Pulmonary Complications of Sickle Cell Disease

1
Pulmonary Complications of Sickle Cell Disease

• Aneesa Vanker
• Respiratory Meeting
• 17-03-2009
• Tygerberg Childrens Hospital

2
Sickle Cell Disease(SCD)

• 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
  have disease.

3

• HbS polymerises on deoxygenation ? rigidity of
  erythrocyte, distorts its shape causes
  structural damage in red cell membrane.
• Altered rheologic properties of cell impairs
  blood flow through microvasculature ? haemolysis
  vaso-occlusive episodes.

4
Pulmonary Complications

• Pulmonary complications of SCD in children remain
  leading cause of morbidity and mortality.

5
What does the literature say?

• 2 recent articles on Pulmonary complications of
  (SCD)

6
(No Transcript)
7
Vaso-occlusive crises

• Recurrent episodes of severe pain in SCD
• Caused by microvascular entrapment of RBC WBC ?
  obstruction in blood flow organ ischaemia
• Microvascular events ? episodes of explosive pain
  inflammation.
• May be accompanied by fever leukocytosis /-
  bone marrow necrosis with pulmonary emboli.

8
(No Transcript)
9
The Acute Chest Syndrome (ACS)

• Common form of lung injury in SCD
• When severe analogous to acute respiratory
  distress syndrome.
• Defined by development of new pulmonary
  infiltrates consistent with alveolar
  consolidation but not atelectasis involving at
  least one segment.
• Radiographic abnormality accompanied by chest
  pain, fever, tachypnoea, wheezing or cough.

10
Causes of Acute Chest Syndrome

• 3 major causes proposed
• 1. pulmonary infection
• 2. embolisation of bone marrow fat ffg
  vaso-occlusive crisis
• 3. intravascular pulmonary sequestration of
  sickled erythrocytes ?lung injury infarction

11
(No Transcript)
12
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 ? rapid recovery.

13
Pulmonary Complications of SCD in children

• Acute chest syndrome
• Asthma (airway hyperreactivity)
• Chronic sickle lung disease
• Pulmonary hypertension
• Sleep disordered breathing

14
Asthma

• Significant comorbidity in children with SCD
• Chronic lung dx can also occur probably result
  of recurrent episodes of ACS
• High incidence of airway hyperreactivity in
  several studies
• However, low prevelance of asthma may be
  underdiagnosed

15
(No Transcript)
16

• 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 SCD

17
(No Transcript)
18
Pulmonary Hypertension

• Prevalence of pulmonary hypertension in children
  with SCD similar to that in adults (/- 33)
• Defined as pulmonary artery systolic pressure
  greater than 35mmHg (mild)
• greater than 45mmHg (mod-
  severe)
• OR
• Tricuspid regurgitation velocity jet over
  2.5m/s(mild) or 3.5m/s (mod-severe)

19
Calculating pulmonary artery pressure

• 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.

20
(No Transcript)
21
(No Transcript)
22
Pathophysiology of pulmonary hypertension

• Mulitiple mechanisms
• - Left ventricular dysfunction from chronic
  anaemia
• - Lung damaging infarctions
• - Recurrent pneumonia ACS
• - Recent interest role of nitric oxide,
  decreased NO bioavailability ? pulmonary
  vasoconstriction.

23
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.

24
Sleep disordered breathing(SDB)

• Children with SCD have increased risk of SDB and
  abnormal ventilation during sleep.
• 36 of children with SCD have SDB

25
Postulated reasons

• Poor sleep quality associated with pain and VOC
  as well as nocturnal oxyhaemoglobin
  desaturations.
• 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
  adenotonsillectomy

26
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 events.

27
(No Transcript)
28
Conclusion

• Pulmonary dx remains an important cause of
  morbidity mortality in children with SCD.
• Pulmonary complications can interact with each
  other amplifying the adverse effects.
• Further research needed to evaluate these
  relationships.

29
(No Transcript)