Haemophilic Arthropathy

Haemophilic arthropathy is the progressive joint destruction that results from recurrent intra-articular haemorrhage (haemarthrosis) in patients with haemophilia A (factor VIII deficiency) or haemophilia B (factor IX deficiency). It is the most debilitating musculoskeletal complication of haemophilia and a major determinant of quality of life. Understanding the pathophysiology of synovial iron deposition, cartilage degradation, and the principles of both preventative and reconstructive management is essential for the orthopaedic surgeon caring for haemophilia patients.

• Haemophilia A: deficiency of factor VIII; X-linked recessive; incidence approximately 1 in 5,000 male births
• Haemophilia B: deficiency of factor IX; X-linked recessive; incidence approximately 1 in 30,000 male births
• Severity classification: severe <1% factor activity; moderate 1–5%; mild 5–40% — severe haemophilia is responsible for the vast majority of haemarthroses and arthropathy
• Most commonly affected joints: knee (45%), elbow (30%), ankle (15%) — these are called the "target joints"; hip, shoulder, and wrist less commonly affected
• Pathophysiology of arthropathy: acute haemarthrosis → iron deposition in synovium (haemosiderin) → chronic synovitis → proliferative synovial pannus → cartilage degradation by metalloproteinases, iron-induced free radical damage, and direct chondrocyte toxicity → subchondral bone erosion → arthropathy
• A single acute haemarthrosis triggers synovial iron deposition and initiates the inflammatory cascade — even one missed or inadequately treated haemarthrosis can accelerate joint deterioration; this is the rationale for aggressive prophylactic factor replacement

The Arnold-Hilgartner classification grades haemophilic arthropathy of the knee based on radiographic findings.

• Primary prophylaxis: regular factor VIII or IX infusions from early childhood (before first joint bleed or from age 1–2 years) — proven to prevent arthropathy; standard of care in developed nations; target trough factor level >1–3%; three times weekly for FVIII, twice weekly for FIX
• On-demand (episodic) treatment: factor replacement given only at time of bleed — associated with significantly higher rates of arthropathy compared to prophylaxis; still used in resource-limited settings
• Inhibitors: approximately 25–30% of severe haemophilia A patients develop factor VIII inhibitors (neutralising antibodies); render standard factor replacement ineffective; manage with bypassing agents — recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrate (aPCC, FEIBA); emicizumab (monoclonal antibody) is now used for inhibitor patients — does not require frequent infusions; given subcutaneously weekly/monthly
• Emicizumab (Hemlibra): bispecific antibody mimicking FVIII function — bridges FIXa and FX; approved for haemophilia A with and without inhibitors; subcutaneous injection weekly/fortnightly/monthly; dramatically reduces bleed rate; does not replace FVIII and does not correct laboratory APTT — important for surgical planning (use FVIII level not APTT for monitoring during surgery in these patients)
• DDAVP (desmopressin): stimulates endogenous FVIII release; useful in mild haemophilia A for minor procedures; no effect in severe haemophilia A or any haemophilia B

• RICE protocol: rest, ice, compression, elevation — adjuncts to factor replacement
• Factor replacement: first-line treatment — raise FVIII/FIX level to 50% (moderate bleed) or 80–100% (severe/large joint bleed); administer within 2 hours of symptom onset for best outcomes
• Aspiration of tense haemarthrosis: under factor cover; reduces pain, synovial iron load, and prevents cartilage damage; performed when joint is tense and painful despite factor replacement — must be performed with adequate factor cover (aim for >50% factor level) to prevent continued bleeding
• NSAIDs: COX-2 inhibitors only — traditional NSAIDs impair platelet function and increase bleeding risk; celecoxib acceptable adjunct for pain
• Tranexamic acid: antifibrinolytic; useful adjunct for mucosal bleeds and some joint bleeds; reduces clot lysis

All surgery in haemophilia must be planned in close collaboration with the haematology team. Factor levels must be optimised preoperatively and maintained throughout the perioperative period. Surgery in patients with inhibitors requires specialist haemophilia centre input.

• TKA in haemophilic arthropathy: produces excellent pain relief and functional improvement; technically demanding due to stiff, distorted joint, poor bone quality, and periarticular fibrosis; higher complication rate than primary OA TKA including infection (3–5%), stiffness, and wound healing problems; constrained implants often needed
• Tourniquets: can be used to reduce blood loss intraoperatively but require haematology guidance; inflate only after factor infusion and exsanguination; deflate and achieve haemostasis before wound closure
• Cell salvage and tranexamic acid: adjuncts to reduce blood loss; cell salvage acceptable in haemophilia surgery as autologous blood

• Haemophilia + HIV/HCV: many older haemophilia patients (treated before 1985) received contaminated blood products — significant proportion carry HIV and/or hepatitis C; HIV increases arthropathy severity and operative infection risk; HCV causes liver disease affecting coagulation factor production; co-management with infectious disease and hepatology essential before any major surgery
• Pseudo-tumour of haemophilia: expanding haematoma enclosed by a fibrous capsule — can erode adjacent bone, cause pathological fracture, and compress neurovascular structures; appears as a lytic bone lesion on imaging; management by aspiration and factor cover for small lesions; surgical excision for large or enlarging pseudotumours; embolisation for vascular supply; high-risk surgery requiring specialist centre
• Gene therapy for haemophilia: several products now licensed (valoctocogene roxaparvovec for HA, etranacogene dezaparvovec for HB); single IV infusion of adeno-associated virus (AAV) vector; provides sustained FVIII or FIX production from transduced hepatocytes; significant reduction in bleed rate; not a permanent cure — expression declines over years; long-term orthopaedic implications evolving
• Emicizumab and surgery: emicizumab does not restore normal haemostasis — major surgery requires additional factor replacement over emicizumab base; cannot use aPCC with emicizumab (risk of thrombotic microangiopathy); use recombinant FVIIa as bypassing agent if needed; always involve haematology centre
• Flexion contracture in haemophilic knee: common long-term sequela; serial casting, physiotherapy, and dynamic splinting for mild contractures; surgical capsular release ± osteotomy for severe fixed contracture; TKA corrects deformity in end-stage arthropathy but constrained implants often needed

• Haemophilia A: FVIII deficiency; Haemophilia B: FIX deficiency; both X-linked recessive; severe = <1% factor activity
• Target joints: knee (45%), elbow (30%), ankle (15%) — sites of most frequent haemarthrosis and worst arthropathy
• Pathophysiology: haemarthrosis → haemosiderin in synovium → chronic synovitis → pannus → cartilage destruction → arthropathy
• Arnold-Hilgartner Grade V = complete joint destruction = end-stage = TKA or arthrodesis
• Primary prophylaxis: standard of care; prevents arthropathy; start in early childhood before first joint bleed; trough level target >1–3%
• Inhibitors: 25–30% of severe HA; neutralise FVIII; manage with rFVIIa or aPCC (bypassing agents); emicizumab for long-term prophylaxis
• TKA in haemophilia: factor level >100% perioperatively; maintain >50–80% for 14 days post-op; haematology team essential
• Pseudo-tumour: expanding haematoma eroding bone; aggressive management — aspiration, factor cover, surgery or embolisation for large lesions
• Do NOT use standard NSAIDs (impair platelets) — COX-2 inhibitors (celecoxib) acceptable
• Emicizumab: bispecific antibody; mimics FVIII; subcutaneous; does not normalise APTT — monitor factor level not APTT during surgery