Hemophilia

- 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