Sickle Cell Disease: Orthopaedic
Vaso-occlusion and Bone Complications
Orthopaedic Complications
Critical Must-Knows
- HbS: Glutamate to valine substitution at position 6 of beta-globin chain
- Vaso-occlusion: Sickling under hypoxia/acidosis causes bone infarcts, AVN, painful crises
- AVN: Femoral head (10-30%), humeral head - often bilateral
- Osteomyelitis: SALMONELLA is most common organism (unique to SCD, unlike general population)
- Perioperative: Avoid hypothermia, hypoxia, dehydration, acidosis - transfuse HbS to less than 30%
Examiner's Pearls
- "Salmonella osteomyelitis
- "H-shaped vertebrae
- "Bilateral AVN common
- "Hydration critical perioperatively
Critical Exam Point: Osteomyelitis Organism
In Sickle Cell Disease, the most common osteomyelitis organism is SALMONELLA.
- This is UNIQUE to SCD - viva examiners will test this
- Staph aureus is still common but Salmonella is MORE common
- Empiric antibiotics MUST cover BOTH organisms
- Autosplenectomy increases infection susceptibility
Mnemonics for Exam Recall
At a Glance
Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy caused by the HbS mutation (glutamate to valine at position 6). Sickling of red cells under hypoxia causes vaso-occlusion leading to bone infarcts, painful crises, and avascular necrosis (10-50% prevalence, commonly bilateral femoral head). The critical exam point is that Salmonella is the most common osteomyelitis organism in SCD (unique to this condition), requiring dual antibiotic coverage. Perioperative management must avoid the "5 Hs" that trigger sickling: Hypoxia, Hypothermia, Hypovolemia (dehydration), Hydrogen ions (acidosis), and Hypotension. Preoperative exchange transfusion targets HbS under 30%.
SCD Orthopaedic Complications
Memory Hook:SICKLE - the shape that causes the disease reminds you of all complications.
Perioperative Protocol: CHANT
Memory Hook:CHANT the mantra to avoid sickling crisis.
Radiographic Signs
Memory Hook:HAIR on end skull appearance from marrow expansion.
Overview and Epidemiology
Sickle Cell Disease (SCD) is a hereditary hemoglobinopathy with significant orthopaedic manifestations.
Genetics:
- Inheritance: Autosomal recessive
- Mutation: HBB gene - Glutamate to Valine substitution at position 6 (Glu6Val)
- Genotypes: HbSS (most severe), HbSC (milder), HbS-beta thalassemia
Epidemiology:
- Prevalence: Common in populations from malaria-endemic regions
- African descent: 1 in 500 African Americans affected
- Australia: Increasing prevalence with migration patterns
- Life expectancy: Improved to 40-60 years with modern care
Pathophysiology and Mechanisms
Molecular Basis:
- HbS Formation: Single nucleotide mutation in beta-globin gene (Glu6Val)
- Deoxygenation triggers polymerization: HbS molecules aggregate when deoxygenated
- Polymer formation: Long polymer fibres distort red cell membrane into sickle shape
- Membrane damage: Repeated sickling causes irreversible membrane damage
Vaso-occlusive Mechanism:
- Sickled cells are rigid and adhere to endothelium
- Obstruction of microvasculature (capillaries, sinusoids)
- Ischemia of downstream tissues
- Reperfusion injury with inflammatory response
Bone-Specific Pathophysiology:
- Marrow infarction: Leads to painful crises and bone necrosis
- End-artery occlusion: Particularly affects epiphyses (AVN) and endplates (H-vertebrae)
- Marrow hyperplasia: Compensatory expansion to combat chronic haemolysis
- Cortical thinning: Secondary to marrow expansion
- Increased infection risk: Functional asplenia + micro-infarcts create nidus
Precipitating Factors (CHAID):
- Cold exposure
- Hypoxia
- Acidosis
- Infection
- Dehydration
Radiographic Features
Clinical Presentation
Painful Vaso-occlusive Crisis
Presentation:
- Severe bone pain - often diaphyseal
- Dactylitis (hand-foot syndrome) in children less than 3 years
- Long bone pain in older children and adults
- No fever or mild low-grade temperature
Triggers:
- Dehydration
- Infection
- Cold exposure
- High altitude/hypoxia
- Physical exertion
Clinical Features:
- Swelling and tenderness over affected bones
- No fluctuance or abscess
- Often multiple sites
- Duration typically 4-7 days
Vaso-occlusive crisis is the most common acute complication requiring hospitalisation.
Investigations
Laboratory Investigations
Haematology:
- Full blood count: Chronic anaemia (Hb 6-9 g/dL typical)
- Reticulocyte count: Elevated (chronic haemolysis)
- Blood film: Sickled cells, Howell-Jolly bodies (asplenia)
- Haemoglobin electrophoresis: Confirms HbSS, HbSC, or HbS-thal
Infection Workup:
- Blood cultures (if febrile)
- CRP, ESR: Elevated in infection
- Procalcitonin: May help differentiate crisis from infection
- WCC: Very elevated suggests infection vs mild elevation in crisis
Preoperative:
- Group and hold/crossmatch
- Coagulation studies
- Renal function (may have sickle nephropathy)
- Liver function (iron overload from transfusions)
HbS percentage is critical for surgical planning - target less than 30%.
Differentiating Crisis vs Osteomyelitis:
Vaso-occlusive Crisis vs Osteomyelitis
| Feature | Vaso-occlusive Crisis | Osteomyelitis |
|---|---|---|
| Acute (hours) | Subacute (days to weeks) | |
| Low-grade or absent | High-grade (38.5C or higher) | |
| Normal or mildly elevated | Significantly elevated | |
| Mildly elevated (under 100) | Markedly elevated (over 100) | |
| Often multifocal | Usually single focus | |
| Marrow oedema only | Periosteal reaction, soft tissue changes, abscess | |
| 4-7 days typical | Weeks if untreated | |
| Good improvement | Minimal improvement |
Management
Vaso-occlusive Crisis Management
Acute Management:
- Hydration: IV fluids at 1.5x maintenance
- Analgesia: Often requires opioids (morphine PCA)
- Oxygen: If SpO2 less than 95%
- Warmth: Maintain normothermia
- Transfusion: Simple transfusion if severe
Supportive Care:
- Rest
- NSAIDs (caution with renal function)
- Antiemetics if needed
- Monitor for complications
Escalation Criteria:
- Acute chest syndrome (fever, respiratory symptoms, new infiltrate)
- Severe anaemia (Hb less than 5 g/dL)
- Stroke symptoms
- Priapism lasting more than 4 hours
Most crises resolve within 4-7 days with supportive care.
Complications
Orthopaedic Complications:
- Avascular necrosis: 10-50% develop AVN of femoral head, humeral head
- Pathological fractures: Weakened bone prone to fracture
- Chronic osteomyelitis: Recurrent or incompletely treated infections
- Growth disturbance: Limb length discrepancy, angular deformity
- Joint contractures: From repeated crises and immobilisation
Surgical Complications:
- Infection: 10-15% (vs 1-2% general population)
- Sickling crisis: Perioperative trigger by hypoxia/hypothermia
- Acute chest syndrome: Postoperative complication, potentially life-threatening
- Wound healing: Delayed healing common
- Implant failure: Earlier loosening and revision
Systemic Complications:
- Acute chest syndrome: Most common cause of death in SCD
- Stroke: Occurs in 10% of children with SCD
- Renal failure: Sickle nephropathy
- Pulmonary hypertension: From chronic haemolysis
- Iron overload: From chronic transfusions
Outcomes
AVN Surgery Outcomes:
- THA survivorship: 80-90% at 10 years (lower than general population)
- Infection rate: 10-15%
- Dislocation rate: Increased
- Revision rate: Higher due to loosening and infection
Prognostic Factors:
- HbSS genotype: Worse prognosis than HbSC
- Frequent crises: Associated with more complications
- Age: Earlier AVN associated with worse long-term outcomes
- Transfusion burden: Iron overload complications
Life Expectancy:
- Modern care: Median survival 40-60 years
- Hydroxyurea: Reduces crisis frequency, improves survival
- Stem cell transplant: Potentially curative in selected patients
Comparison: SCD vs General Population Arthroplasty:
THA Outcomes: SCD vs General Population
| Outcome | SCD | General Population |
|---|---|---|
| 80-90% | 95-98% | |
| 10-15% | 1-2% | |
| Increased | 1-3% | |
| Earlier failure | 1-2% at 10 years | |
| Higher | Standard |
Evidence Base
- Long-term outcomes of THA in SCD patients
- 10-year survivorship 80-90%
- Higher infection and revision rates
- Cementless fixation showed good results
- Osteomyelitis in sickle cell disease review
- Salmonella most common organism (50-70%)
- Multifocal disease in 25%
- Empiric coverage of both Salmonella and Staph essential
- AVN prevalence 10-50% in SCD (increases with age)
- More common in HbSS than HbSC genotype
- Bilateral involvement in 50%
- Alpha-thalassemia trait may be protective
- Simple vs aggressive transfusion protocols compared
- Simple transfusion (target Hb 10 g/dL) as effective
- Aggressive transfusion (target HbS less than 30%) had more complications
- Simple protocol now standard for minor/moderate surgery
- Evidence-based guidelines for SCD management
- Hydroxyurea recommended for frequent crises
- Chronic transfusion for stroke prevention
- Multidisciplinary care improves outcomes
Viva Scenarios
Practice these scenarios to excel in your viva examination
Osteomyelitis in SCD Child
"10-year-old with known sickle cell disease (HbSS) presents with fever 39C, right tibial pain and swelling for 1 week. Mum says it's different from his usual pain crises."
This presentation is concerning for osteomyelitis rather than vaso-occlusive crisis. Key differentiating features: prolonged duration (1 week), high fever (39C), localised single site, and mother's observation that it differs from usual crises.
Key point for examiners: In SCD, the most common osteomyelitis organism is SALMONELLA, not Staph aureus as in the general population. This is unique to SCD due to functional asplenia and GI translocation.
Investigations: Blood cultures, FBC (WCC elevated), CRP (markedly elevated in infection), MRI (gold standard - will show periosteal reaction, soft tissue changes, potentially abscess in osteomyelitis).
Treatment: Empiric IV antibiotics covering BOTH Salmonella AND Staph aureus - e.g., 3rd generation cephalosporin (ceftriaxone) plus flucloxacillin. Duration 4-6 weeks IV. Surgical debridement if abscess present or no response to antibiotics.
Perioperative Management for THA
"Same patient now 30 years old requires total hip arthroplasty for Ficat Stage IV AVN of right hip. How do you prepare him for surgery?"
Preoperative management is critical to avoid perioperative sickling crisis.
Haematology consultation: Essential for transfusion planning. Check haemoglobin electrophoresis for HbS percentage.
Transfusion protocol: Simple transfusion to achieve Hb approximately 10 g/dL is standard for most procedures. For major surgery like THA, may consider exchange transfusion to reduce HbS to less than 30%. The NHLBI Preoperative Transfusion Study (Vichinsky, NEJM 1995) showed simple transfusion is as effective as aggressive exchange for moderate-risk procedures.
Intraoperative (CHANT mnemonic): Cold avoidance (forced air warming, warm fluids), Hydration (liberal IV fluids), Acidosis prevention, Normal oxygenation (maintain SpO2 greater than 95%), Tourniquet use controversial.
Postoperative: ICU/HDU monitoring, continue hydration and oxygen, incentive spirometry (prevent acute chest syndrome), early mobilisation, VTE prophylaxis.
Counsel patient: Higher complication rates - infection 10-15%, dislocation increased, earlier loosening compared to general population.
AVN in Young SCD Patient
"22-year-old woman with HbSS sickle cell disease presents with 3-month history of bilateral hip pain and limp. X-rays show early sclerosis of both femoral heads without collapse."
This is bilateral AVN of the femoral heads, which is common in SCD (50% of AVN cases are bilateral). The presentation of bilateral hip pain and early radiographic changes (Ficat Stage II - sclerosis without collapse) is typical.
Further investigation: MRI both hips to accurately stage disease and assess extent of femoral head involvement. MRI may detect earlier disease than X-ray and helps prognosticate.
Management approach:
- Activity modification: Protected weight-bearing, avoid high-impact activities
- Core decompression: May be considered for pre-collapse disease to delay progression. Success rates lower in SCD than idiopathic AVN.
- Monitoring: Serial imaging to assess for progression
- Joint preservation: Goal is to delay arthroplasty given young age and known higher complication rates
If progression to collapse occurs, THA will eventually be required but should be delayed as long as possible given poor survivorship.
H-Shaped Vertebrae Finding
"You are shown a lateral spine X-ray of a 15-year-old with sickle cell disease showing characteristic central endplate depression of multiple vertebral bodies. Describe the findings and explain the pathophysiology."
The image shows H-shaped vertebrae (also called Lincoln log sign), which is pathognomonic for sickle cell disease.
Radiographic description: Central depression of the superior and inferior vertebral endplates creating an H or Lincoln log appearance on lateral view. Multiple vertebral levels are affected.
Pathophysiology: The central portion of the vertebral endplate receives its blood supply from end-arteries that are vulnerable to vaso-occlusion. Sickling episodes cause repeated microinfarcts of the central endplate zone. The peripheral endplate is relatively spared due to collateral blood supply from the annulus fibrosus vessels. Over time, repeated infarcts cause growth arrest centrally while peripheral growth continues, resulting in the characteristic stepped appearance.
Clinical significance: H-shaped vertebrae rarely require specific treatment and are usually an incidental finding. They represent cumulative bone damage from vaso-occlusive episodes. Associated findings may include fish-mouth or codfish vertebrae (biconcave deformity) and bone-in-bone appearance.
Australian Context
Epidemiology in Australia:
- Increasing prevalence with migration from Africa, Middle East
- Estimated 1,000-2,000 Australians affected
- Major centres in Sydney, Melbourne with SCD expertise
PBS Considerations:
- Hydroxyurea: PBS listed for SCD
- Iron chelation therapy if transfusion-dependent
Referral Pathways:
- Specialist haematology centres for comprehensive care
- Paediatric haematology for children
- Multidisciplinary approach essential
MCQ Practice Points
Exam Pearl
Q: What is the most common cause of osteomyelitis in patients with sickle cell disease?
A: Salmonella species is the most common organism causing osteomyelitis in sickle cell disease (approximately 50%), unlike the general population where S. aureus predominates. Reason: Splenic dysfunction (autosplenectomy) impairs clearance of encapsulated organisms and Salmonella. S. aureus is still the second most common. Clinical challenge: Differentiating bone infarction (vaso-occlusive crisis) from osteomyelitis - both present with fever, pain, and elevated inflammatory markers. MRI helps differentiate (osteomyelitis shows soft tissue abscess, cortical destruction).
Exam Pearl
Q: What are the orthopaedic manifestations of sickle cell disease?
A: Avascular necrosis: Femoral head (most common - 10-30% of patients), humeral head, vertebral bodies; due to vaso-occlusive crisis affecting end-arterial blood supply. Osteomyelitis: Increased risk, Salmonella most common pathogen. Bone infarcts: Long bone diaphyses; may mimic osteomyelitis. Dactylitis ("hand-foot syndrome"): Painful swelling of hands/feet in infants - first manifestation of SCD. Growth disturbance: Vertebral end-plate collapse ("H-shaped" or "Lincoln log" vertebrae). Pathological fractures from weakened bone.
Exam Pearl
Q: How do you differentiate bone infarction from osteomyelitis in sickle cell disease?
A: Clinical overlap: Both cause pain, fever, swelling, elevated WBC/CRP/ESR. Favoring osteomyelitis: Localized warmth, erythema, soft tissue abscess, single bone involvement, persistent fever despite hydration/analgesia. Favoring infarction: Multiple bone involvement, symmetric, responds to hydration/pain management. Imaging: MRI - osteomyelitis shows soft tissue collection, cortical destruction, enhancing abscess; infarction shows serpentine enhancement pattern. Aspiration/biopsy: Definitive - culture positive in osteomyelitis. When in doubt, treat empirically for osteomyelitis covering Salmonella and S. aureus.
Exam Pearl
Q: What perioperative considerations are important in patients with sickle cell disease undergoing orthopaedic surgery?
A: Preoperative: Hematology consultation; consider preoperative transfusion to achieve HbS less than 30% and Hb 10g/dL (exchange transfusion if needed); optimize hydration. Intraoperative: Avoid hypoxia, acidosis, hypothermia, dehydration (all precipitate sickling); use supplemental oxygen; warm IV fluids; careful tourniquet use (controversial - limit time, ensure adequate oxygenation). Postoperative: Continue supplemental oxygen; aggressive pain management; early mobilization; incentive spirometry (prevent acute chest syndrome); maintain hydration. Higher risk of VTE, infection, and wound complications.
Exam Pearl
Q: What are the treatment options for avascular necrosis of the femoral head in sickle cell disease?
A: Treatment mirrors AVN from other causes but with specific considerations: Early stages (Ficat I-II): Protected weight-bearing, core decompression (mixed results in SCD). Advanced stages (Ficat III-IV): Total hip arthroplasty - higher complication rate in SCD (infection, wound problems, perioperative crisis) but outcomes improving with modern perioperative protocols. Specific considerations: Younger patient age often; higher revision rates than non-SCD; cement may be preferred (abnormal bone quality); aggressive perioperative transfusion reduces complications. Preoperative optimization critical.
SICKLE CELL DISEASE ORTHOPAEDIC
High-Yield Exam Summary
PATHOPHYSIOLOGY
- •HbS: Glu6Val mutation
- •Sickling under hypoxia/acidosis
- •Vaso-occlusion causes infarcts
- •Autosomal recessive
ORTHOPAEDIC ISSUES
- •AVN: Hip/shoulder, 10-50%
- •Osteomyelitis: SALMONELLA > Staph
- •Bone crises: Painful vaso-occlusion
- •H-shaped vertebrae: Endplate infarcts
PERIOPERATIVE (CHANT)
- •Cold avoidance
- •Hydration critical
- •Acidosis prevention
- •Normal oxygen (SpO2 95%+)
- •Transfuse: HbS less than 30%, Hb 10
THA OUTCOMES
- •Infection: 10-15%
- •Survivorship: 80-90% at 10yr
- •Higher revision rates
- •Counsel about complications