Haemophilia

Definition

Inherited disorder of intrinsic clotting

Classification

Haemophilia A
- Classic form
- Deficiency of Factor VIII
- Most common cause of severe disease (1:10,000)
- X-linked recessive
  - Only males
  - Females carriers
  - (1/2 sons are affected, all daughters are carriers, rare homozygous females)
- 30% new mutations
- Severity depends on the level of clotting factor
  - > 50% - normal
  - 25-50% - seldom a problem
  - 5-25% - severe bleed with surgery (Mild)
  - 1-5% - severe bleed with minor injury (Moderate)
  - < 1% - spontaneous bleed (Severe)
- 50% are moderate to severe
- 5% have antibodies to Factor VIII
  - Very difficult to treat
  - Infused factor rapidly destroyed
  - Contraindication to surgery
- Most have near normal life expectancy
Haemophilia B
- Christmas Disease
- Deficiency of Factor IX
- Less common (1:50,000)
- Also X-linked recessive
- Similar spectrum of activity
- Identical to Haemophilia A clinically
- Treat in same way with Factor IX cryoprecipitate
Von Willebrands disease
- VWB factor (VIII-R) functions
  - Carrier for factor VIII (VIII-C)
  - Facilitates adhesion of platelets to subendothelial collagen
- Reduced or dysfunctional VWB factor due to
  - Abnormal endothelial VWF production
  - Increased endothelial cell VWF proteolysis
- Leads to diminished platelet adherence at sites of vascular injury
  - Bleeding times prolonged
  - While platelet counts are normal
- VIII-C is also ↓
  - In absence of VIII-R » VIII-C is not transported effectively from liver
  - Unbound VIII-C rapidly catabolised
- Autosomal Dominant
- Treat with Cryoprecipitate or DDAVP

Epidemiology

Combined incidence of ~ 1/10,000
Manifestations of factor VIII & IX deficiency indistinguishable

Clinical Features

Presentation
- Male with positive family history
  - May present after circumcision
  - First bruising at 3/12
  - Severe bruising at walking age
  - May have spontaneous haemarthroses
    - Knee > Elbow > Ankle
  - Milder forms may present after dental extraction or operative procedure
- Bleeding
- Bruises
- Muscle haematomas
- Haemarthroses
  - May occur some time after the injury as defect in clot formation (1st stage) rather than haemostasis (2nd stage)
  - May be no trauma
- HIV
  - 70% of haemophiliacs who received untreated pooled Factor VIII are HIV positive
  - 90% of severe haemophiliacs HIV positive

Investigations

APTT ↑
PT ↑
Bleeding time normal
Platelet count normal
Low Factor VIII coagulant (VIII-C) activity diagnostic

Treatment

Blood Products
Initially used FFP
- Volume too great
- High levels of factor VIII not achieved
Then cryoprecipitate
- Higher levels Factor VIII
- Exact amount unknown
- Store at very low temperature
Now use heat-treated Factor VIII concentrates
Factor VIII concentrates
- Preparation
  - Initially pooled & untreated Factor VIII
    - High HIV & Hepatitis risk

Now treated
- Detergent & Heat
Activity lower
Available in dried concentrated form
Recombinant Factor VIII being developed

Administration
- 1U/ kg ↑ the Factor VIII by 2%
- Half life of 6-12 hours
- Aim to achieve level of
  - 15% in mild bleed
  - 30% in severe bleed

Repeat in 8 hours
Administration at home possible
Beginning to be used prophylactically

Haemophilic Arthropathy

Haemarthrosis = synovial hypertrophy = more prone to injury
Bleeding » synovitis » bleeding
Recurrent Intraarticular Bleed causes
- Chronic synovitis
- Progressive articular destruction
All severe haemophiliacs have arthropathy by adolescence

Pathology

Joint
- Synovial tissue trapped & nipped in joint
- Haemorrhage into joint leading to
  - Synovitis
  - Synovial fibrosis
  - Haemosiderin accumulation in synovial cells
    - Makes synovium more susceptible to further injury
    - Synoviocytes rupture when iron storage excessive

Intrarticular clots producing fibrous tissue
- Adhesions across joint that tear & bleed
Synovial cavity divided into small loculated spaces

Vascular pannus covers the articular surface & destroys it
Cartilage progressively destroyed by
- Synovial cell death releasing
  - Lysosomal enzymes
  - Iron which interferes with cartilage metabolism (GAG & procollagenase)

Vascular pannus
Prolonged immobilization

Subchondral bone exposed
Subchondral cysts may appear
Osteoporosis due to disuse
Increased blood flow to joint results in epiphyseal overgrowth

Think Haemophilia if see
- Destroyed joint
- Epiphyseal overgrowth
- Lytic bony lesion
Muscle
- Recurrent bleeds lead to fibrosis & contracture
- May result in deformity
- May be complicated by
  - Compressive nerve palsy
  - Compartment syndrome
Cysts
- Massive bleed into muscle (usually thigh)
- Haematoma encapsulated prior to resorption
- Enlarges by osmosis & more bleeds (thus grows rather than resorbed)
- Filled with old degenerative blood products
- May erode through skin or viscus
- Can become abscess
Pseudotumour
- Involves bone
- May occur by
  - Subperiosteal bleed
  - Intraosseous bleed
  - Bleed into muscle with loose periosteal attachment

Subperiosteal form see periosteal stripping & new bone formation
Intraosseous form see ill-defined lesion with extensive osteolysis & some new bone formation
Confuse with
- Sarcoma
- GCT
- ABC
May destroy bone & lead to pathological fracture

Clinical

Joint
- Acute Haemarthrosis
  - Knee > Elbow > Ankle
  - Hip & Shoulder rarely
  - Joint is red, swollen & hot
  - Acutely painful
  - Held in flexion
- Subacute Haemarthrosis
  - After > 2 bleeds
  - Synovium thickened & boggy
  - Moderate restriction of ROM
  - Pain not prominent
- Chronic Haemarthrosis
  - After 6/12
  - Bleeds less frequent & more difficult to detect
  - Joint shows
    - Significant limitation of movement
    - Fibrous contracture
    - Muscle wasting
Muscle
- Most commonly affects affects
  - Iliopsoas
  - Thigh
  - Calf
  - Forearm
- Painful swelling
- Resisted ROM in associated joint
- Iliopsoas bleed can lead to femoral n compression
- Recurrent calf bleeds can lead to equinus contracture of foot
- Forearm bleed can lead to Volkmann’s
Pseudocysts
- Rare
- Involve mainly ilium & the femur

Radiological Classification

Arnold & Hilgartner (1977) Classification of Haemophiliac Arthropathy
Stage	Description
1	Acute haemarthrosis Soft tissue swelling
2	Subacute haemarthrosis Epiphyseal osteoporosis Epiphyseal overgrowth
3	No significant narrowing of joint Squaring of patella Enlarged femoral condyles Widened intercondylar notch in knee Widened trochlear notch at elbow
4	Marked narrowing of joint space
5	Joint destruction Mimics RA / TB

Prevention

Padded crib
Supervision & discourage high risk activities
Activity modification
Prophylaxis (very expensive – not practised in Australia)
- From 1-2yo until late teenage years
- After first joint bleed
- Maintain factor levels > 1%
- 3 weekly factor VIII/ 2 weekly factor IX

Treatment

Acute Haemarthrosis
- Usually treat at home
- Immediate IV dose of Factor VIII
  - To attain levels > 30% (30-50% for 24 hrs)
  - Usually single dose sufficient (30-50U VIII/kg/dose)
  - Pain quickly resolves

Adequate analgesia (not NSAIDS)
For first 24 hours
- Immobilise
- Firm compression
Once bleeding stops
- Ice packs
- Mobilise
Place of aspiration/ wash out controversial
- Reduces pain & swelling
- Removes toxic products of degradation
- May need diagnostic aspiration to rule out infection
- No evidence that decreases risk of arthropathy

Subacute Haemarthropathy
- Further treatment indicated if
  - Failure to respond to above regimen

2 bleeds in short period of time
Initially
- Prednisone for 5/7
- 2-3 doses of Factor VIII for level > 30%
If still not responding then 6-8 week course of
- Factor VIII replacement prophylactically
  - Level > 20%
  - 3x/ week

Active PT
- Quads & ROM

Chronic Haemarthropathy
- Nonoperative
  - 6 months of
    - Small doses of prednisone
    - Prophylactic Factor VIII replacement
    - Active PT
    - ± Inpatient traction to correct FFD
- Operative
  - Synovectomy
    - When non-op treatment fails
    - Not beyond Stage 3
    - Open or arthroscopic
    - Reduces number of bleeds
    - Doesn’t stop cartilage degeneration
  - Corrective Surgery
    - Tendon lengthening
      - Equinus ankle
      - Knee FFD
      - Volkmann’s forearm contractures
    - Osteotomy

Most common deformity is FFD & Valgus knee
Can be corrected with supracondylar osteotomy

Arthrodesis

Not often performed due to multiple joint involvement
Useful for AJ & ST joint

TJR
- Hip & Knee
- Tourniquet
- Strict universal precautions
- Meticulous haemostasis, layered closure
- suction drain
- Avoid excessive diathermy – wounds slough
- Can do multiple joints/ procedures at the one sitting to achieve functional limb
- Compared with non-haemophiliacs
  - incidence of periop complications
    - Bleed & Infection
  - failure rate
    - 50% at 10 years

Maintain Factor VIII levels at
- 100-120% for 2 days
- 80-100% for 2 weeks
- 30-50% for 6 weeks

Muscle Bleed
- Immobilise for longer to prevent further bleed
- Initially splint in position of comfort
- Then when bleed ceased serial splint to functional position
- May require splintage for nerve palsy as well
Life-threatening spinal or cerebral bleed
- Minimum of 100% factor VIII 6 weeks

Health Quality Initiative by

Western Hospital

Sunshine Hospital

Williamstown Hospital

Haemophilia

Definition

Classification

Epidemiology

Clinical Features

Investigations

Treatment

Haemophilic Arthropathy

Pathology

Clinical

Radiological Classification

Prevention

Treatment