Sickle cell disease is an autosomal recessive condition resulting in a substitution of a valine for glycine in the β-globin subunit of Hb, forming HbS. HbS is less soluble under reduced O2 tensions and leads to deformation of red blood cells (sickling) when deoxygenated (e.g. in atelectatic lung), resulting in chronic haemolysis and vascular occlusion with tissue infarction in individuals homozygous for the β-globin gene mutation (sickle cell anaemia/disease). Hb electrophoresis or high-performance liquid chromatography (HPLC) in sickle cell disease demonstrates HbS ~80–99% and no normal Hb HbA; anaemia Hb 6–9g/dL is usual. Heterozygote carriers of the β-globin gene mutation are referred to as having ‘sickle cell trait’ and are largely asymptomatic, although sickle crises may occur during extreme hypoxia (e.g. during anaesthesia); HPLC analysis demonstrates HbS ~35–40%, and HbA (normal Hb) ~50%. Sickle Hb solubility testing does not distinguish between trait and homozygous disease.
• Pneumonia is more common, particularly from Chlamydia pneumoniae, S. pneumoniae, H. influenzae, Mycoplasma, Legionella, and respiratory viruses; may precipitate acute chest syndrome. Invasive pneumococcal disease is significantly more common. Patients should take lifelong prophylactic penicillin, as functionally asplenic
• Asthma appears to be a common comorbidity and may be associated with increased vaso-occlusive crises and episodes of acute chest syndrome
• Nocturnal oxyhaemoglobin desaturation is common, pathogenesis unclear—tonsillar hypertrophy is common, and OSA may be a contributing factor
• Pulmonary thromboembolism appears to be more common and may precipitate acute chest syndrome
• Sickle cell chronic lung disease is a poorly described entity, characterized by progressive breathlessness and abnormal pulmonary function, sometimes with PHT. Thought to follow recurrent episodes of lung infarction/infection, although there may not be a history of previous acute chest syndrome. Radiologically, characterized by multifocal interstitial infiltrate. PFTs typically restrictive, although airways obstruction also described
• PHT is a relatively common complication of sickle cell disease and other forms of haemolytic anaemia. Management is largely as for IPAH in a specialist centre (see p. [link]). Hydroxyurea and transfusions reduce episodes of vaso-occlusive crisis and acute chest syndrome and may be of benefit. Inhaled NO may have a role; studies are ongoing. A minority of these patients have CTEPH.
Definition and clinical features
Defined as a new pulmonary infiltrate on CXR, consistent with consolidation but not atelectasis, typically associated with symptoms such as fever, cough, chest pain, and breathlessness. A form of acute lung injury, which may progress to ARDS. One of the leading causes of death in sickle cell disease, although mortality has fallen due to use of maintenance hydroxyurea therapy and earlier treatment with transfusion. Risk factors include young age, high steady state leucocyte counts and Hb levels, smoking, and past history of acute chest syndrome. May follow surgery and anaesthesia.
may not be apparent and include one or more of infection (including viruses, atypical bacteria, encapsulated bacteria, MRSA), pulmonary fat embolism (preceded by bony pain), in situ thrombosis or PE, atelectasis following hypoventilation (from acute painful crisis of chest wall or excessive opiates), and possibly pulmonary oedema due to excessive hydration. Each leads to hypoxia with increased sickling and vascular occlusion, and initially mild disease can escalate rapidly to ARDS and death. All patients with a painful vaso-occlusive crisis should be monitored closely for the development of the acute chest syndrome; routine use of incentive spirometry may help prevent its development in these patients.
• Blood tests Raised WCC, anaemia; check HbS %
• Hypoxia is common and may be underestimated using pulse oximetry; A–a gradient predicts clinical severity; consider ICU transfer if worsens
• Culture blood and sputum
• CXR shows multifocal pulmonary infiltrates, sometimes with pleural effusion
• BAL may be considered in patients not responding to treatment
• Echo reveals evidence of PHT and right heart strain in a significant minority of patients, associated with a higher mortality; such patients may also develop excessive haemolysis and thrombocytopenia and may benefit from a more aggressive exchange transfusion policy.
Supportive care on ICU may be required. Liaise with haematology team. Treatment comprises:
• O2 to correct hypoxia; monitor ABGs
• Empirical broad-spectrum antibiotics (including a macrolide)
• Rehydration (IV fluids may be needed; care to avoid overhydration)
• Bronchodilators are often used; airflow obstruction is common, may contribute to high airway pressures during mechanical ventilation
• Ensure adequate analgesia for bony pain (consider NSAIDs; IM or SC opiates often required)
• Incentive spirometry and chest physiotherapy to prevent atelectasis. Pain may limit their use, and CPAP may be better tolerated
• Simple and exchange blood transfusion both reduce the HbS concentration and improve oxygenation in acute chest syndrome, and early transfusion therapy is recommended. Simple transfusion is indicated if anaemic with Hb <10g/dL, although Hb should not be raised above 11g/dL, as the increase in blood viscosity exacerbates sickling. Exchange transfusion should be used in patients with a relatively high Hb, aiming for HbS <20%, and is also recommended in severe or rapidly progressive disease
• Other treatments Successful use of inhaled NO for the treatment of a handful of refractory cases has been reported, but a clinical trial has failed to demonstrate a reduction in the development of acute chest syndrome following treatment of vaso-occlusive crises with NO. Corticosteroids may be of benefit in reducing length of hospital admission, but rebound painful crises are more common, and routine use of corticosteroids is not usually recommended. Hydroxycarbamide increases foetal Hb and reduces sickling and significantly reduces the incidence of acute chest syndrome; it is recommended for patients with recurrent episodes.
~13% of patients with acute chest syndrome require mechanical ventilation; overall mortality 4–9%.