Hemophilia is a genetic bleeding disorder caused by deficiencies in clotting factors VIII or IX. It is inherited in an X-linked recessive pattern and primarily affects males. Symptoms range from easy bruising to spontaneous internal bleeding that can be life-threatening. Treatment involves replacement of the missing clotting factor through infusions to prevent or treat bleeding episodes. Repeated bleeding can lead to chronic joint damage over time without proper management.

1. Hemophilia
Dr. Kalpana Malla
MD Pediatrics
Manipal Teaching Hospital
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2. Introduction:HAEMOPHILIA
• Commonest inherited bleeding
disorder
• Bleeding due to deficiency of FVIII /
IX / XI coagulant activity
• Severity of bleeding is related to
FVIII / IX /XI concentration in blood

3. INCIDENCE
• 1 per 5,000 male births
• 1 per 10,000 population
• 85 % - F VIII deficiency
• 10- 15 % - F IX deficiency
• Haemophilia A: B= 7:1

4. Mode of Inheritance :
– X- linked recessive
Males affected
Females carriers

5. INHERITANCE

6. INHERITANCE
• Father with Haemophilia:
Daughters are carriers Sons normal
• Mother with haemophilia gene (carrier)
Sons 50:50 normal or affected
Daughters 50:50 normal or carriers

7. FEMALES AFFECTED ONLY WHEN:
1) TURNERS SYNDROME
2) MOSAICISM/LYONISATION
3) MOTHER TO DAUGHTER
TRANSMISSION (POSSIBLE
THEORETICALLY BUT EXTREMLY
RARE)

8. Types:
• Haemophilia A – deficiency of Factor VIII
• Haemophilia B – deficiency of Factor IX
• Haemophilia C – deficiency of Factor XI

9. HAEMOPHILIA A & B:
• Basic abnormality :
1. Reduction in amount of protein in
factor
2. Dysfunctional protein
5-10 % Haemophilia A
40-50 % ” ” B

10. Severity of haemophilia
• 1 ml of normal plasma contains 1 unit (U) of each
factor
100 ml plasma contains 100 U/dl (100 % activity)
Severity depends on factor level in blood:
● Severe haemophilia: < 1 U/dl (%)
● Moderate haemophilia: 1-5 U/dl (%)
● Mild haemophilia: 5-30 U/dl (%)

11. Severity of haemophilia
• Haemostatic level of factor VIII: 30-40 U/dl
• ” ” of factor IX: 25-30 U/dl

12. Severity of Haemophilia
Severity Factor Type of presentation
level
iu/dl (%)
Severe <1 Spontaneous bleeds, Severe bleeding
Moderate 1-5 Few bleeds, Haemathrosis - traumatic
Mild 5-30 Few bleeds, Post-traumatic
Post-dental surgery

13. Pathophysiology:
tissue injury
platelet plug
delayed (Haemophilia A & B)
fibrin clot
prolonged bleeding

14. CLINICAL FEATURES – SUBTLE
• Bleeding as a baby rare
• Prolonged bleed from umbilical cord
• Muscle hematoma during immunisation
• Bleeding during circumcision

15. CLINICAL FEATURES – SUBTLE
• Toddlers - Large and prolonged bleed to
trivial injury/cuts/abrasions
• Lip bleeds (hematomas)
• First bleeding in childhood
Tooth extraction
Trauma with walking
Gum bleeds while brushing teeth

16. SIGNIFICANT HEMORRHAGES
• RETROPERITONEAL H’GE: severe abd
pain, anemia and shock
• HEMATURIA
• GI BLEED : difficult to control, severe
• INTRACRANIAL:
extradural, subdural, intracerebral
- Headache, vomiting, altered sensorium ->
coma
• May be seen in neonates

17. SUBDURAL HEMORRHAGE

18. CLINICAL FEATURES - FRANK
HEMARTHROSIS (joint bleed) – hallmark of
hemophilia
• Joints affected:
• in toddlers - ankle (most common) – earliest jt
involved due to lack of stability as they assume
upright posture
• Older child – knee, elbow (most common)
** Target joint – recurrent bleeding at a same
joint
• LL > UL

19. CLINICAL FEATURES - FRANK
• Later : all joints
• Contact sports can provoke
• Recurrent – may be unprovoked,
spontaneous
LARGE HEMATOMAS & EXTENSIVE
ECCHYMOSES

20. BLEEDING INTO JOINTS
• First haemorrhage : Swelling >> Pain
• Subsequent haemorrhages: Pain >>
Swelling

21. Bleeding in Haemophilia
• Acute Haemarthrosis
• Chronic haemophilic arthropathy
• Bleeding into muscles
• Haemophilic pseudo tumour - cysts
• Haematuria
• Gastrointestinal bleeding
• Intracranial bleeding

22. Bleeding in Haemophilia
BLEEDING IN CARRIERS
• Reduced FVIII (IX) levels
• Mild bleeding tendency
• Childbirth

23. C/F OF ACUTE HAEMARTHROSIS
• Abnormal sensation
• Pain and swelling of joint
• Limitation of movement - especially
flexion
• Tenderness and heat in the joint
Acute symptoms last 3-4 days; full recovery
takes weeks

24. STAGES
• Initial bleed into joint - haemarthrosis
• Inflammatory stage affecting
Synovium (synovial hypertrophy)
Cartilage - Bone
• Final Stage
Permanent joint changes
Erosion & destruction Cartilage, Bone -
Knees** ,Ankles** , Elbows*
Wrists
Shoulders less common
Hips

25. Chronic Haemophilic Arthropathy
• Repeated bleeds - many years 
Chronic degenerative changes
• Chronic haemophilic arthritis → Loss
of joint movement → Fixed flexion
contractures → Severe muscle wasting
→ Muscle action imbalance →Valgus
deformities → Crippling deformities →
Wheel chair-bound

26. Chronic Haemophilic Arthropathy – Radiological
Changes
• Epiphyseal overgrowth
• Enlargement of bone ends
• Loss of cartilage (joint space)
• Gross irregularity articular surface
–Subchondral collapse
–Subchondral cysts
–Osteophyte formation
–Osteoporosis
–Changes in joint alignment

27. HAEMOPHILIC PSEUDO TUMOURS (BLOOD
CYSTS)
• Cysts within the fascial muscle envelope
• Cysts arising in muscles
• Cysts arising from sub-periosteal
haemorrhage
• Pseudo tumours in bone
• Gross destruction of normal architecture
of bone
• Large bone cysts
• Pathological fracture

28. Complications :
• Pain
• Anaemia (proportionate to bleeding)
• Constitutional disturbances:
fever < 24 hrs
anorexia, malaise
• Chronic arthritis
• Pressure effects of large haematomas
• Transfusion acquired infections
• Inhibitors

29. Lab findings:
• Hb low – proportional to blood loss
• Platelets- normal
• Bleeding time -normal
• PT normal
• APTT prolonged > 2-3 times ULN
• CT prolonged
• Low levels of F VIII / IX
• Factor VIII and IX assay : mixing studies
• Genetic analysis

30. MIXING STUDIES
• To determine if prolonged PT or PTT is due to
a factor deficiency or an inhibitor
• Normal plasma : all Clotting factors-V,VIII,
IX,X,XI,XII
• Method: add patient plasma to equal volume
of normal plasma and repeat PT & PTT
• Correction of PT & PTT – suggests- deficiency
of clotting factors
• Assays for factors

31. MIXING STUDIES
• Remains prolonged after mixing study:
indicates inhibitor - most common is
lupus anticoagulant
- therapeutic anticoagulant
- rarely ,inhibitors to factors VIII, IX, XI

32. MIXING STUDIES
• With normal /adsorbed plasma/aged plasma
• Normal plasma : all factor present
• Adsorbed plasma : FIX- deficient
• Aged plasma - FVIII- deficient
• Mix patient’s plasma with normal /aged/
adsorbed plasma –
• Correction of APTT with normal & aged
plasma/ not with adsorbed plasma  F IX
deficiency

33. • Correction of APTT with normal /
adsorbed plasma & not with aged
plasma  F VIII deficiency
• If correction does not occur suspect
inhibitor

34. Inhibitors:
• Antibodies against factors blocks clotting
activity
• 14-25 % patients who receive factors (VIII/ IX)
• Failure of a bleeding episode to respond to
appropriate replacement therapy 1st sign of
inhibitor
• Others develop higher titres 
desensitisation- higher doses of factors given

35. RADIOLOGICAL INVESTIGATIONS
• Radiographs of joints
• USG joints for effusions
• MRI joints/ abdomen
• CT head

37. MANAGEMENT -PRINICIPLES
• Control bleeding episodes – replacement
therapy
• Prophylaxis and prevention
• Life style modifications
• Treatment of complications
• Rehabilitation
• Antenatal diagnosis and counselling
• Team effort : pediatrician, hematologist,
orthopedician, physiotherapist, dentist

38. REPLACEMENT THERAPY
• Fresh whole blood
• FFP
• Cryoprecipitate
• Factor concentrates
• Recombinant/ porcine factor VIII FIX :
inhibitors of natural F-VIII/IX
• Prothrombin complex concentrates
(PCC)

39. FFP AND CRYOPPT
• FFP contains F VIII and IX
• CRYOPPT contains F-VIII, fibrinogen, VWF
• 1 unit FFP = 200 units factor VIII/IX
• 1 unit cryoppt = 100 units factor VIII
• FVIII 1u/kg Increase plasma factor VIII by 2% (
2 iu/dl) - t ½ = 8 hrs
• FIX 1u/kg Increase plasma factor IX by 1%
(1iu/dl) - t ½ = 18-20 hrs
• Risk of HIV, HBV, HCV, CMV transmission

40. FACTOR CONCENTRATES
• Prothrombin complex concentrates
(PCC) - Contain F IX & Vitamin K
dependent factors I.e. II, VII, IX, X – high
cost
• Pure factor IX concentrates available
– Currently high cost

41. THERAPY FOR HAEMOPHILIA
• FACTOR RECOVERY AFTER I.V.
INFUSION
Factor VIII 100%
Factor IX30-50%
• Raise factor levels to:
100 U/dl – life threatening bleeds
35- 40 U/dl – other bleeds

42. DOSAGE CALCULATION
• Dose of F VIII (U):
desired rise in plasma F VIII (U/dl) X body wt (kg) X
0.5
• Dose of F IX (U):
desired rise in plasma F IX (U/dl) X body wt (kg) X
1.4

43. Factor
FVIII
level FIX Dose
Indication or Site of Bleeding Dose,
Desired, IU/kg
IU/kg*
%
Severe epistaxis; mouth, lip,
20-50 10-25 20-50
tongue, or dental work
Joint (hip or groin) - Repeat in 24-
48 h 40 20 40
Soft tissue or muscle 20-40 10-20 40
Muscle (calf and forearm) 30-40 15-20 40
Muscle deep (thigh, hip, iliopsoas)
40-60 20-30 40-60
Transfuse, repeat at 24 h
Neck or throat 50-80 25-40 50-80

44. Hematuria 40 20 40
Laceration 40 20 40
GI or retroperitoneal
60-80 30-40 60-80
bleeding
Head trauma (no evidence of
50 25 50
CNS bleeding)
Head trauma (probable or
definite CNS bleeding, eg,
100 50 100
headache, vomiting,
neurologic signs)
Trauma with bleeding,
80-100 50 100
surgery†

45. Other measures:
• General supportive measures:
bed rest
hospitalize for severe bleeds
analgesics
Local haemostasis
Immobilisation
Physiotherapy

46. HEMARTHOSIS MANAGEMENT
• 25 U F-VIII/kg q12h
• Prompt rx : prevent early sequalae
• Check APTT
• Joint immobilisation - 48hrs
• Early ambulation and physio
• NSAIDS : Aspirin, indomethacin – with
caution- may induce GI bleed
• Paracetamol, pethidine, diazepam – can be
used
• Home infusions : train for early administration

47. PROPHYLAXIS
• Mild/moderate hemophilia
• 10-20 units/kg 2-3 times/week
• Can have normal life and
participate in sports

48. PREVENTION
• Immunisation : SC not IM
• Avoid IM injections-
apply pressure 5 minutes
• Avoid contact sports

49. PREVENTION
• Orthopaedic care- traction, splinting,
reconstructive surgery
• Regular dental exam and hygiene
• Prophylactic immunization- hep B
• Counselling

50. DRUGS
• EACA - aminocaproic acid
• Tranexemic acid: 25mg/kg/day
• C/I in hematuria- ppt renal failure
• Desmopressin acetate: increases levels for
first 2 days from body stores
• Danazol
• Fibrin glue : tooth extraction

51. Other agents used:
• Tranexamic acid
Used for external bleeding
eg. teeth extraction
Not for internal bleedings
Inhibits fibrinolysis
decreases F VIII requirement

52. • DDAVP D-amino D-arginine Vasopressin
Found to raise FVIII levels
Mild haemophilia- releases F VIII from storage
sites
Moderate to severe cases- no endogenous
stores treatment ineffective
Mild von Willebrand’s disease
Not effective in Haemophilia B

53. • Danazol:
Androgen
Elevates levels of protein in factors
Increases levels of F VIII & F IX
• Prednisolone
Acute synovitis

54. ANTENATAL DIAGNOSIS
• 18-20 weeks
• Male fetuses
• Fetal blood :
• Amniotic fluid fibroblasts :DNA probe
• Chorionic villous sampling :PCR

55. CARRIER DETECTION
• FVIII-C: FVIIIAg = 1:1 normally
• In carriers FVIII-C is low
• Hence ratio: 0.6:1

56. ACQUIRED HEMOPHILIA
• 5-20% of hemophiliacs develop antibodies against
factor VIII/IX with time - alloantibodies
• Hemophilia A > Hemophilia B
• Suspect when failure of therapy
• Manage:
1) porcine FVIII
2) activated prothrombin complex
3) activated FVII
4) plasmapheresis
5) immunosuppresants
6) recombinant FVIII/IX

57. THERAPY FOR HAEMOPHILIA
• DEMAND THERAPY Hospital
Home
Long standing approach to haemophilia
Patient treats when bleeds
Arrest acute bleed
No arrest, long term sequelae
• PROPHYLACTIC THERAPY

58. PROPHYLACTIC THERAPY
• Initiated with the 1st bleed
• Home - self or patient infused
• Small dose FVIII (FIX) 2-3 X /week ( 20%-
30%)
Prevents bleeds
Prevents long term sequelae
THERAPY FOR SURGERY/ DENTISTRY
• Prophylactic
• Enables major procedures - 10 days cover

59. Thank you
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Medical Post [ www.themedicalpost.net ]