High Yield Overview

Hemophilia: Orthopaedic

Clotting Factor Deficiency and Joint Disease

Factor VIII (85%)Hemophilia A

Factor IX (15%)Hemophilia B

X-linked recessiveInheritance

Knee, ankle, elbowTarget joints

Hemophilia Classification

Hemophilia A

PatternFactor VIII deficiency (85%)

TreatmentFactor VIII replacement

Hemophilia B

PatternFactor IX deficiency (15%)

TreatmentFactor IX replacement

Mild (5-40%)

PatternBleeding after trauma/surgery

TreatmentOn-demand treatment

Moderate (1-5%)

PatternOccasional spontaneous bleeds

TreatmentProphylaxis or on-demand

Severe (under 1%)

PatternFrequent spontaneous bleeds

TreatmentRegular prophylaxis essential

Critical Must-Knows

Hemophilia A: Factor VIII deficiency - most common (85% of cases)
Hemophilia B: Factor IX deficiency (Christmas disease, 15%)
Hemophilic Arthropathy: Iron from blood causes synovitis leading to progressive cartilage destruction
Prophylaxis: Regular factor replacement prevents joint disease - standard of care
Target Joints: Knee (most common), ankle, elbow - hinge joints more affected
Perioperative: Raise factor to 100% pre-op, maintain 50-80% post-op, check inhibitor status

Examiner's Pearls

"
Factor VIII = Hemophilia A
"
X-linked recessive inheritance
"
Iron toxicity causes arthropathy
"
Prophylaxis prevents joint disease
"
Check inhibitor status preoperatively

Clinical Imaging

Imaging Gallery

hemophilia imaging 1 — Clinical imaging for hemophiliaCredit: Rodriguez-Merchan EC, Valentino LA via J Blood Med via Open-i (NIH) (CC-BY)

hemophilia imaging 2 — Clinical imaging for hemophiliaCredit: Rodriguez-Merchan EC, Valentino LA via J Blood Med via Open-i (NIH) (CC-BY)

hemophilia imaging 3 — Clinical imaging for hemophiliaCredit: PMC3307435 via Open-i (NIH) via Open-i (NIH) (CC-BY)

hemophilia imaging 4 — Clinical imaging for hemophiliaCredit: Rodriguez-Merchan EC, Valentino LA via J Blood Med via Open-i (NIH) (CC-BY)

Critical Exam Point: Perioperative Factor Management

Orthopaedic surgery in hemophilia requires meticulous factor replacement:

Pre-operative: Raise factor level to 100%
Post-operative: Maintain at 50-80% for 7-14 days depending on procedure
Coordinate with haematology - essential for all procedures
Check inhibitor status (Bethesda assay) - affects treatment strategy
Inhibitors present: May need bypassing agents (FEIBA, rFVIIa)

Mnemonics for Exam Recall

Mnemonic

Hemophilia Types

Factor VIII

Most common (85%) - Classic hemophilia

Factor IX

Christmas disease (15%)

X-linked

Recessive - males affected, females carriers

Memory Hook:ABX - A is VIII, B is IX, X-linked inheritance.

Mnemonic

Target Joints: KAE

Knee

Most common target joint

Ankle

Second most common

Elbow

Third most common

Memory Hook:KAE - Knee, Ankle, Elbow in order of frequency.

Mnemonic

Perioperative Protocol: CHIP

Coordinate haematology

Essential multidisciplinary planning

Hundred percent factor

Raise factor to 100% pre-op

Inhibitor check

Bethesda assay before surgery

Post-op maintain

50-80% factor level for 1-2 weeks

Memory Hook:CHIP away at perioperative planning.

Overview and Epidemiology

Hemophilia is an X-linked recessive bleeding disorder affecting males.

Types:

Hemophilia A: Factor VIII deficiency (85% of cases)
Hemophilia B: Factor IX deficiency (15%, "Christmas disease")

Incidence:

Hemophilia A: 1 in 5,000 male births
Hemophilia B: 1 in 30,000 male births

Inheritance:

X-linked recessive
Males affected (XY - single X chromosome)
Females are carriers (usually asymptomatic)
30% are new mutations (no family history)

Severity Classification:

Severe (under 1% factor activity): Spontaneous joint/muscle bleeds
Moderate (1-5%): Bleeding after minor trauma
Mild (5-40%): Bleeding after significant trauma/surgery

Pathophysiology

Coagulation Cascade:

Factor VIII (intrinsic pathway) accelerates Factor X activation
Factor IX activates Factor X (with Factor VIII as cofactor)
Deficiency leads to impaired thrombin generation and unstable clots

Hemophilic Arthropathy Development:

Hemarthrosis: Bleeding into joint space
Iron deposition: Hemoglobin breakdown releases iron (hemosiderin)
Synovitis: Iron-induced chronic synovial inflammation
Enzyme release: Synovial enzymes degrade cartilage
Cartilage destruction: Progressive chondrolysis
Secondary changes: Subchondral cysts, osteopenia, osteophytes
End-stage arthropathy: Joint destruction, contractures, disability

Target Joint Vulnerability:

Hinge joints (knee, ankle, elbow) more affected than ball-and-socket
Synovium is highly vascular - susceptible to bleeding
Repeated bleeds create vicious cycle: bleed to synovitis to more bleeds

Vicious Cycle: Hemarthrosis induces synovitis, which causes synovial proliferation and neovascularisation. The fragile new vessels bleed more easily, leading to recurrent hemarthroses and progressive joint destruction.

Imaging Findings in Hemophilic Arthropathy

Classification

Hemophilia Severity Classification

Classification based on factor activity level determines bleeding phenotype and treatment strategy.

Hemophilia Severity Classification

Severity	Factor Level	Bleeding Pattern
Under 1%	Spontaneous joint/muscle bleeds from infancy
1-5%	Bleeding after minor trauma, occasional spontaneous
5-40%	Bleeding after significant trauma or surgery

Most orthopaedic pathology occurs in severe hemophilia due to recurrent spontaneous hemarthroses.

Clinical Presentation

Acute Hemarthrosis

Presentation:

Acute onset joint pain (often atraumatic)
Warmth and swelling
Joint held in position of comfort (usually flexion)
Limited range of motion
May have prodromal tingling sensation ("aura")

History:

May recall minor trauma
May have been undertreated (missed prophylaxis)
Frequency of bleeds important for prognosis

Examination:

Tense effusion
Increased warmth
Tenderness on palpation
Guarding and muscle spasm
Check for other sites of bleeding

Acute hemarthrosis requires urgent factor replacement to arrest bleeding and minimise joint damage.

Investigations

Laboratory Investigations

Diagnostic:

Factor VIII assay: Reduced in Hemophilia A
Factor IX assay: Reduced in Hemophilia B
APTT: Prolonged (intrinsic pathway)
PT/INR: Normal (extrinsic pathway intact)
Bleeding time: Normal (platelet function intact)

Preoperative Workup:

Inhibitor screen (Bethesda assay): Critical - antibodies to factor
Factor level and recovery study
Blood group and crossmatch
Hepatitis B, C and HIV status (historical transfusion risk)
Full blood count
Liver function (may have hepatitis-related liver disease)

Monitoring:

Factor levels during treatment
Trough levels if on prophylaxis

Inhibitor development occurs in 25-30% of severe Hemophilia A patients and significantly complicates treatment.

Hemophilia A vs B:

Hemophilia A vs B

Feature	Hemophilia A	Hemophilia B
Factor VIII	Factor IX
85% of cases	15% of cases
Classic hemophilia	Christmas disease
Factor VIII concentrate	Factor IX concentrate
25-30% in severe	3-5% in severe

Management

Primary Prevention (Prophylaxis)

Standard of Care:

Regular factor replacement prevents hemarthroses
Start before or soon after first joint bleed
Aim: Maintain trough level above 1-5%

Prophylaxis Regimens:

Hemophilia A: Factor VIII 25-40 IU/kg every other day or 3x/week
Hemophilia B: Factor IX 25-40 IU/kg twice weekly

Evidence (Landmark JOG Study):

Manco-Johnson et al, NEJM 2007
Prophylaxis vs on-demand treatment
Prophylaxis group: 93% joint normal at 6 years
On-demand group: 55% joint normal
Prophylaxis is now standard of care

Extended Half-Life Products:

Reduce dosing frequency
Improved adherence
Better trough levels

Early prophylaxis prevents the development of hemophilic arthropathy.

Complications

Orthopaedic Complications:

Progressive joint destruction (arthropathy)
Fixed flexion contractures
Angular deformity (valgus/varus)
Muscle wasting and weakness
Limb length discrepancy
Pseudotumours (rare - encapsulated haematomas in soft tissue/bone)

Surgical Complications:

Intraoperative bleeding
Postoperative haematoma
Infection (higher rate than general population)
Wound healing problems
Stiffness (especially knee)
DVT/PE (paradoxical - still occurs)

Treatment Complications:

Inhibitor development: Antibodies to factor (25-30% Hemophilia A)
Transfusion-transmitted infections (historical - HCV, HIV)
Allergic reactions to factor concentrates
Central venous catheter complications (if port present)

Pseudotumour:

Rare but serious
Encapsulated haematoma in muscle or bone
Progressive enlargement if untreated
May erode bone
Treatment: Factor replacement, surgery if large

Outcomes

Prophylaxis Era Outcomes:

Joint disease markedly reduced
JOG study: 93% joints normal with prophylaxis at 6 years
Life expectancy approaching normal
Quality of life dramatically improved

Without Prophylaxis (Historical):

Severe arthropathy by adolescence
Wheelchair dependence common
Multiple joint replacements
Significant disability

Arthroplasty Outcomes:

Pain relief: 85-90% satisfied
Function improvement: Significant
Survivorship: 85-90% at 10 years
Complications higher than general population
Revision rate higher

Prognostic Factors:

Severity of hemophilia (severe worse)
Adherence to prophylaxis (critical)
Inhibitor status (inhibitors worsen prognosis)
Age at first bleed (earlier worse)
Number of target joints

Evidence Base

Level I - RCT

📚 Manco-Johnson MJ et al - JOG Study

Key Findings:

Prophylaxis vs on-demand treatment in severe Hemophilia A
Prophylaxis group: 93% joints normal at 6 years
On-demand group: 55% joints normal
Landmark study establishing prophylaxis as standard

Clinical Implication: Prophylaxis is standard of care for severe hemophilia - prevents arthropathy.

Source: N Engl J Med 2007

Review

📚 Rodriguez-Merchan EC

Key Findings:

Comprehensive orthopaedic management review
Synovectomy indications and techniques
Arthroplasty outcomes in hemophilia
Perioperative factor protocols

Clinical Implication: Comprehensive guide for orthopaedic management of hemophilia.

Source: Haemophilia 2012

Level IV

📚 Luck JV et al

Key Findings:

Radiosynovectomy with phosphorus-32
85% reduction in bleeding episodes
Safe and effective for chronic synovitis
Can repeat if needed

Clinical Implication: Radiosynoviorthesis effective for recurrent hemarthroses unresponsive to prophylaxis.

Source: J Am Acad Orthop Surg 2004

Level II

📚 Fischer K et al

Key Findings:

Early prophylaxis preserves joint health
Starting before age 3 prevents arthropathy
Cost-effective in long term
Reduces orthopaedic burden

Clinical Implication: Early prophylaxis (before age 3) is key to preventing hemophilic arthropathy.

Source: Blood 2002

Level IV

📚 Pasta G et al

Key Findings:

TKR in hemophilia - 20 year follow-up
Good pain relief and function
Higher revision rate than non-hemophiliacs
Acceptable long-term outcomes

Clinical Implication: TKR improves quality of life but expect higher complication rates than general population.

Source: Haemophilia 2008

Viva Scenarios

Practice these scenarios to excel in your viva examination

VIVA SCENARIOStandard

Acute Hemarthrosis

EXAMINER

"12-year-old boy with severe Hemophilia A presents with acute left knee swelling and pain after playing soccer. He is on regular prophylaxis but missed yesterday's dose."

EXCEPTIONAL ANSWER

This is an acute hemarthrosis in a known hemophiliac. The missed prophylaxis dose likely contributed to bleeding vulnerability.

Immediate management: Factor VIII replacement to raise level to 40-60%. Do not wait for investigations - treat first. Repeat doses may be needed (usually 1-3).

Supportive care (RICE): Rest (brief immobilisation), Ice, Compression, Elevation. Joint aspiration is controversial - consider only if very tense effusion with factor cover due to infection risk.

Early mobilisation: Once bleeding controlled, begin physiotherapy to maintain ROM. Prolonged immobilisation causes contractures.

Review prophylaxis: Discuss importance of adherence. Consider if regimen is adequate (may need dose adjustment).

KEY POINTS TO SCORE

Factor replacement first - do not delay

Raise factor to 40-60%

RICE for supportive care

Avoid prolonged immobilisation

Review prophylaxis compliance

COMMON TRAPS

✗Waiting for investigations before treating

✗Aspirating without factor cover

✗Prolonged immobilisation causing contracture

LIKELY FOLLOW-UPS

"What is the factor deficiency in Hemophilia A?"

"When would you aspirate a hemarthrosis?"

"What is the prophylaxis protocol for Hemophilia A?"

VIVA SCENARIOStandard

Severe Arthropathy - TKR Planning

EXAMINER

"35-year-old man with severe Hemophilia A, no inhibitors, presents with severe right knee arthropathy. Fixed 30-degree flexion contracture, valgus deformity, pain limiting mobility. Conservative management has failed."

EXCEPTIONAL ANSWER

This patient has end-stage hemophilic arthropathy of the knee and is a candidate for total knee replacement.

Preoperative workup (CHIP protocol):

Coordinate with haematology - essential, cannot proceed without them
Hundred percent factor VIII pre-operatively
Inhibitor screen (Bethesda assay) - critical, changes management entirely
Post-op plan: Maintain factor 50-80% for 10-14 days

Surgical considerations: May need constrained implant due to ligament laxity. Address fixed flexion contracture (posterior release). Expect higher blood loss and complication rate than standard TKR. Meticulous haemostasis intraoperatively.

Counselling: Higher complication rates (infection 5-10%, stiffness common), but good pain relief expected. Results improving with modern protocols.

KEY POINTS TO SCORE

Haematology coordination essential

CHIP protocol for perioperative planning

Check inhibitor status - changes management

Raise factor to 100% pre-op, maintain 50-80% post-op

Counsel about higher complication rates

COMMON TRAPS

✗Not checking inhibitor status

✗Not involving haematology

✗Underestimating complexity

✗Not counselling about complications

LIKELY FOLLOW-UPS

"What if the patient had inhibitors?"

"What factor levels do you maintain post-operatively?"

"What is the infection rate for TKR in hemophilia?"

VIVA SCENARIOStandard

Recurrent Hemarthroses Despite Prophylaxis

EXAMINER

"8-year-old boy with moderate Hemophilia A has recurrent right knee hemarthroses despite prophylaxis. X-ray shows early arthropathy with widened intercondylar notch. What do you recommend?"

EXCEPTIONAL ANSWER

This patient has a target joint with chronic synovitis leading to recurrent bleeds despite prophylaxis. The widened intercondylar notch is a classic radiographic sign of hemophilic knee arthropathy.

Assessment:

Confirm prophylaxis compliance and adequacy
Check trough factor levels - may need dose increase
MRI to assess synovitis severity
Consider inhibitor screen

Management options:

Optimise prophylaxis: Increase dose or frequency
Radiosynoviorthesis: Injection of radioactive isotope (P-32, Y-90). 85% reduction in bleeding episodes. Can repeat if needed. Low complication rate.
Arthroscopic synovectomy: If radiosynovectomy fails or unavailable

Radiosynoviorthesis is effective and minimally invasive - first-line after optimising prophylaxis.

KEY POINTS TO SCORE

Widened intercondylar notch is classic sign

Check prophylaxis compliance and levels

MRI to assess synovitis

Radiosynoviorthesis 85% effective

Consider arthroscopic synovectomy if radiosynovectomy fails

COMMON TRAPS

✗Not checking inhibitor status

✗Jumping to surgery without optimising prophylaxis

✗Missing inadequate trough levels

LIKELY FOLLOW-UPS

"What radioisotopes are used for radiosynovectomy?"

"What is the Arnold-Hilgartner classification?"

"When would you consider arthroscopic synovectomy?"

VIVA SCENARIOStandard

Inhibitor Patient

EXAMINER

"20-year-old with severe Hemophilia A needs elbow synovectomy for recurrent hemarthroses. Inhibitor screen shows Bethesda titre of 12 BU. How does this change your approach?"

EXCEPTIONAL ANSWER

This patient has a high-titre inhibitor (greater than 5 BU), which significantly complicates management. Standard Factor VIII replacement will be ineffective as antibodies neutralise the factor.

Management options:

Bypassing agents:
- FEIBA (Factor Eight Inhibitor Bypassing Activity) - activated prothrombin complex concentrate
- Recombinant Factor VIIa (rFVIIa, NovoSeven)
These bypass the need for Factor VIII in the coagulation cascade
Monitoring is more difficult (cannot use factor levels)

Considerations:

Higher bleeding risk than non-inhibitor patients
More challenging perioperative management
Expert haematology input essential
May need to consider immune tolerance induction for long-term

High-titre inhibitor patients should be managed in specialist centres with haemophilia expertise.

KEY POINTS TO SCORE

High-titre inhibitor (greater than 5 BU) - standard factor ineffective

Use bypassing agents: FEIBA or rFVIIa

Cannot monitor with factor levels

Higher bleeding risk

Specialist centre management

COMMON TRAPS

✗Using standard factor replacement

✗Not recognising high-titre vs low-titre difference

✗Proceeding without specialist input

LIKELY FOLLOW-UPS

"What is immune tolerance induction?"

"How do you differentiate high-titre from low-titre inhibitors?"

"What are the mechanisms of bypassing agents?"

Australian Context

Epidemiology:

Approximately 2,800 Australians with hemophilia
80% Hemophilia A, 20% Hemophilia B
Managed through Australian Hemophilia Centre Directors' Organisation (AHCDO)

Treatment Access:

Factor concentrates available through National Blood Authority
Covered by government (Lifeblood/National Blood Arrangements)
Extended half-life products increasingly available

Specialist Centres:

Haemophilia Treatment Centres in each state
Multidisciplinary care model
Comprehensive care including orthopaedics, physiotherapy, social work

PBS Considerations:

Factor concentrates listed on National Product List
Extended half-life products available
Emicizumab (non-factor therapy) available for inhibitor patients

Referral Pathways:

All hemophilia patients should be registered with a Haemophilia Treatment Centre
Orthopaedic procedures require coordination with HTC
National guidelines through AHCDO