Definition
Hereditary bleeding disorder due to defective and/or deficient factor VIII molecule
Inherited X-linked recessive disorder
- occurs almost solely in males
- female carriers usually asymptomatic
- 30% have no family history
Haemophilia A
FVIII deficiency
X-linked disorder
- 1:10 000
- all ethnic groups
- all parts of the world
Reduction in circulating levels of functional FVIII
- decreased amount or defective FVIII
- carriers have 50% of normal levels
- bleeding problem if <5%
FVIII complex protein with 2 forms
- small molecule with coagulant activity (VIII:C)
- larger molecule which circulates with von Willebrand factor (VIII:vWF)
Haemophilia B / Christmas Disease
FIX deficiency
Also X linked recessive
- less common
- 1:30 000
Similar spectrum of disease
- identical to haemophilia clinically
- treat with Factor IX cryoprecipitate
Pathogenesis
Intrinsic pathway
Factor VIII
- an essential cofactor for factor IXa
- catalyses conversion of factor X => Xa
- in the presence of activated factor VIII the rate of factor Xa production is dramatically increased
Without factor VIII activity
- delayed clot formation
- excessive bleeding and poor wound healing
Clinical Features
Orthopaedic Manifestations
1. Haematomas
2. Haemarthrosis
3. Bone cysts and pseudotumours
Depend on level of FVIII
<1%
- frequent spontaneous bleeding in early life (haemarthroses)
<5%
- severe bleeding following injury
>5%
- milder disease post-traumatic bleeding only
Most frequent cause of death is AIDS (transmitted in 1980s)
1. Haematomas
Haemorrhage into subcutaneous connective tissue or into muscle
- with or without trauma
- superficial or deep
Problems
- expand locally to compress organs, vessels, nerves
- expand distally to retro-peritoneal / retro-pharyngeal
- may cause compartment syndromes
Can lead to muscle contractures / atrophy & nerve palsies
- volkmann forearm contractures
- iliopsoas haematoma and femoral nerve palsy
- recurrent calf bleeds and equinus
2. Haemarthroses
Acute
- rapid tense swollen red tender articulation
- painful and stiff
- fever and leukocytosis
- symptoms decrease quickly
Subacute
- after 2 or more haemarthroses
- complete recovery of joint not evident
- peri-articular swelling secondary to boggy synovium
- joint motion is restricted
- contractures evident
- muscle atrophy
Chronic
- after subacute present for 6-12 months
- severe and persistent contractures
- final stage fibrotic contracted and destroyed articulation
3. Bone cysts and Pseudotumors
3 types
1. Simple cyst
- confined within fascial envelope of muscle
2. Cyst in soft tissues
- interferes with blood supply of adjacent bone and periosteum
- resorption of bone and cyst formation
3. Result of sub-periosteal bleeding
- resultant stripping limited by aponeurotic or tendinous attachments
As cyst increases
- compresses and destroys muscles, nerve and bone
- likely to reform unless completely removed
- tend to become multi-loculated
- erodes through tissues into viscera and skin
- predisposed to infection
- difficult to differentiate from malignant tumours
- needle biopsy with caution
Differential Diagnosis
- primary and secondary neoplasms
- infection
Also
AVN
- epiphyseal fragmentation and collapse
- especially hip and ankle
- secondary to intra-osseous bleeding or intracapsular bleeding
- causes increased intra-articular pressure, vascular occlusion and subsequent osteonecrosis
Ectopic Ossification
- occurs in peri-articular tissues
Fractures
- fracture healing normal
- pseudotumours may develop at site of fracture
Chondrocalcinosis
- haemosiderin alters articular mechanics that leads to cartilage calcification
Pathology
- blackish fluid containing clots within recesses of articular cavity
- embedded within synovial membrane or adherent to capsule
- with each bleed resorption less
Synovium
- discolouration of synovial membrane secondary to haemosiderin absorption
- hypertrophy, hyperplasia and increased vascularity
- synovial villi more numerous
- synovial tissue and adjacent capsule/soft tissues undergoes fibrous proliferation
- appears similar to inflammatory pannus
Cartilage
- becomes discoloured
- reveals focal areas of fibrillation, erosion, necrosis
- may expose sub-chondral bone
- modified in several ways
- loss of subchondral bone plate (therefore calcified cartilage rests on cancellous bone)
- trabecular thinning and resorption (enlarged marrow spaces which appear cystic)
- granulation tissue extends from bone into overlying cartilage
Sub-chondral cysts
- represent sites of intra-osseous haemorrhage
- cysts common beneath sites of abnormal cartilage
Periosteal bleeding (pseudo-tumours)
- can lead to secondary periosteal bone formation
- creates irregular and expanding bony contours
Immature skeleton
- chronic hyperaemia of epiphyseal cartilage
- leads to accelerated maturation and enlargement of epiphyses
Investigations
Platelet count / Bleeding time normal
APTT increased
PT Normal
Low factor VIII: C Activity
X-rays
Think Haemophilia if destroyed joint & epiphyseal overgrowth + lytic bony lesion
Affects hinge joints
1. Knee
Widened femoral condyles and intercondylar notch
- distal condylar surface may appear flattened
- squaring of the inferior pole of patella
- subluxation patella and particularly postero-lateral tibia on femur
NB
- not specific for haemophilia
- many of changes similar to those seen in juvenile chronic arthritis
2. Elbow
3. Ankle
Arnold Classification Arthropathy
Stage I
- soft tissue swelling + effusion
- periarticular osteoporosis
Stage II
- overgrowth / widening of epiphysis
- surface irregularity / small erosions
- joint space maintained
Stage III
- some narrowing of joint space
- extensive bony erosions
- sub-chondral cysts
Stage IV
- cartilage destruction
DDx
Trauma
Juvenile onset RA
PVNS
Infection
Other coagulation disorder
Prognosis
Patients treated after 1985 can expect to have normal life spans
- older patients had high incidence of AIDS
- now recombinant
Management
Non Operative Management
Factor VIII
Replacement of missing / defective component
Factor VIII concentrate
- initially pooled / high risk of HIV
- then heat treated to eliminate this risk
- now produced by recombinant technology
FVIII
- has a half life of 12 hours
- 1 u/kg increases VIII by 2%
- given tds
Aim
- 15% for mild bleed
- 30% for severe bleed ~ 1000u tds
- give ASAP at home
Problem
- 10% will develop antibodies
- IgG inhibitor
- use FVII in life threatening emergency
Other options
- FFP: concentrations of FVIII too dilute
- DDAVP produces a rise in FVIII proportional to initial level
Acute Haemarthrosis
Usually managed at home
- IV F VIII 1000U tds if 70kg
- analgesia (Not NSAID)
- splint & compression first 24 hours
- once bleeding stops ice packs & mobilise
Place of washout controversial
- reduces pain & swelling
- no evidence that it decreases risk of arthropathy
Subacute Haemophilia arthropathy
Treatment
1. Prednisone 5 days
- 2-3 doses FVIII for level > 30%
- physiotherapy
2. Prednisone 6 weeks
- FVIII > 20% 3 x week
- physiotherapy
Operative Management
Indications
- synovectomy
- contractures
- OA hip / knee / elbow / ankle
Perioperative Management
F VIII
Levels
- 100% pre and post op
- > 60% for 2/52
- 30% for 6/52
Haematologist
- close working relationship with surgeon
- adequate reserves of concentrate available in advance
- lab available to perform unlimited assays for the factor
- identify antibody/inhibitor production
- screen for HIV / HBV / HCV
FVIII inhibitor
Increasing problem
- new techniques involving FEIBA
- factor eight inhibitor bypassing activity
Lauroua et al Haemophilia 2009
- FEIBA in 12 patients having major and minor operations
- successful bleeding control
Operative technique
As many procedures at one sitting as the patient can take
- monitor factor VIII intra-operatively
- pneumatic tourniquets
- tight careful wound closure to avoid dead space
- avoidance of diathermy (coagulated areas slough after surgery)
- wound suction to deep wounds minimum 24 hours
- no aspirin platelet inhibitors post operatively
- no intramuscular injections
Post-operatively
- Need F VIII for MUA and ROS
Synovectomy
Indication
Chronic synovitis
- stage 1 or 2
- reduces incidence of bleeding & improves function
- slows progression of disease but doesn't prevent
Results
Rodriguez-Merchan Int Orthop
- 27 surgical synovectomies of the knee
- average age 13
- better results in arthroscopic than open
- reduces incidence of hemarthrosis and improve ROM
- effects diminish with time
- disease progresses, but likely more slowly
Patti et al Arthroscopy 1996
- arthroscopic synovectomy in 9 ankles
- reducing bleeding incidence and improved ROM and function
Contractures
1. Fixed ankle equinus
- T Achilles equinus
2. FFD and valgus knee
- supracondylar osteotomy
Arthrodesis
AKJ / STJ
Knee Arthroplasty
Results
- good functional results
- good long term survival
- higher rates of infection
Rodriguez-Merchan JBJS Br 2007
- 35 TKR followed up for average 7.5 years
- average patient age 31
- 97% survival at 7.5%
- 94% good or excellent results
- 1 deep infection requiring 2 stage revision
- 1 patient required embolisation
Silva et al JBJS Am 2005
- 90 TKR in hemophilia
- rate of infection was 16%
- 12 required removal, 9 for late infection
- knee society scores good or excellent in 97%
Hip Arthroplasty
Kelley et al JBJS Am 2005
- 34 patients average age 38 followed up for 8 years
- 3 late deep infections
- 21% rate of aseptic loosening
Elbow
Chapman-Sheath et al JBJS Br
- TER in 7 elbows
- one deep infection
- excellent functional results at 4 year follow up