Bleeding neonate

Differences in a neonate
• Decreased activity of clotting factors
• Diminished platelet function
• Suboptimal defense against clot formation
• A full term infant will have normal adult values for
PT, Fibrinogen, Platelet count and factor VIII
• Fibrinogen and platelets – Normal at birth, even in
extremely preterm infants
• vWF, α2 macroglobulin – increased in term birth

Keeling’s neonatal and fetal pathology

Hemostatic Mechanism
The classic hemostatic mechanism
include:
-Vascular response

-Platelet hemostatic activity

-Coagulation factors
 Vitamin K
• 10fold gradient between maternal
and fetal circulation.
• Post translational modification of
Vit K dependent zymogen
proteins.
• Carboxylation of gamma position
of 9-12 Glu residues near NH2
terminus.
• Formation of Gamma-carboxy
glutamic acid (Gla)
• Capacity for calcium mediated
binding to phospholipid surfaces.
Platelet defect

Clotting defect

Vessel

Miscellaneous
 Platelet problems
1. Qualitative disorders:
- Glanzman’s thrombasthenia.
- Bernard-Soulier syndrome
- Platelet type VWD
- Transient= Mother using antiplatelet agents
2. Quantitative disorders:
a)Immune thrombocytopenia
Maternal ITP OR NAIT
b) Maternal Preeclampsia, HELLP syndrome or severe
uteroplacental insuffuciency.
c) DIC due to infection or asphyxia
d) Inherited marrow failure syndromes :
- Fanconi anemia
-congenital amegakaryocytic thrombocytopenia
e) Congenital leukemia

f) Inherited thrombocytopenia syndromes -gray platelet syndrome

-Macrothrombocytopenias : May-Hegglin syndrome

g)Platelet consumption in clots/ vascular disorders

eg. Vascular malformations, NEC.

 Clotting factor
Deficiency of clotting factors:
1.Transitory deficiencies-
 Deficiency of vitamin K dependent C.F- II, VII, IX, X
 Deficiency of anticoagulant proteins C & S.
Causes:
a. Total parenteral nutrition or antibiotics
b. Lack of administration of vitamin K .
c. Drug intake in pregnancy
eg. Phenytoin, Phenobarbital, Salicylates ,Warfarin
(Interferes with the synthesis of vit. K dependent factors )
 .
2 Disturbances of clotting
- Related to DIC due to infection, shock, hypoxia, NEC, renal vein
thrombosis, use of IV cannula.

3. Inherited abnormalities of C.F.

a. X-Linked recessive diseases-
i. Hemophilia-A : Factor VIII deficiency.
ii. Hemophilia-B : Factor IX deficiency.
b. Autosomal dominant diseases:
i. Von Willebrand disease – Deficiency of VWF which is a carrier of
factor VIII & as a platelet aggregation agent.
c. Autosomal recessive diseases:
i. Severe factor VII & factor XIII deficiency – intracranial hemorrhage
in neonates
ii. Factor XI deficiency –
unpredictable bleeding during surgery/trauma.
 Vascular origin:
- Pulmonary haemorrhage
- A-V malformations
- CNS haemorrhage
- Hemangiomas
 Causes of bleeding in a neonate
Well Baby Sick Baby
• Thrombocytopenia
• Neonatal alloimmune (acquired)
thrombocytopenia • DIC
• Maternal ITP • Liver failure
• Congenital • Bone marrow infiltration
thrombocytopenia
• Congenital dis. of platelet
function
• Hemophilia and other
clotting factor deficiencies
• Vitamin K deficiency
 History
• Family history of excessive bleeding or thrombosis
• Maternal systemic illness (infection, HELLP syndrome)
• Maternal drug intake
– Aspirin
– Thiazides
– AED
– ATT - HR
– coumarins
• Birth history
– Instrumental delivery
– Hypoxia at birth
– Resuscitation at birth
 Examination

• Sick or well baby

• Pallor
• Petechiae/ ecchymosis/ mucosal bleeds (platelet
abnormality)
• Large bruises (clotting factor deficiency)
• Splenomegaly (Congenital infection/congenital leukemia)
• Jaundice (infection/ resorption of a large hematoma)
• Presence of abnormal retinal findings (congenital infection)
• Signs of shock/CCF
• Presence of physical abnormalities
 Labs
Peripheral smear
• Platelet number
• Platelet morphology
– Small platelets – Wiskott Aldrich syndrome
– Large platelets – Bernard Soulier syndrome
• Platelet aggregation
• DIC- Fragmented RBCs, thrombocytopenia, schistocytes,
leukocytosis with a left shift, mild polychromatophilia, and
large young platelets in fulminant cases.
 Labs
• PCV
• PT/APTT
• Apt test
• Platelet function – PFA, template bleeding
time
• Fibrinogen
• D-dimer assay
• Coagulation factor assay
3. PT
4. APTT
5. D-Dimer assays: Measure fibrin
degradation products in DIC & Liver
diseases causing defective clearing of
fibrin split products.
6. Specific factor assays & Von
Willebrand assay: For patients with +
ve family h/o.
 Laboratory findings
Laboratory Studies Likely Diagnosis Other useful tests

Platelets PT APTT
SICK INFANTS

N N

N
 Laboratory findings
Laboratory Studies Likely Diagnosis Other useful tests

Platelets PT APTT
SICK INFANTS
DIC, sepsis, hypoxia, acidosis, cold Fibrinogen, FDP, Sepsis
stress screen

Platelet consumption LFT, Albumin

(NEC, Renal vein thrombosis,
N N marrow infiltration, Sepsis)

Liver disease
N
 Laboratory Studies Likely Diagnosis Other useful tests

Platelets PT APTT

HEALTHY INFANTS

N N

N N

N N N
 Laboratory Studies Likely Diagnosis Other useful tests

Platelets PT APTT

HEALTHY INFANTS
Immune thrombocytopenia Maternal platelet count,
N N Bone marrow hypoplasia Platelet antigen typing,
Bone marrow, Fibrinogen,
FDP, Factor VII & IX assays

N Vitamin K Deficiency

N N Heriditory C.F. deficiencies B.T.

Bleeding d/t local factors, Platelet aggregometry

N N N Plt function anomalies, Urea clot solubility
Factor XIII deficiency(rare)
 Treatment Of Bleeding
A. Inj Vitamin K1 (Aquaminophyton)
- 1 mg IV or IM if not given at birth.
- Infants on TPN
- Infants on Antibiotics > 2 weeks: at
least 0.5mg Vit K weekly.
- Preferred rather than FFP for prolonged
PT & PTT, FFP should be reserved for
emergencies.
B. FFP:
- 10ml/kg IV for active bleeding
- Repeated 8-12 hrly as needed.
- Replaces C.F. immediately.
C. Platelets:
- 1 Unit of platelet raises count by
50,000-10,000/mm3.
- Platelet count slowly decreases if stores
3-5 days.
D. Fresh whole blood:
- 10ml/kg
- Can be repeated after 6-8 hrs as needed.
E. Clotting factor concetrates
- Severe VWD :
- VWF containing plasma derived factor VIII
concetrate.
- Known deficiency of factor VIII or IX :
Recombinent DNA derived factor VIII and
IX concetrate
F. Disorders due to problems other than hemostatic
proteins :
- Rule out the underlying possibilities
- eg. Infection, Liver rupture, catheter, NEC.

G. T/t of specific disorders :

1. DIC :
- Treat the underlying cause i.e. sepsis, NEC
- Make sure that Vit K1 has been given.
- Platelets/ FFP to keep platelet counts > 50,000/ml
and to stop bleeding.

- If bleeding persists,
i. Exchange transfusion with fresh whole blood
/Packed RBC/Platelets/FFP
ii. Continuous transfusion with platelets, packed
RBCs or FFP as needed.
iii. For hypofibrinogenemia : Cryoprecipitate
(10ml/kg)
2. Haemorrhagic disease of newborn
- Incidance is 1:200 neonates (Not given Vit-K).
- For active bleeding : 10ml/kg FFP & Inj
Vitamin K 1mg IV .
- If mother is on t/t with Phenytoin, primidone,
Methoximide or Phenobarbital, the infant
may be deficient in vit K
.Inj Vit K 10mg IM 24 hours before delivery
. Newborn is monitored for signs of bleeding,
PT, APTT.
3. Delayed Hemorrhagic disease of
newborn:
- Occurs at 4-12 weeks of age
- Not very common in infants who received Vit
K at birth.
- Exclusively breast feeding infant
- Infant on t/t with broad spectrum antibiotics
- Infant with malabsorption
T/t: Vitamin K1- 1mg/week orally for first 3
months of life.
 Neonatal Alloimmune
Thrombocytopenia
• Maternal Ab against fetal Ag – PLA 1 Ag
• 1 in 1000 infants
• 50% in first preg; subsequently more severe
• Skin > IC, GI bleeds
• PC <10,000 in a well baby; Mother PC normal
• Determination of Ab
• Rx: Maternal platelet transfusion (sympt,
extremely low PC)
IVIg (to mother >32wks, post-natal to infant)
 Maternal ITP
• Symptommatic thrombocytopenia
• Less frequent, less severe than NAIT
• Mother – thrombocytopenia
• Rx: Post natal steroids, IVIg to baby
(bleeding
 Congenital thrombocytopenias

1) TAR syndrome
• Thrombocytopenia
• Absent Radius syndrome
• Normal thumb
 Congenital thrombocytopenias

2) Fanconi Anemia
• Thumb anomalies
• With or without short
radii
• Small length, HC
 Congenital thrombocytopenias

3) Wiskott Aldrich syndrome

• Thrombocytopenia (Small platelet),
↓IgM, Eczema
 Congenital thrombocytopenias
4) Amegakaryocytic thrombocytopenia
↓PC
without skeletal abnormalities
assoc with CHD
50% severe Hemorrhage in 1st year
of life.

5) Downs syndrome
transient ↓PC/ thrombocytosis
with/without other cytopenias
 Congenital thrombocytopenias

6) Neonatal leukemias
• Skin lesions of
extramedullary
haematopoesis –
blueberry muffin lesion
• Almost always exhibits
obvious abnormalities in
other cell lines
• Sick baby
 Congenital disorders of Platelet
function
1) Glanzman Thrombasthenia
• AR; mutation in GP IIb/IIIa
• Absent/ quantitively decreased/ functionally
abnormal receptor
• Inteferes with platelet aGGreGation
• Normal PC
• Function assessed by PFA-100/
template binding time/ plt aggregation
– severely decreased
 Congenital disorders of Platelet
function
2) Bernard Soulier syndrome
• AR; mutation in GP Ib/IX
• Interferes platelet adhesion to collagen via
vWF
3) Ehler Danlos syndrome
•• Mild
Mostthrombocytopenia
AD with Giant platelets
• Coag screen Normal
• Template bleeding ↑
• PFA Normal (exogenous collagen incorporated)
• Family history of joint hyper-extensibility, lax skin,
impaired wound healing, early pregnancy losses
Hemophilia A Hemophilia B
• FVIII deficiency • FIX deficiency
• XLR • XLR
• 1 in 10,000 live births • 1 in 30,000 live births
• Easily diagnosed • Difficult to diagnose

 Sub galeal bleeds, large caput succedaneum,

retroperitoneal hematomas,
subcapsular/parenchymal h’age of the liver
 Extensive bleeding from skin puncture sites and
circumcision
 ↑APTT, Normal PT
 Coagulation profile
 Vitamin K deficiency
syndromes
Type EARLY CLASSIC LATE
Time of onset First 24hrs 1-7days 1-8weeks

Site of bleeds Intra-cranial Umbilical stump Intracranial

intra-thoracic GIT GIT
intra- abdominal Nose, skin
following surgical
procedures
Cause Maternal Poor vitamin Fat
anticonvulsants intake usually in malabsorption
Antibiotics breastfed infants (biliary atresia,
ATT cystic fibrosis, α1
antitrypsin
deficiency)
 Other causes
• Acquired thrombocytopenia
• Infection
• Asphyxia
• Hypoxia/acidosis
• Venous thrombosis

• Disseminated Intravascular Coagulation

• Sepsis
• NEC
• Hypoxia/acidosis
• Liver failure
 Liver failure
• Sites of bleeding – Skin/ GI/ IC
• Cause of liver failure – infection (hepatitis),
hypoxia/ischemia, metabolic disorders, neonatal
haemochromatosis.
• Pathogenesis - failure of new protein
consumption of clotting factors and
platelets
inhibition of normal coagulation by
faulty clearance of
fibrin and FDP//
• ↑↑PT – def of FVII – acute liver synthesis
 References
Cloherty manual of neonatal care-Seventh
edition