Haemophilia

Definition

• Inherited disorder of intrinsic clotting

Classification

Type	Deficiency	Inheritance	Notes
Haemophilia A	Factor VIII	X-linked recessive. Only males affected, females carriers (1/2 sons are affected, all daughters are carriers, rare homozygous females)	Classic form. Most common cause of severe disease (1:10,000). 30% new mutations. 50% are moderate to severe. 5% have antibodies to Factor VIII, very difficult to treat as infused factor is rapidly destroyed, a contraindication to surgery. Most have near normal life expectancy
Haemophilia B (Christmas disease)	Factor IX	X-linked recessive	Less common (1:50,000). Similar spectrum of activity, identical to Haemophilia A clinically. Treat in same way with Factor IX cryoprecipitate
Von Willebrands disease	VWB factor (VIII-R)	Autosomal dominant	VWB factor carries factor VIII (VIII-C) and facilitates adhesion of platelets to subendothelial collagen. Reduced or dysfunctional VWB factor (abnormal endothelial VWF production or increased endothelial cell VWF proteolysis) diminishes platelet adherence at sites of vascular injury, so bleeding times are prolonged while platelet counts are normal. VIII-C is also ↓, as without VIII-R it is not transported effectively from liver and unbound VIII-C is rapidly catabolised. Treat with cryoprecipitate or DDAVP

Severity depends on the level of clotting factor

Factor level	Bleeding risk
> 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)

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
  • Intraarticular 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 immobilisation
  • 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
    • 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

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
      • Stages 4 & 5
      • Presence of antibodies to Factor VIII (5% of Haemophilia A) is contraindication to elective surgery
      • Avoid pins that penetrate the skin
      • Screen for HIV & Hepatitis B pre op
      • Check Factor VIII levels intraop
      • Meticulous haemostasis
      • Increase Factor VIII levels for MUA & ROS
      • 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

Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 10 October 2026.