· combined incidence is 1 in 10 000 male births
· classic haemophilia
· deficiency of factor VIII
· most common of severe disorders
· X-linked recessive inheritance
· only affects males
· carried by females
· 30% are new mutations (very high cf. other inherited diseases)
· severity varies depending on level of clotting factor
· > 50% - normal
· 25-50% - seldom have problems
· 5-25 % - severe bleeding with operations (mild)
· 1-5 % - severe bleeding after minor injury (moderate)
· <1% - spontaneous bleeding (severe)
· 50% of known haemophiliacs are moderate or severe
· 5% of patients develop antibodies to factor VIII
· very difficult to treat
· infused factors destroyed
· deficiency of factor IX
· less common
· also X-linked recessive inheritance
· similar spectrum of severity
· deficiency of von Willebrand factor
· of von Willebrand portion (VIIIR)
· autosomal dominant inheritance
· male with positive family history
· may present after circumcision
· otherwise first bruising appears at 3-4 months
· severe bruising at walking age
· may be spontaneous haemarthroses
· milder forms may present after dental extraction or operative procedure
· in the form of
· bruises
· muscle haematomas
· haemarthroses
· may occur some time after injury
· defect is in clot formation (2nd phase) rather than haemostasis (1st phase)
· may be no known trauma
· 70% of haemophiliacs who have received pooled untreated factor VIIII preparations are HIV positive
· 90% of severe haemophiliacs are HIV positive
· platelet count and bleeding time normal
· APTT prolonged and PT normal
· low factor VIII coagulant activity diagnostic
· initially fresh frozen plasma used
· volume too great
· high levels could not be achieved
· then cryoprecipitate used
· contains higher level of factor VIII
· exact amount in transfusion not known
· must be stored at very low temperatures
· then factor VIII concentrates developed
Preparation
· initial factor VIII concentrates were untreated pooled plasma products
· high risk of HIV and hepatitis transmission
· now blood products treated to reduce risk
· heat or detergent
· factor VIII activity lower
· available in convenient dried concentrate form
· reconstituted and infused when needed
· recombinant factor VIII being developed
Administration
· 1 U/kg elevates VIII by 2%
· half-life is 6-12 hrs
· aim to achieve level of
· 15% for mild bleed
· 30% for severe bleed
· repeat every 8 hrs
· can be administered at home
· allows administration as soon as possible after bleed occurs
· beginning to be used prophylactically
· recurrent intra-articular bleeding can cause
· chronic synovitis
· progressive articular destruction
· all haemophiliacs with severe disease have arthropathy by adolescence
· starts when synovial vessel trapped and nipped in joint
· haemorrhage into joint causes
· synovial inflammation
· subsynovial fibrosis
· haemosiderin accumulation in synovial cells
· resulting synovial inflammation makes synovium more susceptible to further nips
· intra-articular clots organise and form fibrous tissue
· adhesions form across joint which may tear and bleed
· synovial cavity divided into small loculated spaces
· synoviocytes rupture when excessive iron absorbed
· cartilage gradually eroded due to liberation of lysosomal enzymes
· vascular pannus covers articular surface and further destroys it
· subchondral bone exposed
· subchondral cysts may appear
· osteoporosis develops due to disuse
· increased blood flow to joint leads to epiphyseal overgrowth
· recurrent bleeds lead to fibrosis and contracture
· may result in deformity
· may be complicated by
· compressive nerve palsy
· compartment syndrome
Cyst
· from massive bleed into muscle
· haematoma encapsulated before it is resorbed
· may draw in more fluid by osmosis
· cyst thus grows rather than resolves
· further acute bleeding may occur into cyst
· filled with tarry degenerative products of blood
· may erode through skin or viscus and become an abscess
Pseudotumour
· involves bone
· may occur by
· subperiosteal bleed
· intraosseous bleed
· bleeding into muscle with wide periosteal attachment
· subperiosteal form shows periosteal stripping and new bone formation
· intraosseous form appears as ill-defined lesion with extensive osteolysis and some new bone formation
· may be confused with
· sarcoma
· giant cell tumour
· aneurysmal bone cyst
· may destroy bone and lead to pathological fracture
Acute haemarthrosis
· most commonly affects
· knee
· elbow
· ankle
· hip and shoulder (occas.)
· joint is
· hot red and swollen
· acutely painful
· held in flexion
Subacute haemarthrosis
· after 2 or more acute bleeds
· synovium is thickened and boggy
· moderate restriction of ROM
· pain not prominent
Chronic disease
· after subacute form present for 6 mths or more
· bleeds less frequent and more difficult to detect
· joint shows
· significant limitation of movement
· fibrous contracture
· deformity
· muscle wasting
· most commonly affects
· iliopsoas
· thigh
· calf
· forearm
· painful swelling appears
· movement of related joint resisted
· iliopsoas bleed can compress femoral nerve
· recurrent calf bleeds can lead to equinus deformity
· forearm bleed may lead to Volkmann’s contracture
· rare
· most common around femur and ilium
· progressive destruction
· stages described
Stage 1
· after acute haemarthrosis
· soft tissue swelling
Stage 2
· subacute haemarthropathy
· epiphyseal osteoporosis
· epiphyseal overgrowth
Stage 3
· no significant narrowing of joint
· squaring off of patella
· widened intercondylar notch in knee and trochlear notch in elbow
Stage 4
· marked narrowing of joint space
Stage 5
· joint disintegration
· usually treated at home
· immediate intravenous dose of factor VIII
· to achieve level above 30%
· usually single dose sufficient
· pain resolves quickly
· adequate analgesia (not aspirin or NSAIDs)
· for first 24 hrs
· immobilise limb in splint
· apply firm compression
· once bleeding stops
· ice packs
· mobilisation
· place of aspiration or washout controversial
· reduces pain and swelling
· removes blood and thus reduces requirement for degradation with possible toxic effects
· no evidence that it decreases risk of arthropathy
· requires admission to hospital
· may require diagnostic aspiration to rule out infection
· further treatment indicated if
· failure to respond to above treatment
· two or three bleeds in short period of time
· initially
· prednisone 5 days
· 2 or 3 doses of factor VIII for level > 30%
· if still not settled, 6-8 wk course of
· prophylactic factor replacement (level > 20% 3x / wk)
· active physiotherapy (graduated quads and ROM)
Nonoperative
· in form of 6 months of
· small dose of prednisone
· prophylactic factor replacement
· active physiotherapy
· inpatient traction may be used to correct flexion deformity
Synovectomy
· when nonoperative treatment fails
· not indicated beyond stage 3
· open or arthroscopic
· reduces number of bleeds
· does not slow cartilage degeneration
Corrective surgery
· for stage 4 and 5
· presence of antibodies is contraindication to elective surgery
· avoid pins that penetrate skin
· screen for HIV and hepatitis B preoperatively
· check factor levels intraoperatively
· meticulous haemostasis
· increase factor levels for procedures such as MUA and ROS
Osteotomy
· most common deformity is flexion contracture with valgus of knee
· can be corrected with supracondylar osteotomy
Arthrodesis
· not often indicated because multiple joints involved
· useful for ankle and subtalar joints
Total joint replacement
· of hip and knee
· cf. nonhaemophiliacs
· similar procedure
· higher perioperative complication rate (esp. haematoma and infection)
· only 50% survival at 10 yrs
· maintain factor VIII levels at
· 100-130% for 2 days
· 50-60% for 2 wks
· 30-50% for 6 wks
Tendon lengthening
of tendo Achilles for equinus deformity
· need to immobilise for longer period
· to prevent further haemorrhage
· initially in position of comfort
· when bleeding ceased, serial correction of position until functional position achieved
· associated nerve palsy may require splintage