1. Dr Neoh Hui Pheng
Hospital Seberang Jaya

2.  Def : consequence of tightly regulated
processes that maintain blood in a fluid,
clot-free state in normal vessels while
introducing the rapid formation of a
localized hemostatic plug at the site of
vascular injury.
 Mechanism
 vasocontriction
 formation of platelet plug
 coagulation cascade
 fibrinolysis

8. Comparing coagulation factor and platelet defects
Coagulation factor defects Platelet disorders and von Willebrand's disease
Bruising on trunk and limbs Large bruises Small bruises
Bleeding from cuts Relatively slight Profuse
Nosebleeds Uncommon Common, frequently profuse and of long duration
Gastrointestinal bleeding Uncommon Common
Haematuria Common Rare
Haemarthrosis In severe haemophilia Very rare
Bleeding after surgery or dental extraction Up to a day's delay before bleeding occurs Immediate bleeding

10.  Defect in clotting mechanism
 HemophiliaA : Deficiency of FactorVIII ( 85%)
Hemophilia B : Deficiency of Factor IX ( 15%)
 70 % X linked recessive. 30 % spontaneous
mutation with no family hx.

11.  Rarely,bleeding symptoms may present from
birth ( Factor 8 and 9 do not cross placenta)
- Intracranial hemorrhage /prolonged oozing
from heel stick/venepuncture sites.
- Most children present with easy bruising when
crawling and walking ( ard 9-12 months)
- Hemarthrosis – characteristic.
- large joints ( ankle, knee, elbow ) – swollen and
painful
( ankle joint : often the earliest joint involved. )

12.  Other bleeding tendencies: Epitaxis, gum
bleeding , hematuria.
 Bleeding can be spontaneously, after trauma
, operation or dental procedures.
 Lungs/ CVS / PA : unremarkable

13.  FBC
 Coagulation screen : PT/ APTT
 RP / LFT
 Specific factor assay : Factor 8 or factor 9
 Von willebrand screen even ifAPTT normal .
Others :
- Infective screen ( at diagnosis and yearly) :
Hep B/ Hep C /HIV
- Platelet aggregation if highly suspicious of
platelet defect.

14. Classification Clinical manifestation
Severe
(<1% of normal)
•Manifest in infancy when child reaches toddler stage
• Spontaneous bleeding – in muscles or joints (haemarthroses)
• Excessive bleeding after minor trauma, postoperatively, or
after intramuscular childhood vaccinations
Moderate
( 1-5% of normal)
•Manifest after 2 years of life
• Moderate trauma causes bleeding episodes
• Occasionally spontaneous bleeding occurs
Mild
( >5 % - < 40% of
normal)
•Often diagnosed in teenagers and adults
• Significant trauma/surgery or dental procedures to induce
bleeding
• No spontaneous bleeding

15.  First Aid ( PRICE) : Pressure, Rest, Ice,
Elevation
 FactorVIII /IX replacement
Infuse factor 8 by slow IV push at the rate not exceeding 100U/
min in young children.
 FFP and cryoprecipitate should not be used as there
is higher risk of viral transmission.

16. Type of bleed FactorVIII dose Factor IX dose
Hemarthrosis 20U/kg 40 U /kg
Soft tissue or
muscle bleeds
30-40U/kg 60-80U /kg
Intracranial
hemorrhage or
Surgery
50U /kg 100 U /kg

17. Calculate the required dose:
- FactorVIII : ( % rise reqd) x ( wt in kg) x 0.5
- Factor IX : (% rise reqd) x ( wt in kg) x 1.4
Type of bleed % rise required duration
Haemarthroses 30-40% 2-3 days
Soft tissue /Muscle
bleed
( Risk of
compression/comp
artment syndrome)
40-50% 4-5 days
Intracranial bleed
/operation
100% 7-10days

18.  Analgesic often not required ( as there is
rapid pain relief after missing factor
concentrate is infused)
- AVOID I.M injection
- Don’t use Aspirin/NSAIDs – affect platelet fx
- Acetaminophen with or without opioids can
provide adequate pain control

19.  Dental care is required as dental caries are a
regular source of bleeding.
 In severe cases, dental clearance with factor
replacement will be required.
 Medic alert bracelet
 Register with hemophilia society.

20. 1) Joint destruction : Recurrent hemarthrosis
into the same joint  osteoarthritis and joint
deformity.
 Preventable by prompt and adequate factor 8
replacement.
2) Infection : Hep B/Hep C and HIV
- All hemophiliacs must be immunised with
Hep B

21. 3) Inhibitors: Antibodies directed against the
exogeneous FactorVIII and IX neutralising the clotting
activity.
Can develop at ANY age, but usually 10-20 exposure
days.
Suspected when there is lack of response to
replacement therapy instead of higher doses.
 2 agents – “bypassing” the deficient clotting factor :
i) Recombinant activated FactorVII ( rfVII or
Novoseven)
ii) FEIBA ( Factor Eight Inhibitor Bypass Activity)
 Immune tolerance induction
 Refer to hematologist in specialised centres.

24.  neonatal alloimmune thrombocytopenia
- Thrombocytopenia in < 6 months
 Sepsis and infections ( eg HIV )
 Drug induced thrombocytopenia
 Hematological Malignancy
-eg : Acute leukemia
 Congenital marrow failure syndromes
-eg : Fanconi anemia , thrombocytopenia with absent radius
 Autoimmune disorders
- Eg : SLE , Evan syndrome
 Primary immunodeficiency syndromes
-Wiskott-aldrich syndrome
 Immune thrombocytopenic purpura

25.  Isolated thrombocytopenia with NORMAL blood
counts in a patient, with no clinically apparent
alternative cause of thrombocytopenia .
 In children, ITP is an acute but self limiting that
resolves spontaneously.
Autoantibodies bind to platelet membrane antigen
Increased platelet destruction
Subtypes : 1) Acute ITP
2) Chronic ITP

26.  Usually acute onset.
 Majority will have h/o viral infection in the
preceding 2-4 weeks.
 Can be present as mild cutaneous bleed like
petechiae , to mucosal bleeds like gum
bleeding or epitaxis , to life threathening
bleeds like Intracranial hemorrhage.

27.  Based on history, examination and investigation.
 Physical examination : Absence of
hepatosplenomegaly or lymphadenopathy.
 FBC : Isolated low platelet, normal Hb andTWBC
 FBP : Normal, apart from reduced larger
platelet, no abnormal cells.
 Coagulation profile : prolonged BT, normal PT
and APTT.

28. Usually not require BMA, unless child present with
Atypical features ( eg : Organomegaly, significant
lymphadenopathy, abnormal blood counts or suspicious
FBP. )
 Before starting steroid therapy ( to avoid partially
inducing an undiagnosed acute leukemia)
 If there is failure to respond to Immunoglobulin
therapy
 When there is persistent thrombocytopenia more
than 6 months.
 Thrombocytopenia recurs after initial response to
treatment.

29.  Antinuclear factor and DNA antibodies
 Coomb’s test
 CMV serology ( < 1 yr old )
 Coagulation profile ( suspected NAI and
inherited bleeding disorder)
 HIV testing for those at risk ( eg parents RVD
+ or IVDU )
 Immunoglobulin factor for those with
recurrent infection

30.  Most children remit spontaneously
- 70% achieve platelet count > 50x 109
/L by the end of 3rd
week.
 Careful observation with monitoring of platelet count ,
without specific treatment is appropriate for patient with :
- Platelet count > 20x 109
/L without bleeding
- Platelet count > 30x 109
/L with only cutaneous purpura
- repeat FBC within 7-10 days to ensure there is no evidence
of serious evolving marrow condition.
 Advise precautions with physical activities , avoidance of
contact sports and seeking immediate medical attention if
bleeding occurs should be advised.

31.  Hospitalise the child if
- Severe life threathening bleding eg ICH
regardless of platelet count
- Platelet count < 20x 109
/L with evidence of
bleeding
- Platelet count < 20x 109
/L without bleeding but
inaccessible to health care.
- Parents request due to lack of confidence in home
care.

32. Treatment indicated if
- Life threathening bleeding like ICH
- Platelet count < 20x 109
/L with mucosal bleeding
- Platelet count < 10x 109
/L with any bleeding
Choices of treatment:
i) Oral prednisolone 2mg/kg/day for 14 days
then taper off
ii) Oral prednisolone 4mg/kg/day for 4 days
iii) IVIG 0.8mg/kg/dose for a single dose.

33. Note that the above mentioned regimes do not help to
reduce bleeding complications or mortality or
influence progression to chronic ITP.
S/E of IVIG ( 15-75%) :
- fever, flushing, headache, nausea, aseptic meningitis,
transmission of Hep C ( older preparation )
 Steroid should not be continued if there is no
response or if there is a rapid relapse after withdrawal.
 Treatment should not be directed at increasing the
platelet count above a preset level but rather on the
clinical status of the patient.

34.  Persistent thrombocytopenia after 6 months
of onset ( in 20% )
 Wide spectrum of manifestation:
- Mild asymptomatic low platelet count ->
intermittent relapsing symptomatic
thrombocytopenia -> rare stubborn and
persistent symptomatic and hemorrhagic
disease.

35. Feature Acute ITP Chronic ITP
Peak age Children (2-6 yrs) Adults (20-40 yrs)
Female:male 1:1 3:1
Antecedent Infection Common Rare
Onset of symptoms Abrupt Insidious
Platelet count at
presentation
<20 000 <50 000
Duration 2-6 weeks Long term
Spontaneous remission Common Uncommon

36.  Try to give enough time for the disease to remit
spontaneously.
 EXCLUDE other causes of thrombocytopenia.
 Asymptomatic child – Observe and conservative +
precaution in physical activity
 Symptomatic- short course of treatment like acute
ITP
 Counselling to parents- natural history of disease and
detecting symptoms and complications.
 Parents should be confident in taking care of child
with persistent low platelet count at home.
 Must know when and how to seek early medical
attention.

37.  For child with persistent bleeding.
 MUST d/w paediatric hematologist before
initiating.
 Pulses of steroid :
- Oral dexamethasone 1mg/kg given on 4
consecutive days every 4 weeks for 4 months.
 Intermittent anti-RhD Immunoglobulin
treatment for Rh +ve : 45-50mcg/kg – May
cause drop in Hb level.
 Splenectomy is rarely indicated.

38. Platelet
count
PT APTT Bleedin
g time
Thrombin
time
Additional
test
Hemophilia
A
N N Prolonged N Factor 8 low
Hemophilia
B
N N Prolonged N Factor 9 low
Von
Willebrand’
s disease
N N Prolonged
or
Normal
N VWF /
Factor 8 low
- Impaired
ristocetin
impaired
platelet
aggregation
Liver
disease
Low Prolonged prolonged N
(Rarely
prolonged
)
DIC Low Prolonged prolonged Grossly
prolonged
Oral N Grossly Prolonged N

39.  April 2013
 10 yrs old , Chinese , boy, BW : 30kg
p/w :
1) pain, swelling and reduced movement for both
elbows X 2/7
2) Bruises over bilateral knee
Denies history of recent contact sports.
Denies history of trauma
Denies history of fall.
No other bleeding tendency like epitaxis, gum bleeding,
hemetemesis, hemoptysis, hematuria, malena,
petechiae or bruises at other body part.

40.  He has had multiple previous admissions
since young for joint swellings or soft tissue
injury like calf swelling and bruises.
 Child was previously followed up in Hospital
SultanahAminah since 1 yr old of age.
 Blood investigation during 1 yr old:
- PT 11.9
- APTT 106.6
- FactorVIII <1.0%
- VonWillebrand factor 103.1%

42.  He was diagnosed with Hemophilia A since 1 yr old.
 In 2012, he was referred to HSJ for follow up due to
logistic reason .
 May 2012 : right thigh swelling after a fall
- FactorVIII 750U ( 30U/kg ) x 3 doses
 August 2012:right elbow swelling and bruises after
falling down in basketball court.
- FactorVIII 750U x 15 doses
 September 2012 : bilateral knee bruises after playing
with a friend.
- FactorVIII 750 U x 7 doses
 November 2012: Swelling over elbow . Admitted to
HSAH in SP. FactorVIII given, child was not admitted.

43.  Development history: standard 4 student
with average performance. ( frequent
absence from school due to frequent
admissions)
 Family & Social history:
Father is single parent. Mother is cambodian,
was told to be carrier of hemophilia. Parents
already divorced. He is the only son.

44.  o/e :
Alert, pink , active and comfortable.
Not dyspneic, not tachypneic.
Good perfusion , good pulse volume, CRT < 2 secs.
No petechiae over body. No gum bleeding/nose
bleeding.
Lungs : A/E equal, clear
CVS : DRNM
PA : soft, not distended, no liver / spleen palpable.
Local findings :both elbows slightly swollen and warm
on touch. Restricted ROM : 75-135 degrees bilaterally.
Bruises over both knees. However, bilateral knee has full
ROM.

45.  Ix :
- FBC : Hb 12.8 ,TWC 8.4 , Plt 414
- PT 12.6, APTT 85.5 , INR 1.0
Management:
- Given FactorVIII 750 U BD ( 25mg/kg/dose) for
2 days, followed by 750U OD for 3 days. A
total of 7 doses given.
- Subsequently, child had full ROM in right
elbow, however, his left elbow still slightly
restricted to 15-145 degrees.

46.  TCA stat if hemarthrosis/ soft tissue bleeding
/ bleeding tendency.
 Advise child not to take part in contact
sports.