Haemophilic Joint (Haemophilic Arthropathy)

Background and Pathophysiology

• Tissue factor expression is relatively low in synovium, making thrombin generation dependent on the intrinsic tenase complex (factors VIII and IX)
• Tissue factor pathway inhibitor is relatively high in the joint
• Inadequate thrombin-activatable fibrinolysis inhibitor (TAFI) activation means local fibrinolysis is increased
• Neovascularization triggered after a first bleed creates fragile new vessels prone to repeated injury

Joints Affected

• Knees, ankles, elbows (most common - large synovial joints)
• Hips, shoulders (less common)
• Small joints of hands and feet (rare)

Clinical Stages

1. Acute Hemarthrosis

• The first joint bleed typically occurs at ~1.8 years of age (when the child starts walking)
• Prodrome: tingling sensation and tightness within the joint
• Followed by: rapid swelling, loss of range of motion (ROM), pain, warmth
• Flexion is the most comfortable position; disuse causes secondary muscle spasm
• Blood stays liquid in the joint due to absence of intrinsic clotting factors and tissue thromboplastin in synovium
• Blood is resorbed over ≥1 week; full recovery within ~2 weeks with factor replacement
• Fever >38.3°C warrants concern for septic arthritis (rare but serious)

2. Synovitis (Chronic)

• Synovium cannot fully remove blood remnants
• Iron accumulates as hemosiderin deposits in synovium and cartilage
• Iron triggers inflammatory response, stimulating synoviocyte proliferation
• Pro-inflammatory cytokines (including IL-1, TNF, VEGF) released
• New fragile blood vessels form (neovascularization) - predisposing to further bleeds

3. Established Haemophilic Arthropathy

Progressive synovial fibrosis paradoxically reduces hemarthrosis frequency in end-stage disease.

Associated Musculoskeletal Complications

• Common sites: iliopsoas and flexor compartment of forearm
• Iliopsoas bleed: pain in lower abdomen/groin/lower back, pain on hip extension but not rotation (distinguishes from hemarthrosis)
• Risk of compartment syndrome - a life-threatening emergency
• Hip flexion contracture from iliopsoas involvement; femoral neuropathy from nerve compression

• Form when periosteum or bone is involved
• In children: distal to elbows/knees, from direct trauma, often responsive to conservative treatment
• In adults: femur and pelvis, usually refractory to treatment
• Appear as expanding, painful bony swellings

Radiographic changes of haemophilic arthropathy: (A) Left elbow, (B) Right knee, (C) Right ankle - showing joint space narrowing and subchondral cysts. (Firestein & Kelley's Textbook of Rheumatology)

Radiographic Findings (Progression)

Diagnosis

Treatment

Acute Hemarthrosis

• Immediate factor VIII or IX infusion at first sign of bleeding
• Splint in gentle forced extension to prevent contracture
• Analgesia: avoid non-selective NSAIDs (inhibit platelets); COX-2 inhibitors are safer
• In patients with inhibitors (anti-factor antibodies): recombinant activated factor VIIa or activated prothrombin complex concentrate

Chronic Synovitis

• Clotting factor replacement (long-term) to break the hemarthrosis-synovitis cycle
• Radiosynovectomy with yttrium-90 silicate or phosphorus-32 colloid: effective, preferred when surgery is not advised
• Synovectomy (arthroscopic preferred over open): limits future bleeding and fibrosis; open procedure risks decreased ROM

Established Arthropathy - Conservative

• Analgesics, physiotherapy (muscle strengthening, stretching, joint stability)
• Manual traction, TENS
• Hydrotherapy (functional training with minimal weight-bearing)
• Orthotics/shoe adaptations, casting

Established Arthropathy - Surgical

Prevention

• Firestein & Kelley's Textbook of Rheumatology, Chapter 124 (Haemophilic Arthropathy)
• Harrison's Principles of Internal Medicine 22E (2025), Chapter 386 (Haemophilic Arthropathy)

Postoperative Pain Management in Orthopaedics

Why Pain Management Matters in Orthopaedics

• Sympathetic activation - hypertension, tachycardia, dysrhythmias
• Impaired early mobilisation and rehabilitation
• Risk of chronic pain, central sensitization, and complex regional pain syndrome (CRPS)
• Poor patient satisfaction (patient perception of pain control affects satisfaction more than the quantity of opioid prescribed)

Assessment of Pain

• Characteristics: onset, duration, location, quality, intensity
• Past and current management strategies
• Impact on daily activities and patient goals

• Numeric Rating Scale (NRS): 0-10 (most widely used)
• Visual Analog Scale (VAS): 10-cm horizontal scale
• Verbal/visual descriptors for non-communicating patients (grimacing, restlessness, vocalisation, vital signs)

• Within 30 minutes after parenteral drug administration
• Within 1 hour after oral drug administration
• With any new or changed pain

Respiratory depression in opioid users can be as high as 48%; sedation precedes respiratory depression and is the more reliable early warning sign.

Preoperative Considerations

• Screen all patients for opioid risk (abuse, misuse, diversion potential) before prescribing
• Patients on chronic NSAIDs (RA/OA): note risks of GI bleeding, renal toxicity, platelet dysfunction
• Preoperative regional anaesthesia ("block room") can be performed in a preoperative holding area to avoid OR delays
• Patients with prior opioid use or chronic pain have altered central pain processing and require tailored regimens
• The psychological state of the patient (catastrophizing) affects pain perception and outcomes; identify and address preoperatively

The Multimodal Analgesia Principle

• Reduces total opioid consumption (opioid-sparing)
• Minimises opioid side effects (nausea, sedation, respiratory depression, addiction risk)
• Improves functional recovery and facilitates physiotherapy
• Reduces length of hospital stay

1. Pharmacological Agents

A. Paracetamol (Acetaminophen)

• First-line non-opioid analgesic; also antipyretic
• IV form allows administration in perioperative NPO period
• Safe in most adults and children; use with caution in hepatic disease
• Core component of all multimodal regimens

B. NSAIDs

• Act by inhibiting cyclooxygenase (COX) → reduced prostaglandin synthesis → analgesia + anti-inflammatory
• Examples: ibuprofen, naproxen, meloxicam, ketorolac
• Ketorolac (IV/IM): highly effective for musculoskeletal and post-fracture pain; recent evidence supports use even after fracture surgery without significantly increased nonunion risk when used short-term
• COX-2 inhibitors (celecoxib): equivalent analgesia, do not impair platelet function (safer perioperatively), but carry cardiovascular, renal, and GI concerns
• Historic concern about NSAIDs impairing bone healing is now considered of less significance for short-term use
• Non-selective NSAIDs should be avoided if possible in patients with bleeding risk (platelet dysfunction)

C. Opioids

• Act on mu, delta, kappa receptors in brain, spinal cord, and peripheral nociceptors
• Also stimulate mesolimbic dopamine system (addiction potential)
• Remain essential for moderate-to-severe acute pain
• Risks: respiratory depression, sedation, constipation, nausea, addiction, possible delayed bone healing (animal data, not robustly shown in humans)
• Tramadol: weak opioid agonist + serotonin/noradrenaline reuptake inhibitor; useful for moderate pain (step-down from stronger opioids)
• Key principle: use at the lowest effective dose for the shortest duration, with a clear prescription limit (e.g. no refills, maximum 2 prescriptions)

D. Gabapentinoids (Gabapentin / Pregabalin)

• Block voltage-gated calcium channels → reduce neurotransmitter release
• Useful as adjuncts for neuropathic pain components
• Opioid-sparing effect: a 2025 systematic review (PMID 41239206) confirms effectiveness in orthopedic surgeries for postoperative pain and opioid-sparing
• Short-term use post-discharge (e.g. gabapentin 100 mg TID × 5 days) is favoured
• Side effects: sedation, dizziness - exercise caution especially in elderly

E. Muscle Relaxants

• Cyclobenzaprine, metaxalone, methocarbamol
• Central action to reduce muscle spasm
• Useful where muscle spasm contributes significantly to pain (e.g. spinal surgery, pelvic injuries)

F. Corticosteroids (Dexamethasone)

• Perioperative single dose reduces postoperative pain and nausea
• Used in selected cases

2. Regional / Neuraxial Techniques

Neuraxial (Spinal / Epidural) Anaesthesia

• Spinal (intrathecal) opioids (morphine, hydromorphone): provide extended postoperative analgesia; widely used with enhanced recovery protocols
• Epidural analgesia: useful after bilateral TKA; provides excellent pain control but more side effects (pruritus, nausea/vomiting, urinary retention, orthostatic hypotension) than peripheral nerve blocks
• Neuraxial techniques are associated with lower rates of all-cause infections, AKI, pulmonary/thromboembolic complications, and falls compared with general anaesthesia alone in hip/knee arthroplasty

Peripheral Nerve Blocks (PNBs)

• Single-shot provides satisfactory analgesia for several hours
• Continuous perineural catheters (with local anaesthetic infusion) decrease time to discharge criteria for TKA and are preferred for major procedures
• For unilateral TKA: perineural catheters provide equivalent analgesia to epidural catheters with fewer side effects and earlier ambulation
• Requires 24/7 team coverage; fall prevention programs are essential

Intra-articular (Local Infiltration Analgesia - LIA)

• Surgeon-administered injection of local anaesthetic (bupivacaine/ropivacaine) ± adjuvants into the joint space
• Adjuvants: opioids, clonidine, ketorolac, epinephrine, neostigmine - extend duration
• Particularly used in arthroscopic procedures and arthroplasty
• Periarticular infiltration by surgeon during TKA is widely practised with good evidence

Ultrasound Guidance

• Has greatly improved accuracy and safety of nerve blocks
• Reduces risk of intravascular injection and neurological complications

3. Procedure-Specific Highlights

Total Hip Arthroplasty (THA)

• Neuraxial anaesthesia preferred (reduces mortality/morbidity)
• Intrathecal opioids for extended analgesia
• Lumbar plexus / fascia iliaca / PENG blocks effective
• Multimodal: paracetamol + NSAID/COX-2 + regional ± opioid PRN

Total Knee Arthroplasty (TKA)

• Pain is more severe and longer-lasting than after THA
• Effective multimodal analgesia is essential for early ROM and preventing joint adhesions
• Balance between pain control and alertness during physiotherapy
• Adductor canal block preserves motor function (preferred over femoral nerve block for mobilisation)
• Perineural catheters preferred over epidural for unilateral TKA
• Periarticular infiltration by surgeon is standard practice

Shoulder Surgery

• Interscalene block provides excellent analgesia
• Continuous interscalene catheter for major open procedures
• Position-related hypotension (beach chair position) must be monitored separately

Fracture Surgery / Trauma

• Peripheral nerve blocks at time of presentation reduce pre-operative and perioperative pain
• Brachial plexus block for upper limb fractures
• Popliteal block for ankle fractures
• Fascia iliaca / PENG for hip fractures (reduces opioid requirement acutely)
• Short-term NSAIDs now acceptable even in fracture patients
• Opioids: prescribe with specific limits; avoid chronic prescribing

Spine Surgery

• Combination of wound infiltration, epidural analgesia, and systemic multimodal agents
• NSAIDs used with caution (theoretical concern for spinal fusion, though evidence mixed)

4. Authors' Preferred Regimen (Rockwood & Green's Orthopaedics)

• Minor injury: Tramadol 50 mg q6h PRN (#20 → #10) + NSAID + paracetamol
• Major injury: Hydrocodone/paracetamol (#20 → #10) + NSAID + paracetamol

5. Non-Pharmacological Strategies

6. Enhanced Recovery After Surgery (ERAS) in Orthopaedics

• Preoperative: education, optimisation, preemptive analgesia (gabapentinoids, celecoxib)
• Intraoperative: neuraxial anaesthesia, tranexamic acid, LIA
• Postoperative: early mobilisation, scheduled multimodal non-opioid analgesia, VTE prophylaxis, physiotherapy

7. Special Considerations

• Require higher baseline opioid doses; liaise with pain specialists
• Target concurrent non-opioid and regional strategies aggressively

• Increased sensitivity to opioids (sedation, falls, delirium)
• Start low with opioids; prefer non-opioid multimodal approaches
• Screen for renal function before NSAIDs

• Screen all patients with validated risk tools before opioid prescription
• Use prescription drug monitoring programs (PDMPs)
• Prescribe the minimum necessary; avoid refills where possible
• The patient's perception that pain is being managed matters more than total opioid quantity prescribed

• Ensure adequate early postoperative analgesia
• Early mobilisation and physiotherapy
• Vitamin C supplementation has been proposed for fracture patients (particularly distal radius) to reduce CRPS risk

• Rockwood and Green's Fractures in Adults, 10th ed. (2025), Chapters 28-29
• Morgan and Mikhail's Clinical Anesthesiology, 7e, Chapters 38, 6C
• Barash, Cullen & Stoelting's Clinical Anesthesia, 9e, Chapters 15, 19
• Schwartz's Principles of Surgery, 11th ed., Chapter on Postoperative Pain

• Gabapentinoids in orthopaedic surgery - effective for pain and opioid-sparing (PMID 41239206, BMC Anesthesiology 2025)
• Peripheral nerve blocks for THA - network meta-analysis supporting their efficacy and safety (PMID 41136958, BMC Anesthesiology 2025)
• Non-opioid protocols for TKA/THA - updated meta-analysis confirming non-opioid multimodal regimens are effective (PMID 39551408, Journal of Arthroplasty 2025)