1. DR RAGHAVENDRA.M.D.
FELLOW IN NEONATOLOGY

2.  The hemoststic mechanism in neonate different from
older children.
 There is decreased activity of several clotting factors,
diminished platlet function and sub optimal defence
against clot formation
 On presentation
 Stabilize
 Assess vitals – severity of disorder
 Replace fluids adequately
 Monitor
 Evaluate for cause

3. Causes of Bleeding.
 Coagulation defects
 Platlet factors defect
 Fibrinolytic dysfunction
 Vascular causes
 miscellaneous

4. Clotting factors defects
1)Transitory deficiencies :
Procoagulant vit k dependent factors 2 ,7,9 and 10 and
anticoagulant protein C and S and may be attenuated by
• Administration of total parentral alimentation or
antibiotics or lack of administration of vit k to
premature infants.
• Term infant may develop vit k deficiency by day 2 or 3
if they are not supplemented vit k.
• Mother might have received certain drug during
pregnancy that can cause bleeding in first 24hr of
infant life like phenytoin, phenobarb, salicylates
warfarin.

5. 2)Disturbance of clotting : may be related to
associated disease such as DIC ,due to infection, shock
anoxia, NEC ,renal vein thrombosis, vascular catheter,
liver disease.
3)Inherited abnormalities of clotting factors
X linked recessive (present in male,affected is female)
a)Factor 8 levels are decreased in newborn with
hemophilia A (1 in 5000).
b) Heamophilia B or christmas disease is due to
deficiency of factor 9 (1 in 25000)

6.  Autosomal dominant: (expressed in boys and girl
with one parent affected)
 Von willebrand disease is due to decreased levels or
functional activity of VW factor.It is the most common
inherited coagulation defect.
 Dysfibrinogenemia is due to fibrinogen structural
mutation.
 Autosomal recessive: (occur in both boys and girls
born to carrier parents)
 Deficiency of factor 11, 7 ,5,10,2, fibrinogen and 13 are
all encoded by autosomal gene.

7. COMMON COAGULATION DISORDER
• Haemophilia A and B
• Von- willebrand disease
• Factor VII, X,XII
deficiency
• afibrinogenesis
Inherited
• Liver disease
• Vit k deficiency
• Warfarin overdose
• DIC
acquired

8. CLASSIFICATION OF PLATELET DYSFUNCTION
• Bernaud- soulier syndrome
• Glanzmann’s thrombasthenia
• Wiskott- aldrich syndrome
• Gray platelet syndrome
• Medications
• Chronic liver failure
• Cardiopulmonary bypass
Qualitative
• Decreased production
• Increased destruction
quantitative

9. DIFFERENCES IN BLEEDING PATTERN
PLATELET DISORDER COAGULATION
DISORDER
SITE OF BLEEDING Skin, mucous membrane Deep in soft tissue, joints,
muscles
PETECHIAE yes no
ECCHYMOSES Small, superficial Large, deep
HEMARHTROSIS/
MUSCLE BLEEDING
Extremely rare common
BLEEDING AFTER
MINOR TRAUMA
yes no
BLEEDING AFTER
SURGERY
Immediately, mild Delayed(12 days), severe
EXAMPLES vWD
ITP
Hemophilia A, B

10. Vascular causes of bleeding
 Pulmanory and CNS hamorrage
 Henoch schonlein purpura
 Connective tissue disease
 Scurvy
 Hemanangioma.
 Hereditary hemorrhagic telangiectasia
Miscellaneous problems:
Trauma: rupture of spleen or liver with breech delivary.
Subdural hematoma, subgaleal and cephalohematoma.

11. Hematologic consequences to the fetus due to
maternal disease
 Diabetes : polycythemia and thrombosis
 Hypertension : neutropenia, thrombocytopenia
 SLE : thrombocytopenia or thrombosis
 Smoking : polycythemia
 Medications : aspirin  effects on hemostasis
 Chemotherapy  thrombocytopenia
 Intrauterine infection : anemia (hemolytic),
thrombocytopenia, consumptive coagulopathy.

12. Clinical approach to the bleeding neonate
 A detailed history including detailed past history and
family history.
 A careful physical examination.
 Screening tests.
 Specific tests for hemostasis as required,
need to be done to define the defect .

13. HISTORY TAKING :
Is the infant ‘sick’ or ‘well’ at the onset of bleeding?
Sites of bleeding.
Onset, severity and duration
Spontaneous or after trauma.
Symptom correlate with degree of injury or trauma?
Does bruising occur spontaneously?
If there was any chord bleeding?
Has vitamin K been given to the infant?
Is there a family history of bleeding disorder?
History of maternal illness, maternal infection, drug intake

14. Presentations in newborn are unique
EXCESSIVE BLEEDING can appear as
 Expanded cephalhematoma.
 Prolonged bleeding after circumcision.
 Oozing from venipuncture site and line placement site.
 Bleeding from umbilicus .
Sick neonate may present as
 Bleed from bladder –haematuria
 Mucous membrane bleed
 IC bleed
 Pulmonary haemorrage

15. PHYSICAL EXAMINATION
VWD, PLATELET FUNCTION DEFECTS CLOTTING FACTOR DEFICIENCY

16. Examine for
 Degree of anemia
 Ecchymoses
 Petichiae
 Vascular malformations
 Rashes
 splenomegaly
 Rule out local causes of bleeding

17. ON EXAMINATION
 Sick infant –DIC, infection, liver diseases
 Well infant –VKDB ,Clotting factor deficiency.
 Petechiae, small ecchymosis –platelet disorder
 Large bruises –clotting factors defeciency, DIC, liver
disorders ,or vit k defeciency
 Splenomegaly – congenital Infection/erythroblastosis.
 Jaundice –TORCH infections or LIVER disease
 Abnormal retinal finding-TORCH infection

18. Bleeding Neonates: sick or well
Acquired Causes Most Common
 Acquired coagulopathy: More likely in sick infants
 Inherited bleeding disorders or immune thrombocytopenias:
more often in well infants
 Alloimmune thrombocytopenia (NAIT)
Review obstetric and neonatal course
DIC
Acidosis, RDS, meconium aspiration, hypothermia, NEC,
sepsis, exchange transfusion, etc
Review family history of bleeding
Immune thrombocytopenia (ITP) or Neonatal

19. Likely diagnosisPTTPTPlatelets
Clinical
Evaluation
DIC1+1+D-Sick
Platelet consumption ( infection,
necrotizing enterocolitis, renal vein
thrombosis )
NND-
Liver disease1+1+N
Vasculitis (hypoxia, prematurity,
acidosis, hyperosmolality )NNN
ITP, occult infection, thrombosis, B.M.
hypoplasia or infilterationNND-Healthy
Hemorrhagic disease of newborn ( vit.
K deficiency )
1+1+N
Hereditary clotting factor deficiencies1+NN
Bleeding due to local factor ( trauma,
anatomic anomalies);
NNN
PT = prothrombin time; PTT = partial thromboplastin time; D- = decreased; 1+ = increased; DIC =
disseminated intravascular coagulation; N= normal .

20. The Workup Continues…
 • False positive evaluations
– Need to interpret lab results in context of
developmental hemostasis
–Pediatric reference ranges
 • False negative evaluations
– Often miss mild disorders in newborns
(Mild hemophilia, type 1 and 2 von Willebrand disease)
– Platelet function disorders not evaluated
– Rare bleeding disorders

21. Swallowed blood syndrome
 Blood or bloody stools are passed during the 2nd or 3rd day of
life due to swallowing of maternal blood during delivery or
from a fissure in the mother’s nipple .
 It may be confused with hemorrhage from GIT of the
newborn .
 The Apt test is used to DD, based on the fact that the
infant’s blood containing hemoglobin mostly HbF is alkali-
resistant where as the maternal blood (Hb A) forms alkaline
hematin on addition of alkali .

22. Laboratory tests
TEST FOR PLATELET DISORDER.
 BLEEDING TIME: assesses the function of platelets & their interaction
with vascular wall. (Normal range:4-8 minutes)
 PLATELET COUNT: normal (150,000-400,000)
 PLATELET FUNCTION ANALYSIS (PFA-100)
 PLATELET AGGREGATION STUDY: with ADP, Epinephrine, collagen
, thromboplastin and Restocetin is done.
TEST FOR COAGULATION FACTOR.
 aPTT: measure the initiation of clotting at level of intrinsic factor
VII,IX,XI (normal 25-40s.)
 PT: measures the extrinsic clotting limb i.e. II,V,VII,X. (12-14s)
 THROMBIN TIME:- measures final step of clotting cascade. (Normal
11-15 s) prolonged in fibrinogen deficiency.
 Fibrinogen.
 D Dimer assays.
Peripheral smear – platelet and RBC morphology

23. Treatment of bleeding in neonate
 1. I.V. infusion of 1-5 mg vit. K1will lead to cessation of bleeding within a few
hours.
 2. Fresh frozen plasma (10 ml/ kg) in cases of serious bleeding, premature
NB, those with liver diseases and ineffective vit. K therapy.
 3. Whole blood transfusion (in case of marked hemorrhage ) may be required
 4-Treatment of the underlying cause:
* Platelets : In case of thrombocytopenia, 1 unit of platelets given to a 3-kg
infant will raise the platelet count to 50.000-100.000 / mm.
* Clotting factor concentrates : In cases of inherited deficiencies of F8, or
F9, but plasma may be sufficient .
* Treatment of disseminated intravascular coagulopathy
a. Treatment of the underlying cause ( sepsis, NEC ).
b. If the bleeding persists : Exchange transfusion with fresh whole blood .
c. If thrombosis of large vessels : Heparin : bolus of 25-35 units / kg, followed
by10-15 units / kg / hr. as a continuous infusion. Keep the PTT at 1.5-2 times
normal.

24. (Hereditary Clotting Factor Deficiency)
HEMOPHILIA A OR B
Most common inherited clotting disease.
 Hemophilia A and B are inherited bleeding disorders
caused by deficiencies of clotting factor VIII (FVIII) and
factor IX (FIX), respectively.
They account for 90-95% of severe congenital coagulation
deficiencies.
Affect all racial groups.
X-linked recessive disorders; therefore, they affect males
almost exclusively. Reports of affected females are rare.

25. Hemophilias may be undiagnosed in the newborn. It’s
noticed when a child begin to crawl & walk because
mobility causes the initiation of easy bruising,
intramuscular hematoma & hemoarthrosis.
In the newborn factor VIII level may be artificially
elevated because of acute phase response elicited by the
birth process. In contrast, factor IX level is
physiologically low in the new born.
LABORATORY FINDINGS:
Reduced level of factor VIII or factor XI.
Prolonged Clotting time & aPTT.
Normal Platelet count , BT, PT & thrombin time.
Prolonged thromboplastin generation time.

26. Von Willebrand disease
• VWD is the commonest inherited bleeding disorder, with an
estimated prevalence of 0.8–1.3%
• Inherited as an autosomal dominant disorder.
• Both superficial bleeding problems and ICH have been reported in
affected neonates.
• Type IIb vWD can also be recognized at this time due to the
presence of thrombocytopenia
• Most other forms of vWD are masked by physiologically elevated
levels of vWF and cannot be diagnosed in neonates other than by
molecular analysis
DIAGNOSIS:
 Type III vWD: low levels of both FVIII and vWF.
 Some cases of type II vWD may also be diagnosed in the neonate
where there is reduced vWF activity.

27.  Moderate transient deficiencies of vitamin K dependent factors 2, 7, 9,10
1. Reduced body store of vit K of the newborn due to lack of free vitamin K in
the mother (more common among the preterm infants).
 2. No vitamin K administration after birth. (Breast milk is a poor source of
vitamin K) more common in breast-fed infants than formula-fed ones ).
 3. Liver immaturity or disease.
 4. Malabsorpation disease (biliary atresia, cystic fibrosis, hepatitis).
 5. Absence of bacterial intestinal flora (that form vitamin K): Total parenteral
alimentation , Broad spectrum antibiotics.
 6. Maternal medication : phenytoin, phenobarbital, salicylates, rifampcin and
isoniazid

28. EARLY VKDB
 Least common form.
 The onset: within the first 24 hours of life.
 Bleeding pattern is variable but can be serious,
ICH does occur.
 Typically,(not exclusively), associated with the drug
ingestion during pregnancy.
 Warfarin, anticonvulsants and the antituberculous drugs
rifampicin and isoniazid have all been implicated.
MANAGEMENT
 At risk mothers should be given about 10 to 20 mg/day of
vitamin K orally for 15 to 30 days before delivery.
 When Warfarin is to be prescribed it is advised that it is
avoided between wks 6 &12 of gestation(Teratogenic) and
close to term (neonatal bleeding.)

29. CLASSICAL VKDB
 Estimates of the frequency of classical VKDB in the
absence of vitamin K prophylaxis vary considerably (0.25 –
1.7%) and depend particularly on the method of feeding
employed.
 They are almost exclusively breast-fed.
 Typically presents between days 2 and 5 in infants who
appear otherwise well.
 Bruising, purpura and gastrointestinal hemorrhage are
typical presentation.
 Bleeding from the umbilicus and mucous membranes is
also common, but ICH appears to be relatively infrequent.
MANAGEMENT:-
I/V or S/C Vit K
Transfusion therapy
Supportive treatment

30. LATE VKDB
 The onset is after the first week of life, with a peak
incidence between 2 and 8 weeks.
 ICH is seen in around 50% of cases and is associated
with significant morbidity and mortality.
 Breast-feeding and failure to receive vitamin K at birth
are frequently documented risk factors.
 it can be the presenting feature of cystic fibrosis,
celiac disease, anti-antitrypsin deficiency and biliary
atresia.
 In other cases it is thought that transient, mild
abnormalities of liver function may contribute to
cholestasis and temporarily reduced vitamin K
absorption.

31. Disseminated Intravascular Coagulation
 DIC is a clinicopathologic syndrome resulting into
widespread intravascular coagulation induced by
procoagulants that are introduced into or produced in the
blood circulation and overcome the natural anticoagulant
mechanisms.
 Spectrum of DIC includes:
 Thrombosis
 Bleeding
 Progressive organ dysfunction
 The end result is usually hemorrhage.

32. Management of DIC
DIC is a secondary phenomenon ,management is reversal of the
underlying disease process.
 Supportive therapy with FFP, cryoprecipitate and platelets to
maintain adequate hemostasis.
 The platelet count should be maintained above 50 × 109/L.
 FFP (10 –15 mL/kg) can be used to replace hemostaticproteins,
including the coagulation inhibitors ATIII, protein C & S.
 Cryoprecipitate (5 –10 Ml/kg) is a better source of fibrinogen,
which should be maintained above 1 g/L.
 Red cell concentrates are also frequently required.
 Exchange transfusion may be undertaken in sepsis induced DIC.

33. REFERENCES
 Fanaroff and martin neonatal –perinatal
medicine 9th edition 2012 ,pg no 1334-1345.
 Avery’s neonatology 6th edition, pg no 1190-1195.
 Manual of neonatal care, john p cloherty
7th edition pg no538-545
 Care of newborn ,Meherban Singh
7THEdition pg no 355-365.
 Google search :oskis text book of pediatrics .
 Case reports from journals .