Pulmonary Complications of
Sickle Cell Disease
Tygerberg Children`s Hospital
Sickle Cell Disease
• Caused by the inheritance of 2 copies of a
mutant beta-globin gene – 1 from each parent.
• Mutation = GAG GTG at position 6 in beta-
globin chain of HbA HbS
• One of the most common inherited autosomal
recessive disorders in the world.
• Certain areas in sub-Saharan Africa – 40-60% of
population heterozygote 1-4% of babies born
• HbS polymerises on deoxygenation
rigidity of erythrocyte, distorts its shape &
causes structural damage in red cell
• Altered rheologic properties of cell impairs
blood flow through microvasculature
haemolysis &vaso-occlusive episodes.
• Pulmonary complications of SCD in
children remain leading cause of morbidity
What does the literature say?
• 2 recent articles on Pulmonary
complications of (SCD)
• Recurrent episodes of severe pain in SCD
• Caused by microvascular entrapment of
RBC & WBC obstruction in blood flow &
• Microvascular events episodes of
explosive pain & inflammation.
• May be accompanied by fever &
leukocytosis +/- bone marrow necrosis
with pulmonary emboli.
The Acute Chest Syndrome (ACS)
• Common form of lung injury in SCD
• When severe analogous to acute respiratory
• Defined by development of new pulmonary
infiltrates consistent with alveolar consolidation
but not atelectasis involving at least one
• Radiographic abnormality accompanied by chest
pain, fever, tachypnoea, wheezing or cough.
Causes of Acute Chest Syndrome
• 3 major causes proposed:
1. pulmonary infection
2. embolisation of bone marrow fat – ffg
3. intravascular pulmonary sequestration
of sickled erythrocytes lung injury &
Clinical aspects of ACS
• Associated with marked systemic
inflammation, fever, leukocytosis , abrupt
drop in Hb and thrombocytopaenia.
• May require ventilatory support
• Rapid simple or exchange blood
transfusion, removes sickled erythrocytes
Pulmonary Complications of SCD
• Acute chest syndrome
• Asthma (airway hyperreactivity)
• Chronic sickle lung disease
• Pulmonary hypertension
• Sleep disordered breathing
• Significant comorbidity in children with
• Chronic lung dx can also occur – probably
result of recurrent episodes of ACS
• High incidence of airway hyperreactivity in
• However, low prevelance of asthma – may
• Children with SCD and asthma have nearly
twice as many episodes of ACS.
• Several theories: VQ mismatch local tissue
hypoxia and increased sickling of RBC, increase
release of inflammatory markers may cause
increase airway hyperreactivity.
• Further studies warranted to determine if
aggressive Rx of asthma reduces risk of ACS
and possibly morbidity & mortality of ACS in
• Prevalence of pulmonary hypertension in
children with SCD similar to that in adults (+/-
• Defined as pulmonary artery systolic pressure:
greater than 35mmHg (mild)
greater than 45mmHg (mod-
• Tricuspid regurgitation velocity jet over
2.5m/s(mild) or 3.5m/s (mod-severe)
Calculating pulmonary artery
• Pulmonary artery pressure assumed to =
right ventricular(RV) systolic pressure.
• RV systolic pressure estimated from
Bernoulli principle = as a fluid jet increases
velocity, its lateral pressure is reduced.
Pathophysiology of pulmonary
• Mulitiple mechanisms:
- Left ventricular dysfunction from chronic
- Lung damaging infarctions
- Recurrent pneumonia & ACS
- Recent interest – role of nitric oxide,
decreased NO bioavailability pulmonary
Rx of Pulmonary HPT
• Information on Rx remains anecdotal.
• Sildenafil use studied.
• Arginine – substrate of NO shown to reduce
pulmonary artery pressure in SCD
• Other agents: prostacycline, bosentan
(endothelin receptor blocker)
• Blood transfusion – lowers plasma Hb by
reducing hemolysis & suppressing
hematopoesis of Hb sickle cells lower
pulmonary artery pressures.
Sleep disordered breathing
• Children with SCD have increased risk of
SDB and abnormal ventilation during
• 36% of children with SCD have SDB
• Poor sleep quality associated with pain and VOC
as well as nocturnal oxyhaemoglobin
• Upper airway obstruction – increased risk of
obstructive sleep apnoea – thought to be due to
compensatory lymphoid hyperplasia of tonsil
and adenoids following splenic infarction.
Significant reduction in symptoms ffg
Postulated reasons cont..
• Correlation between SDB and elevated cerebral
blood flow velocity (CBFV) in children with SCD.
• Measured with transcranial doppler ultrasound.
• Related to cerebral artery stenosis, severe
anaemia & tissue hypoxia.
• Association between elevated CBFV & UAO.
Adenotonsillectomy can normalisation of
CBFV and prevention of adverse neurological
• Pulmonary dx remains an important cause
of morbidity & mortality in children with
• Pulmonary complications can interact with
each other amplifying the adverse effects.
• Further research needed to evaluate these