merritt syndrome
• Metabolic disease (e.g. proprionic and methylmalonic acidaemia)
• Congenital/inherited syndromes (e.g. Thrombocytopenia with
absent radii (TAR), Congenital amegakaryocytic
thrombocytopenia (CAMT)
Late onset neonatal thrombocytopenia • Late onset sepsis
(>72 hours) • NEC
• Congenital infection (e.g. CMV, toxoplasma, rubella, HIV)
• Autoimmune
• Kasabach-Merritt syndrome
• Metabolic disease (e.g. proprionic and methylmalonic acidaemia)
• Congenital/inherited (e.g. TAR, CAMT)

20
 Journal of Neonatology
Early onset thrombocytopenia is usually seen in preterm
neonates because of placental insufficiency and fetal
hypoxia e.g. maternal pre-eclampsia and fetal intrauterine
growth retardation. This thrombocytopenia has a remarkably
consistent pattern, with a platelet nadir around day 4 and
resolution by day 10. Thrombocytopenia is usually mild to
moderate, resolves spontaneously and usually does not
require specific therapy. Severe early thrombocytopenia is
unusual and occurs in association with severe perinatal
infections or following perinatal asphyxia. In both situations,
DIC is often a significant contributor.
Late onset thrombocytopenia is almost exclusively caused
by late onset sepsis or necrotizing enterocolitis. Platelet
counts fall rapidly in 24-48 hours after onset and severe
thrombocytopenia is more common, prolonged and often
requires platelet transfusion2.
Neonatal alloimmune thrombocytopenia (Nait)
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NAIT is similar to hemolytic disease of newborn, caused
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by maternal IgG alloantibodies that cross the placenta into
the fetal circulation and accelerate removal of platelets from
the circulation. Unlike hemolytic disease of newborn, NAIT
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may occur in the first pregnancy. Mothers of infants with
NAIT have normal platelet counts and no bleeding history.
Most frequently implicated alloantigens are HPA-1a and HPA-
5b, which are responsible for 80% and 15% of the cases
respectively. Woman possessing HLA DR3 and HLA DRw6
have higher risk of forming these alloantibodies.
Clinical presentation of NAIT is severe isolated
thrombocytopenia in a healthy, full term infant. Minor
bleeding in the form of petechiae, gastrointestinal
hemorrhage or hematuria is a frequent finding. Fifteen to
20% of these babies may have intracranial hemorrhage, half
of which occurs in intrauterine life. Severe bleeding in NAIT
is due to severe thrombocytopenia and platelet dysfunction
caused by antiplatelet alloantibody impairing aggregation
through binding to Gp IIb/IIIa. Other complications observed
include anemia and jaundice2.
Diagnosis is based on clinical presentation and presence
of severe thrombocytopenia and confirmed by serologic and/
or DNA testing. Serologic testing includes typing of the
parents’ platelet antigens and testing for presence of
antiplatelet alloantibody in maternal serum. DNA based
platelet typing helps in determining paternal zygosity for
the implicated alloantigen, which is helpful in predicting
the risk of recurrence in future pegnancies2,4.
Neonatal autoimmune thrombocytopenia
Newborns with maternal autoimmune disorders may
present with thrombocytopenia with a milder clinical course
than NAIT. Usually mother has idiopathic thrombocytopenic
purpura (ITP), but other autoimmune disorders like SLE,
lymphoproliferative disorders and hyperthyroidism can also
present with neonatal autoimmune thrombocytopenia. The
overall incidence of thrombocytopenia in the offspring of
mothers with ITP is approximately 15 to 45%, while severe
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Vol. 22, No. 1, Jan. - Mar. 2008
thrombocytopenia is seen in 5-15% newborns. Risk of ICH is
much less in these neonates compared with NAIT4.
Congenital/Neonatal Infections
Intrauterine infections (TORCH group) are other common
causes of neonatal thrombocytopenia. These babies usually
present with hepatosplenomegaly, intrauterine growth
retardation, thrombocytopenia and petechial rash. Among
TORCH group of infections, cytomegalovirus is most
common cause of intrauterine infection. The fetus may
become infected if a woman has a primary infection during
pregnancy or if she has reactivation of a latent infection that
was acquired before pregnancy. About 15% of infants born
to women with primary infection have clinical disease that
ranges from mild to severe. Toxoplasmosis can also present
with similar clinical features, although it is much less
common and usually associated with maculopapular rash.
Chorioretinitis is more common in association with
toxoplasmosis. Congenital rubella infection is usually
associated with purpuric rash, cataracts and congenital heart
disease5.
Vertically transmitted HIV infection is usually
asymptomatic at birth, although rare newborn with
congenital HIV infection may present with intrauterine
growth retardation, hepatosplenomegaly, pancytopenia,
diffuse leukoencephalopathy, and early-onset Pneumocystis
carinii infection5.
Sepsis is a very common cause of neonatal
thrombocytopenia. Approximately 60 % neonates with
proven sepsis have been found to have thrombocytopenia
of varying severity. Conversely, thrombocytopenia appearing
or worsening after 72 hours of age has been found to result
almost exclusively from sepsis or NEC. Fungal and gram
negative pathogens have been found to be have more severe
and prolonged thrombocytopenia compared with gram
positive organisms. The mechanisms involved include
increased destruction, decreased production or DIC 4,6,7.
In tropical countries, vertical transmission of dengue virus
has been reported in neonates born to mothers having acute
dengue virus infection 4-8 days prior to delivery. The neonates
developed acute febrile illness, respiratory distress,
mucocutaneous bleeding and multiorgan failure8,9. Similarly
mother to child transmission of chikungunya virus has been
reported during massive outbreak in Reunion Island in 2005-
2006. In most of the instances, mothers experienced illness
within 5 days of delivery while neonates presented at 3-7
days with fever, rash, peripheral edema, thrombocytopenia,
lymphopenia, seizures and hemorrhagic syndrome10. Similar
cases have been reported in Indian literature11.
Neonatal Thrombocytopenia- Miscellaneous
causes
Newborn should be examined for skeletal defects and
dysmorphic facies, which are pointers to inherited causes of
thrombocytopenia. Thrombocytopenia- absent radii
syndrome can present with petechial bleeds in newborn.
 Journal of Neonatology
Thrombocytopenia is worse in neonatal period and improves
later in infancy 2.Fanconi’s anemia, Wiskott–Aldrich
syndrome and several metabolic diseases, may also manifest
as neonatal thrombocytopenia.
Kasabach-Merritt Syndrome is the association between
thrombocytopenia and giant hemangioma of infancy. It is
not associated with the common infantile capillary or
cavernous hemangioma, seen in 5 to 10% of children. Rather,
Kasabach-Merritt Syndrome appears to be a complication of
two rare, aggressive kaposiform hemangioendothelioma
and the tufted hemangioma. Most patients present in the
first few weeks of life. The vascular lesions are usually solitary
and involves the extremities, neck and trunk. These
hemangiomas grow rapidly for initial several months,
followed by spontaneous regression. Probable pathogenesis
for thrombocytopenia is due to platelets being trapped in
abnormal endothelium of hemangioma. Besides
thrombocytopenia, there are schistocytes on peripheral
smear (suggesting microangiopathic anemia) and laboratory
evidence of DIC, including hypofibrinogenemia and elevated
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levels of fibrin degradation products12-14.
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Congenital leukaemia is another rare but important cause
of neonatal thrombocytopenia, particularly in a sick newborn
in association with hepatosplenomegaly, lymphadenopathy
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and leukocytosis. Similarly juvenile chronic myelogenous
leukaemia has been reported in a newborn presenting with
petechial rash, splenohepatomegaly and lymphadenopathy6.
Various bone marrow infiltration disorders can present
with pancytopenia and petechial rash in newborn period.
These disorders include familial hemophagocytic syndromes,
hemophagocytic syndrome associated with Epstein Barr virus
and Letterer-Siwe disease, the most aggressive form of
Langerhans’-cell histiocytosis15.
Non-thrombocytopenic causes of neonatal
petechial rash
A) Coagulation disorders- both inherited and acquired
coagulation disorders can present with diffuse bleeding
manifestation. Children with inherited coagulation factor
deficiencies (Hemophilia A, B and other factor
deficiencies) may have family history of bleeding disorder.
Recent studies indicate that 40 to 70% of children with
severe hemophilia are diagnosed in the neonatal period
and vast majority present with bleeding symptoms
including bleeding from umbilical stump, large
cephalhematoma, subgaleal and intracranial hemorrhage
following uncomplicated childbirth or following
venipuncture, heel prick or circumcision. Bleeding in
subcuatenous tissues and muscles is associated with
purpuric skin lesions4,16.
Among acquired causes of clotting factor deficiencies,
vitamin K deficiency is most common. Vitamin K
deficiency bleed (VKDB) can be classified in three patterns
based on timing of presentation as early, classic and late.
Early form of VKDB manifests within 24 hours of birth
and usually associated with maternal use of specific
medications which interfere with vitamin K store or
function. These include anticonvulsants (carbamazepine,
22
Vol. 22, No. 1, Jan. - Mar. 2008
phenytoin, phenobarbitone), antibiotics (cephalosporins),
antitubercular drugs (rifampicin, isoniazid) and vitamin K
antagonists (coumadin compounds).
Classic form of VKDB manifests on day 2 to 7 of life in
healthy, full term infants. Etiologic factors include poor
placental transfer of vitamin K, marginal content of
vitamin K in breastmilk, delayed or inadequate feeding,
malabsorption and a sterile gut.
Late form of VKDB manifests after 7days of life. It is seen
in exclusively breastfed babies and in babies with
hepatobiliary diseases (secondary form)4.
VKDB can present as minor skin or mucosal bleeds,
bleeding from injection site or cuts, subcutaneous
hematoma formation, gastrointestinal bleeding or
following surgical intervention. Severe life threatening
intracranial bleeding is relatively more common in late
onset VKDB17.
B) Disseminated intravascular coagulation (DIC) is
another important cause of bleeding in newborn. It is a
secondary process with common etiologic factors being
birth asphyxia, shock, infection, respiratory distress
syndrome, necrotizing enterocolitis and meconium
aspiration syndrome.
DIC usually occurs in sick infants, more in premature
neonates. Common bleeding manifestations include skin
bleeds, oozing from mucus membranes or sites of invasive
procedures, hematuria, pulmonary hemorrhage and rarely
ICH4.
C) Liver disease associated coagulopathy of newborn is
similar to those in adults and reflects failure of hepatic
synthetic functions superimposed on physiologic
immaturity, activation of coagulation and fibrinolytic
systems, loss of hemostatic proteins into ascetic fluid and
splenic sequestration of platelets. Some of the common
pathologic causes of hepatic dysfunction in newborn are
viral hepatitis, hypoxia, total parenteral nutrition, biliary
atresia, inherited metabolic disorders and fetal hydrops.
Symptoms include petechiae, ecchymosis, mucous
membrane bleeding, hemorrhage from gastrointestinal
varices or into the abdomen and rarely ICH. Laboratory
abnormalities include prolongation of PT,PT T,
thrombocytopenia and prolonged bleeding time. Plasma
levels of factor V, VII, fibrinogen, AT and plasminogen are
decreased; fibrin degradation products and D-dimer are
increased. Normal levels of factor VIII, reflecting significant
extrahepatic synthesis, can help to distinguish severe liver
disease from DIC. Etiology of thrombocytopenia and
platelet dysfunction includes impaired platelet
production, inappropriate platelet activation and
degranulation, splenic sequestration and accelerated
clearance4.
D) Disorders mimicking purpura: Certain other disorders
may need to be differentiated from skin bleeds. Infantile
acute hemorrhagic edema ia a rare cause of neonatal
petechial rash. It is a leukoclastic vasculitis, confined to
the skin without visceral involvement. It is characterized
by inflammatory edema and ecchymotic purpura in a
target pattern. Histology of the skin shows typical
leukoclastic vasculitis and the condition has therefore
been considered a variant of Henoch-Schonlein purpura.
Most affected infants have dramatic onset, short benign
 Journal of Neonatology
course and spontaneous resolution within several weeks18-
20
. Meningococemia has been described to occur in
neonatal period presumably due to transplacental passage.
This infection should be considered in neonates with sepsis
and purpuric rash particularly during epidemics 21,22.
Blueberry muffin baby is a descriptive term for dark
bluish purpuric nodules reflective of extramedullary
hematopoeisis. These lesions most commonly result from
intrauterine infections, such as rubella and
cytomegalovirus, and less commonly with malignancy,
hematologic disorders and Langerhans cell
histiocytosis23,24
Infants with congenital protein C deficiency can present
in the neonatal period with either purpura fulminans or
massive thrombosis16.
Approach and diagnostic investigations
Every newborn presenting with petechial and purpuric
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rash should be evaluated by a detailed history along with
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complete physical examination and supported by
appropriate investigations.
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History
♦ Onset – since birth in a healthy newborn localized to
presenting part may be normal, while generalized petechial
rash at birth may be manifestation of NAIT, autoimmune
thrombocytopenia, inherited thrombocytopenias or early
onset vitamin K deficiency. Similarly, later onset may be
associated with sepsis associated thrombocytopenia or
coagulation disorders.
♦ Duration and progression of rash.
♦ Associated other mucocutaneous bleeding manifestations
and history suggestive of ICH
♦ History pertaining to general condition of neonate- healthy
or sick newborn
♦ Antenatal history- intrauterine infections, IUGR, drug
intake, radiation exposure.
♦ Perinatal history- eclampsia, preeclampsia, infections,
antepartum bleeding
♦ Neonatal history- gestational age, birth asphyxia, birth
trauma, difficult delivery, hydrops, administration of
vitamin K at birth
♦ Maternal history- bleeding disorders, autoimmune diseases
(ITP, SLE, hyperthyroidism, diabetes etc),acute febrile illness
including dengue, chikungunya and meningococcemia.
♦ Family history- bleeding disorders, neonatal deaths,
cytopenias, skeletal anomalies and thrombocytopenia in
a previous infant.
Examination
♦ General condition of the neonate- healthy/ sick, signs of
sepsis
♦ Gestation –premature/ mature
♦ Bleeding manifestations- localized versus generalized
bleeding. petechiae, purpura, ecchymosis, bleeding at
venepuncture sites, mucosal bleeds, blanching rash
suggesting vasculitis, skin necrosis suggesting protein C
deficiency / purpura fulminans or meningococcemia, signs
23
Vol. 22, No. 1, Jan. - Mar. 2008
of ICH (full bulging anterior fontanelle, irritability/depressed
sensorium, seizures, focal neurological deficits)
♦ Skeletal anomalies- microcephaly, limb anomalies (TAR),
other skeletal anomalies
♦ Congenital malformation- abnormal facies (intrauterine
infections), hemangioma, congenital heart disease,
cataract.
♦ Hepatosplenomegaly/ lymphadenopathy- intrauterine
infections, congenital leukemias, hemophagocytic
syndromes, hepatobiliary disease.
♦ Signs of DIC, NEC, hepatic failure
Investigations
Primary investigations in evaluation of cases with bleeding
manifestations include:
• Complete blood counts including platelet count and
peripheral blood smear examination. Assessment should
be made for presence of other cytopenias (bi/
pancytopenia). Platelet size and morphology should be
noted on smear examination (micro platelets suggesting
Wiskott-Aldrich syndrome, large platelets suggesting
Bernard- Soulier syndrome).
• Prothrombin time (PT) and Activated Partial
Thromboplastin time (aPTT).
Bleeding time ( BT) is usually not included in the screening
process as the routinely available test is imprecise and not
very reliable. As a substitute, PFA-100 platelet function
screen has been introduced but it has not yet become
easily available.
Other investigations are done based on clinical history
and examination findings-
♦ Mother’s platelet counts- healthy newborn with
thrombocytopenia, history of recurrent neonatal deaths,
cytopenias, skeletal anomalies and thrombocytopenia in
previous infant- to diagnose alloimmune or autoimmune
thrombocytopenias.
♦ Fibrin degradation products, D-dimer assay- DIC
♦ Specific factor assays- clotting factor deficiencies
♦ Serologic and/or DNA testing in suspected NAIT for
alloantigens
♦ Liver function tests- hepatic diseases
♦ TORCH, VDRL, HIV- vertical transmission of infections
♦ Blood and other relevant cultures for sepsis and
meningococcemia
♦ Serological tests and DNA/RNA PCR for dengue and
chikungunya infection
♦ Bone marrow examination- congenital leukemia, storage
disorders, hemophagocytic disorders.
Besides above investigations, some of the studies have
utilized thrombopoietin (Tpo), reticulated platelets, plasma
glycocalicin levels and megakaryocyte culture to differentiate
between hypoplastic and hyperdestructive causes of
idiopathic thrombocytopenia25-27. These tests are not routinely
available. Fortunately they are required for evaluation of
persistent thrombocytopenia when the cause is not readily
identified.
Based on the results of these screening tests, the patients
with bleeding manifestations can be grouped as follows:
• A-Cases with abnormally low platelet count with normal
PT and aPTT
 Journal of Neonatology
• B-Cases with abnormally low platelet count and abnormal
PT and aPTT.
• C-Cases with abnormal PT and aPTT and normal platelets
• D-Cases with abnormal aPTT and normal platelet count
and PT.
• E-Cases with abnormal PT and normal platelet count and
aPTT
• F-Cases with normal platelet count, PT and aPTT
These six categories of patients based on the results of
platelet count, PT and aPTT along with their further
investigative workup and diagnostic possibilities are depicted
below in Flow chart 1 and 2.
Treatment
Treatment depends on underlying cause of petechial rash-
¾ No specific treatment is required for petechial rash
associated with difficult delivery, localized to presenting
part and with normal investigations.
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¾ Suspected NAIT should be confirmed by serologic and
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DNA testing. Serology includes parents platelet antigens
and testing for presence of antiplatelet alloantibody in
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Flow chart 1: Investigative workup and diagnostic possibilities in cases with bleeding manifestations.
24
Vol. 22, No. 1, Jan. - Mar. 2008
maternal serum. DNA based typing is required to determine
paternal zygosity in implicated alloantigen, which is
important in predicting the risk of recurrence in future
pregnancies. Thrombocytopenia <30x10 9/L requires
transfusion of platelet antigen negative platelets from the
mother or from a platelet antigen negative donor. Maternal
platelets are washed and centrifuged to remove
alloantibodies and irradiated to decrease maternal
lymphocyte population which may cause graft-versus-host
disease. In the infants with platelet count between 30 and
50x109/L, intravenous IgG in a dose of 1g/kg/day on two
consecutive days may be used to effectively raise the
platelet count. Because of high risk of recurrence in
subsequent pregnancies and high risk of ICH in utero,
platelet counts in fetus should be monitored using
cordocentesis. Some centres advocate cordocentesis with
regular platelet transfusion to the fetus, while others prefer
intravenous IgG with or without steroids to the mother in
later part of pregnancy4.
¾ Autoimmune thrombocytopenia- possible therapeutic
interventions include administration of IVIg and steroids
along with platelet transfusions
 Journal of Neonatology
Flow chart 2: Investigative workup and diagnostic possibilities in cases with bleeding manifestations.
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¾ Other causes of thrombocytopenia- treat underlying cause
and platelet transfusion whenever required. Guidelines for
platelet trasfusion in neonates are given in Table 2.
¾ Hemangioma and Kasabach-Merritt Syndrome- treatment
options include steroids, surgery, embolization, irradiation
and interferon-á.
¾ DIC, Sepsis- appropriate antibiotics, platelet transfusion,
FFP, cryoprecipitate transfusions, exchange transfusion.
Some studies have used protein C and antithrombin
concentrates for DIC and purpura fulminans, although
evidence for their definitive role is lacking28-30. The
reasonable goals in DIC are to maintain platelet counts
>50 x109/L, fibrinogen concentration >1.0g/L and PT
values at normal levels for postnatal and gestational age4.
¾ VKDB- parenteral vitamin K administration, FFP.
¾ Coagulation disorders- specific factor concentrates, fresh
frozen plasma (FFP) and cryoprecipitates.
Experimental therapy
As platelet underproduction causes or contributes to most
episodes of neonatal thrombocytopenia, thrombopoietic
growth factors, such as Tpo and interleukin 11 (IL-11), may
ameliorate thrombocytopenia and provide an alternative to
the uncertainties surrounding platelet transfusion.
Thrombopoietin is the major regulator of platelet
production in humans, including neonates. Recombinant
human (rh) Tpo stimulates megakaryocyte precursor an
progenitor cells from term and preterm neonates. However,
the clinical application of rhTpo seems likely to be limited by
the development of neutralising antibodies and by the delay
of six to seven days after administration before the platelet
25
Vol. 22, No. 1, Jan. - Mar. 2008
count rises, a lag time during which many neonatal
thrombocytopenias will resolve.
IL-11 stimulates platelet production from megakaryocytes
and is now commercially available for this purpose. In animal
models, IL-11 also conveys survival benefit during sepsis and
bowel injury and has recently been shown to ameliorate
NEC. Therefore rhIL-11 treatment during neonatal sepsis and
NEC would have the potential to ameliorate
thrombocytopenia while also benefiting the underlying
conditions1.
Oprelvekin is a recombinant human interleukin-11. It is
the first available pharmacological alternative to platelet
transfusions for patients with nonmyeloid malignancies
receiving chemotherapy regimens associated with severe
thrombocytopenia. Its predominant haemopoietic activity
is stimulation of megakaryocytopoiesis. Oprelvekin
stimulates platelet progenitor cells (megakaryoblasts and
colony-forming unit megakaryocytes). The drug also
increases megakaryocyte size and ploidy. Evidence suggests
that oprelvekin reduces severe thrombocytopenia,
accelerates platelet recovery and reduces the need for platelet
transfusions in patients with nonmyeloid malignancies
receiving chemotherapy regimens associated with severe
thrombocytopenia. This drug has been tried in some of the
studies in adults only for chemotherapy associated
thrombocytopenia and yet to be tested in newborns31.
Several approaches to prevention and treatment of the
principal conditions that precipitate severe
thrombocytopenia are currently under investigation in
preterm infants, including granulocyte-macrophage colony
stimulating factor, IVIG, and pentoxifylline to reduce the
incidence of neonatal sepsis, and epidermal growth factor
for the treatment of NEC1.
 Journal of Neonatology Vol. 22, No. 1, Jan. - Mar. 2008

Table 2: Guidelines for platelet transfusion in newborn1,4-*.

Platelet count Non-bleeding neonate Bleeding neonate
9
(x10 /L)
<30 Consider transfusion in all patients Transfuse
30–49 Do not transfuse if clinically stable Transfuse
Transfuse (with HPA compatible platelets if any bleeding)
Consider transfusion if:
• <1000 g and <1 week of age
• clinically unstable (e.g. fluctuating blood pressure or perfusion)
• previous major bleeding (e.g. grade3–4 IVH or pulmonary haemorrhage)
• current minor bleeding (e.g.petechiae, puncture site oozing or blood stained
ET secretions)
• concurrent coagulopathy
• requires surgery or exchange transfusion
50–99 Do not transfuse Transfuse
www.IndianJournals.com

>99 Do not transfuse Do not transfuse

Downloaded From IP - 118.94.57.180 on dated 16-Apr-2010

IVH, intraventricular haemorrhage; ET, endotracheal.

*Patients with suspected or proven NAIT should be transfused with HPA compatible platelets, cut offs for platelet
transfusion remain the same.
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References 10. Ramful D, Carbonnier M, Pasquet M, Bouhmani B,

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APPEAL
Voluntary Health Centre, Adyar is planning to start a Neonatology and Pediatric centre in collaboration with
Sahishnatha Educational and Charitable Trust and Iyyappa samajam. The proposed cost of the building will be one
core and the cost of the equipments would be around Rs.50 lakhs Dr. S. Jayam was a well known neonatologist at
the national level and her goal was to serve middle and low income group of children of our nation, especially
Tamilnadu. Dr.S.Jayam was associated with Voluntary health services hospital in Chennai, for providing good
quality child care at low cost and started a specialized new born care unit. (Level II care) for low and middle income
group.

It was planned to start a children’s wing and level 3 NICU at voluntary health service, Adyar to provide specialized
care with advanced facility with “state of art” infrastructure. VHS has allocated the land and plan approved for this
purpose. This project will evidently serve the lower and middle income groups. Such a project will be possible only
with the cooperation of philanthropist and other groups. The NICU of this project will be named after Dr. S. Jayam
Shastri nagar Ayyappa Samajam founded by Thiru Gurusamy Sankaran (doing yoemen service to the society) is also
actively involved in this project.

We appeal to all like minded people to donate liberally towards this project. Donations may be sent by cheque or
demand draft in the name of Voluntary Health Services, Adyar, with the covering letter mentioning specifically
the amount to be used for this project only.

Donations are exempted from Income tax under sec.80 (G) of the income tax Act 1961 and Clause (11) of sub-
Section (1) of Section 35 of the Income Tax Act 1961 for research activity within this department.

Address for Correspondence :

Dr. N.S. Murali Dr. Mangayarkarasi.S
The VHS Hospital Executive Director
T.T.T.I Post SECT
Taramani, Chennai – 113. +91-9840955231
Email : vhsnsm@hotmail.com
Ph: 044-22542053

27

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