NEONATAL HEMORRHAGE

DIVISI HEMATOLOGI ONKOLOGI

DEPT. ILMU KESEHATAN ANAK
FK USU
2019
HIS1-K25(2019) 1
 Introduction
Evaluation bleeding in neonates:

Baby is well: 1. NAIT in maternal autoimmune

thrombocytopenia,amegakaryocytic
thrombocytopenia ,thrombocytopenia with
absent radii (TAR)
2. Clotting factor deficiency: Vit.K def

Sick babies: 1.thrombocytopenia cause by infection or DIC

2.Prolongation of clotting studies : DIC

HIS1-K25(2019) 2
 Causes

• 1.DIC :complication of pregnancy,hypoxia,septicaemia,RDS,NEC

• 2.Vitamin K Deficiency ( HDN )
• 3.Hereditary bleeding disorders : Hemophilia A,B ; VWD
• 4.Thrombocytopenia : Sepsis, uremia
• 5.Platelet function: uremia ,ascidosis,sepsis
• 6.Hepatic diseases Hepatitis,TORCH
• 7.Trauma : child abuse

HIS1-K25(2019) 3
Hemostasis in the newborn
1.Hemostatic mechanisms in newborn
infants is not uniformly developped
 plasminogen levels 50% of adult
 α2AP : 80% of adult
 PAI-1(plasminogen activator inhibitor-1
dan t-PA increased
 Decreased anticoagulant factors:
antithrombin,protein C and protein S
HIS1-K25(2019) 4
2.Blood vessels:
• capillary fragility is increased
• prostacyclin is increased
3.Platelets:
 Platelet adhesion is vWF increased
 Platelet aggregation abnormalities
 Platelet activation is increased
4.Bleeding time :normal because increased
platelet-vessel wall interaction, increased
vWF,HMW vWF , high Ht large red blood cell size

HIS1-K25(2019) 5
 Clinical manifestation bleeding in
newborn
• Oozing from umbilicus
• Bleeding into the scalp
• Cephalohematomas
• Bleeding after circumcision
• Bleeding from peripheral phlebothomy
sites
• Bleeding into the skin

HIS1-K25(2019) 6
Hemorrhagic disease of the newborn
Severe transient def.vit K dependent factors 
bleeding between 2 – 4 days of life :
• Gastrointestinal
• Nasal
• Subgaleal
• Intracranial
• Post-circumcision

HIS1-K25(2019) 7
Early hemorrhagic
disease of the
newborn : • Breast milk is low in
vitamin K, containing about
• The placenta transmits 2.5 μg/L (cow's milk
lipids and vitamin K contains 5000 μg/L)
relatively poorly
• The neonatal liver is
immature with respect • Late hemorrhagic
to prothrombin disease of the newborn
synthesis
• The neonatal gut is
sterile during the first – Breastfeeding
few days of life – Malabsorption
– Liver disorder

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 Nelson Textbook of Pediatric,20th ed,2016

HIS1-K25(2019) 9
The deficiency syndrome is traditionally known
as haemorrhagic disease of the newborn or
more recently, to give a better definition of the
cause, vitamin K deficiency bleeding (VKDB)

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 1.Vitamin K Deficiency Bleeding
( VKDB )
Transient deficiency of vit K-dependent factors
Moderate decreased F II,VII,IX,X normally in all
newborn infat by 48-72 hr after birth , gradually
return to birth level by 7-10 days of age

Spontaneous and prolonged bleeding

Nelson Textbook of Pediatric,20th ed,2016

HIS1-K25(2019) 11
Vitamin K
Function involved in the formation of:
• Prothrombin (factor II)
• Coagulation factors VII, IX, X

Factors dependent on Vitamin K

• Protein C, S (anticoagulants)
• Protein Z
• Bone matrix proteins
Nelson Textbook of Pediatric,20th ed,2016

HIS1-K25(2019) 12
 Classification of vitamin K deficiency
bleeding of the newborn
Syndrome Time of presentation Common bleeding
sites

Early VKDB 0-24 hours Cephalohematoma,

subgaleal ,
intracranial,
gastrointestinal
,umbilical , intra-
abdominal

Classic VKDB 1-7 days Gastrointestinal,

skin, nasal,
circumcision
Late VKDB 1-12 weeks Intracranial, skin,
HIS1-K25(2019)
gastrointestinal 13
Nelson Textbook of Pediatric,20 th ed,2016
 Epidemiology

• Adults : Vit K deficiency is uncommon

• Infants : Vit K deficiency without bleeding may

occur in as many as 50% of infants younger
than 5 days old
• The classic haemorrhagic disease : occurs in
2% if infants ot given vit K
• The prevalence of late haemorrhagic disease 20
per 100,000 live births with no prior prophylaxis
with Vitamin K
Nelson Textbook of Pediatric,20th ed,2016
HIS1-K25(2019) 14
 Conditions associated with def.vit K –
dependent factors
Neonatal newborn (normal by 3 mo of age)
prematurity:
1. Vit K responsive
2. Vit K non responsive immaturity, infection,
hypoxia , hepatic under-perfusion
Maternal medication:
Anticoagulants, antituber culosis drugs,
valproate, carbamazepine

Nelson Textbook of Pediatric,20th ed,2016

HIS1-K25(2019) 15
HIS1-K25(2019) 16
Bleeding cause :

1. Level coagulation factor : low

2. Vit K at birth : low
3. Immature liver
4. Maternal ingestion of drugs:anticoagulats,
anticonvulsant (phenytoin, primidone,
phenobarbital)
5. Malabsorption

Nelson Textbook of Pediatric,20th ed,2016

HIS1-K25(2019) 17
Laboratory: PREVENTION
• PT , APTT, blood 1 mg vit K/ im (time of
coagulation time : birth)
prolonged
• Level Factor II, VII, IX, X Tratment :
are decreased 1. Vit K1 ; 1-5 mg / IV -
• Bleeding time, slowly
fibrinogen, F V, VIII and 2. Fresh Frozen Plasma :
platelet ,capllary serious bleeding,
fragility and clot premature infant,liver
retraction: Normal disease
Nelson Textbook of Pediatric,20th ed,2016
HIS1-K25(2019) 18
 2.Hepatic dysfunction

• Transient inability of the newborn’s liver to

synthesize coagulation factors  result of
immaturity ,infection, hypoxia, underperfusion of
the liver
• Clin Manifest : variable and dependent on
underlying disorder, symptom : ecchymosis,
petechie, ICH, GI bleeding
• Lab : >> PT, aPTT, TT, BT; Thrombocytopenia; <<
FVII, FV, Fibrinogen, Plasminogen
• Tretament : FFP, Cryoprecipitate, Platelet transf.,
and Vit K administration Neonatal Hematology, 2005
Nelson Textbook
HIS1-K25(2019) of Pediatric,20th ed,201619
3.Disseminated Intravascular Coagulation
(DIC)

Systemic activation
of coagulation

Intravascular Depletion of platelets

deposition of fibrin and coagulation factors

Thrombosis of small Bleeding

and midsize vessels
with organ failure
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Pathogenesis of DIC

Release of
thromboplastic
material into Consumption of
circulation coagulation factors;
presence of FDPs
Coagulation Fibrinolysis
 aPTT
 PT
Fibrinogen  TT
Thrombin Plasmin  Fibrinogen

Presence of plasmin
Fibrin  FDP
Monomers Fibrin(ogen)
Degradation Intravascular clot
Products  Platelets
Fibrin Schistocytes
Clot
(intravascular) Plasmin
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………...Disseminated Intravascular Coagulopathy

• Intravascular consumption of platelet and plasma clotting

factor coagulopathy in vasculature  bleeding
• Premature with asphyxia , hypoxia , acidosis ,
shock, hemangiomas, Infection
• Treatment : 1. primary underlying disease
2. Platelet transfusion
3. Fresh frozen plasma
4. Coagulation inhibitor concentrate
(ATIII)

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 3.Swallowed blood syndrome

• Blood or bloody stools are passed on 2nd – 3rd

day of life
• Blood from swallowed during delivery or fissure
in the mother’s nipple
• Apt test : differentiation blood from maternal
(yellow-brown color) or infant (persistent pink)

Nelson Textbook of Pediatric,20th ed,2016

HIS1-K25(2019) 23
 4.Neonatal alloimmune thrombocytopenia
(NAIT)
• Incompatibility between parental platelet
antigens leading to maternal antibodies to
antigens expressed by fetal platelets. Mother
has a normal platelet count

• First pregnancy can have affected child (unlike

neonatal Rh disease) 50% of cases are first
born infant , antigenic exposure occurs “early
pregnancy” (unlike Rh ,primarily at delivery)

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• Human platelet antigen 1 (HPA-1 or PLA-1)
incompatibility accounts for 80% to 90% of cases of
NAIT
• Incidence of NAIT is 0.05% to 0.1%
• Typically infants : healthy full-term babies, generalized
petechiae ( 80% of cases)  ecchymosis ,
cephalhematomata , bleeding from umbilicus ,skin
puncture site, gastrointestinal or renal 25
• Thrombocytopenia (< 50,000/mm3) in 90% of cases
• Intracranial hemorrhage in 11% of cases

Nelson Textbook of Pediatric,20th ed,2016

HIS1-K25(2019) 25
Clinical manifestation

 severe, generalized petechiae

 rash or purpura
 or normal at birth and may develop symptoms
and signs during 2-3 day post-partum.
 Severe complication is intracranial
hemorrhage which is seen in approximately
10-15% cases and half of these occurs in
utero with neuro- developmental sequele

Nelson Textbook of Pediatric,20th ed,2016

HIS1-K25(2019) 26
Treatment recommended

• Platelet transfusion
• Maternal donor platelet or washed maternal
platelet
• IVIG 1 g/Kg/day  for 1-3 days ,
• Methylprednisolone 1 mg IV every 8 hours
• Follow-up is necessary until platelet count
above 30.000 -50.000/mm3( goal platelet )

Nelson Textbook of Pediatric,20th ed,2016

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Diagnosis requires demonstration of
maternal and fetal platelet incompatibility
and absence of antigen in mother's serum,
which is present in the child

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 5.Neonatal autoimmune thrombocytopenia
• Transplacental passage of maternal platelet
autoantibodies occurs in babies born to
mothers with idiopathic thrombocytopenic
purpura (ITP) or systemic lupus
erythematosus (SLE)

• Around 10% of infants of affected mothers

develop thrombocytopenia

Nelson Textbook of Pediatric,20th ed,2016

HIS1-K25(2019) 29
• Thrombocytopenia is usually mild and ICH
is rare (<1% of at-risk babies)

• Severe thrombocytopenia treatment with

IVIG 1 g/kg for 2 days is usually effective

Nelson Textbook of Pediatric,20th ed,2016

HIS1-K25(2019) 30
Neonatal thrombocytopenia associated with
aneuploidies
• Thrombocytopenia is seen in neonates with
– Trisomy 21
– Trisomy 18
– Trisomy 13
– Turner syndrome
– Triploidies

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Treatment :
• Platelet transfusions
• Thrombopoietic growth factors
 Thrombopoietin
• This is the major regulator of platelet production in
humans, including neonates
• Recombinant human (rh) Tpo stimulates
megakaryocyte precursor and progenitor cells from
term and preterm neonates
 IL-11
• This stimulates platelet production from
megakaryocytes
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Guidelines for platelet transfusion thresholds for neonates

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DIAGNOSTIC APPROACH TO
AN INFANT WITH
THROMBOCYTOPENIA

Neonatal Hematology, 2005

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