1) The document outlines a 5-step approach to diagnosing and managing haemophilia: clinical suspicion, laboratory confirmation, counseling, treatment, and education. 2) It describes 3 case studies where haemophilia was correctly or incorrectly diagnosed in infants and children presenting with bleeding. 3) Proper diagnosis requires prompt laboratory testing to identify deficiencies in clotting factors VIII or IX. Treatment involves factor replacement and education of parents on home therapy and preventing joint damage.

1. Approach to Diagnosis &
Management of Haemophilia

2. Step 1: Clinical suspicion

3. Case 1
Baby boy
DOB: 30th
July 2010
SVD, discharged well
That night, noted
bruise behind ears and
scalp swelling
Brought to A&E

4. Case 1 – clinical suspicion
Non-accidental injury (NAI)
Police report made

5. Case 1 – cont’d
Hb 4.5 g/dL
APTT x 3 >100 sec
Rx: PRBCs + FFP transfused

6. Case 1 – factor assay
Sample sent over to haemostasis lab
Within 1 hour
FVIII <1 %
vWF 90%
Δ: Severe haemophilia A

7. Do not mistake haemophilia for non-
accidental injury (NAI)

8. Bleeding – 2 types
1. Immediate bleeding
Defects in primary haemostasis
Vascular abnormality
2. Delayed bleeding
Defects in secondary haemostasis

9. Case 1 – Day 2 of life following SVD
Bleeding in haemophilia is delayed

10. Prompt
Accurate
Step 2: Laboratory confirmation

11. Case 2
2 year old boy
c/o sudden onset of
headache
Vomiting >10x
GCS: 12/15
Suspected posterior
fossa tumour
Courtesy of Dr Peter, March 2012

12. Case 2 – cont’d
Planned for emergency surgery
APTT 127 (36.9- 45.5) sec
Unable to do factor assay
Sample sent over to reference laboratory
Child deteriorated and died
Results came back 10 days later
FVIII < 1%

13. Case 3
5 year-old boy
Admitted for upper GI haemorrhage
h/o recurrent epistaxis and easy bruising
No f/h of bleeding
Hb 4.5 g/dL TW 4.5 Plt 398

14. Case 3 – cont’d
PT 12.o (11.5- 14.4) sec
APTT 102.0 (36.9- 45.5) sec
4 PRBC & 4 FFP transfused
Factor VIII 2.5%
Diagnosis: Moderate Haemophilia A

15. Case 3 – cont’d
Bleeding stopped with FFP x 3 doses
OGDS: pangastritis
Switched to hemofil M (high purity FVIII)
3 days later, re-bled
Hb fell from 11.o to 5.0 g/dL
APTT 98 sec Mixing studies 48 sec

16. Case 3 – cont’d
Suspected inhibitor; switched to PCC
Unable to do inhibitor assay
Sample sent to reference laboratory
FVIII 3% No inhibitor detected
vWF Ag < 1%
Diagnosis: severe type 3 vWD

17. Learn about haemophilia
Genetic risk & Carrier status
Inhibitor risk
Step 3: Counseling

18. Case 1 – Family history
Mom:
2 daughters
(10 and 6 years old)
6 younger siblings
No f/h of haemophilia

19. Case 1 – Family tree
?
NM
I
II
III
6 yrs

20. Case 1 – Counseling
D: Your son has been diagnosed with severe
haemophilia A. Have you heard about haemophilia?
M: No doctor, but from what I see it must be a serious
bleeding disorder
D: Explain about haemophilia

21. Haemophilia
Hereditary bleeding disorder
X-linked
Lack a clotting factor
factor VIII (HA) or factor IX (HB)
Blood fails to clot
Bleeds spontaneously in severe disease
20% present at birth

22. XH X
Carrier Woman Healthy Man
Carrier Girl Healthy Girl Haemophilic Boy Healthy Boy
XH
X
X X X XH Y X Y
Y
Inheritance
50% 50%

23. Classification of Haemophilia
Severity Factor level % Bleeding
Severe < 1 Spontaneous
Moderate 2 – 5 After minor trauma
Mild 6 – 40 After major trauma
or surgery

24. Management
Replace the factor that is missing
Vaccinations are not contraindicated but must be
given S/C
Learn about haemophilia and inhibitor risk
Learn to recognise bleeds
Need to report trauma or bleeding

25. Bruises or haematomas?

26. Avoid aspirin/ NSAIDs
Superficial cuts – OK
Platelets – primary haemostasis

27. IM injections must be avoided

28. Haemarrthrosis
right elbow
Haemarrthrosis – the hallmark of
haemophilia

29. Bleeding in haemophilia
1. Haemarrthrosis
Begin approx age 1 year
Spontaneous
May be preceded by ‘tingling’
Blood fills joint cavity
Rise in pressure is excruciatingly painful
Pressure eventually stops the bleeding
Blood damages cartilage
Joint becomes prone to recurrent bleeds

30. Target joint

31. Joint damage

32. Bleeding in haemophilia
2. Muscle bleeds
Often, apparently spontaneous
May result from exertion
Blood fills muscle capsule or compartment
Compartment syndrome may result
Pressure eventually stops the bleeding
Psoas bleed is a typical example

33. Psoas bleed

34. Muscle contractures

35. Case 1 – Counseling cont’d
M: Does that mean I am a carrier?
D: Possible but in 30% it may be a spontaneous
mutation
M: How do I know if I am a carrier?

36. Ratio <0.7
FVIII 82%
vWF antigen 81%
Ratio: 1.0

37. Genetic testing
Index patient (NM)
Intron 22 inversion by PCR
If negative
Intron 1 inversion
If both negative
DNA sequencing
Once mutation detected, screen mom

38. Case 1 – Result
NM- T1468X mutation
Mom- normal
So mom is not a carrier
Not at risk of having another child with haemophilia
No need to screen daughters and sisters

39. Rx of acute bleeds
Prevention of bleeds – Prophylaxis
Physiotherapy
Step 4: Treatment

40. Case 1 – Intracranial Haemorrhage
Factor replacement
D1 – D2: 100%
D3 – D4: 80%
D5 – D9: 50%
D11 – D14: 30%
Monitor FVIII levels
D1 – post dose, 6 – 8 h later
D2, D4, D6 – trough

41. time (hours)
Factorlevel(%)
0
25
75
100
50
0 362412
24
48
96
60VIII
IX
Factor replacement

42. Factor dosing
Formula:
Dose in units =
weight in kg x % rise in factor required
K factor
(K factor for FVIII = 2.0 , FIX = 1.0)

43. Physiotherapy
Start exercise once
pain subsides
Early restoration of
Full range of motion
Strength
Proprioception,
balance and
coordination

44. Case 1 – Prevention of bleeds
Started prophylaxis age 10
months at 50 IU/kg once a
week
After 4 months, difficulty
with venous access
Port-a-cath inserted on
11/10/11; age 14 months

45. Prophylaxis is the Rx of choice
Many studies
Prophylaxis prevents joint damage
Better joint scores
* Manco-Johnson
Prophylaxis (32 boys) vs. enhanced episodic therapy
(33 boys)
93% vs. 55% (normal MRI joints at 6 years)
Manco-Johnson MJ, NEJM 2007

46. Case 1 – Prophylaxis
Factor VIII replacement for
port-a-cath insertion
100% bolus
50% 8hrly D1- D2
50% 12hrly D3- D5
Followed by prophylaxis 25
iu/kg 3x/wk
Medic alert

47. Prophylaxis dose
Low dose (Utrecht)
15 – 30 IU/kg
High dose (Malmo)
25 – 40 IU/kg
3x/ week for HA
2x/ week for HB
 Principle:

to convert a severe haemophilia to
a moderate haemophilia
Petrini P, Haemophilia 2004
A Srivastava, Haemophilia 2012

48. Starting prophylaxis
Primary prophylaxis before any joint bleeds
Age 1 – 2 years
Primary prophylaxis after 1 or 2 joint bleeds
Damage already done

49. Explain about inhibitor risk
D: There is a 15 – 30% risk of
inhibitor development
P: What is an inhibitor?
D: An inhibitor is an antibody
against the infused factor VIII
P: Why is it important?
D: It will render treatment with
FVIII useless

50. Prophylaxis protects against inhibitor
development
Gouw SC et al. Blood 2007;109(6)4648-4654

51. Self-infusion & Dosing
Recognising problems
Communicating
Step 5: Caregiver & Patient education

52. Mom taught to infuse

53. Starting home therapy

54. Home therapy

55. Self-infusion

56. Home & School Visits

57. Communicate
If any doubts
If bleeding not
resolved
In an emergency
If factors running low
Plan your travels

58. Dental check-ups
½ - 1 yearly
Prevention is better

59. Physiotherapy
Know your exercises
Keep to your
appointments

60. Approach to Diagnosis & Mx of
Haemophilia: 5 steps
Step 1: Clinical suspicion
Step 2: Laboratory confirmation – prompt &
accurate
Step 3: Counseling & carrier detection
Step 4: Treatment/ Home therapy
Step 5: Parent/ Caregiver/ Patient education

61. Thank you
The end