Sickle Cell Disease

Congenital haemoglobinopathy leading to production of the relatively insoluble haemoglobin S, causing erythrocytes to adopt a ‘sickle’ shape under conditions of physiologic stress. Sickle cell anaemia leads to:

Epidemiology and Risk Factors

Pathophysiology

Autosomal recessive:

  • Homozyogotes have sickle cell disease
    • Chronic haemolytic anaemia
    • Recurrent vaso-occlusion and severe pain
    • Progressive organ damage
    • Often early death
  • Heterozygotes have sickle cell trait
    • Results in HbS levels of ~30-40%
    • HbS may precipitate in conditions of physiologic stress
    • Usually well

HbS:

  • Work normally when oxygenated
  • Deforms in hypoxia, resulting in polymerisation and deformation of the red cell into a sickle shape
    Sickled cells:
    • Are rigid and sticky
      Can obstruct capillary flow, leading to vaso-occlusion.
    • Haemolyse rapidly
      Lifespan of 10-20 days
      • Leads to anaemia due to rapid turnover

Aetiology

Clinical Manifestations

Sickle cell anaemia may present as a series of different crises.

Vasoocclusive crisis:

  • Sudden onset pain
    Ischaemia or infarction secondary to microvascular obstruction.
  • Hypovolaemia
    Inability to concentrate urine.
    • Generally hypernatraemic, and require volume resuscitation with hypotonic solutions

Sequestration crisis:

  • Pooling of erythrocytes in spleen and liver
    Presents as:
    • Anaemia
    • Hypovolaemic shock

Assessment

History:

Exam:

Investigations

Bedside:

Laboratory:

  • Blood
    • FBE
      • Chronic anaemia
    • Hb electrophoresis
      For diagnosis.
    • Blood film:
      • Sickle forms
      • Reticulocytosis
    • Sickledex test:
      • Rapid screening
      • Qualitative detection of HbS levels >10%
Sickle Cell

Imaging:

Other:

Diagnostic Approach and DDx

Management

  • Prevent and treat sickling precipitants
  • Transfusion

Resuscitation:

Specific therapy:

  • Pharmacological
    • Vaccination
      If asplenic.
  • Procedural
    • Bone marrow transplantation
      Usually restricted to <16 year olds.
    • Exchange transfusion
      May be required for severe vasoocclusive crises.
  • Physical

Asplenism is covered under Asplenia.

Supportive care:

  • H
    • Hb >50

Disposition:

Other:

Prevention:

  • Avoid precipitants
    • Dehydration
      • Exercise
      • Hot weather
      • Alcohol
    • Hypoxia
      • Smoking
      • OSA
    • Physiological stress
    • Hypothermia
  • Folic acid supplementation
  • Hydroxyurea
    ↑ HbF formation, and so reduces frequency and severity of vaso-occlusive crises.

Medical

Surgical

Anaesthetic Considerations

Avoid precipitants of vaso-occlusive crises:

  • Hypoxia
  • Acidosis
  • Hypercapnoea
  • B
    • PHTN
  • C
    • CCF
    • Volume state
      • Minimise fasting period
      • Preoperative hydration
    • Avoid venous stasis
  • E
    • Tourniquet use
      • May precipitate sickle crisis distal to tourniquet
      • Careful exsanguination of distal limb prior to inflation
  • H
    • Sickle cell severity
      • Frequency of exacerbations
    • Hb
      • Should be transfused to Hb >100g/dL or HbS <30%

Marginal and Ineffective Therapies

Complications

  • B
    • Pulmonary hypertension
      Recurrent pulmonary infarction.
  • C
    • Cardiac failure
  • D
    • TIAs/CVAs
  • H
    • Functional asplenism
      Consequential lymphoid hypertrophy.

Prognosis

Key Studies

References

  1. Wilson M, Forsyth P, Whiteside J. Haemoglobinopathy and sickle cell disease. Contin Educ Anaesth Crit Care Pain. 2010;10(1):24-28. doi:10.1093/bjaceaccp/mkp038