Sickle cell disease
Obviously, in most circumstances the patient would be able to inform the medical team that they have a history of sickle cell disease – but to make this case interesting – the diagnosis was not revealed immediately!!!
Approximately 0.15% of African American children are homozygous for the sickle cell gene, and 8% have sickle cell trait.
This autosomal recessive disorder is characterized by a single amino acid substitution (glutamic acid to valine) in the beta subunits of the hemoglobin tetrameric protein.
Upon deoxygenation, hemoglobin S undergoes conformational changes that expose a hydrophobic region surrounding the valine moiety in the beta-subunit. Polymerization with other hemoglobin tetramers occurs with the formation of long polymer chains that ultimately distort the erythrocyte membrane
Hemoglobin S molecules aggregate upon deoxygenation to form polymer nuclei that become the seeds for further polymerization. In sickle red cells, hemoglobin S polymerizes as the cells traverse the microvasculature.
Factors that increase the intracellular concentration of hemoglobin (red blood cell dehydration), that increase time spent in the microcirculation (increased expression of adhesion molecules), or deoxygenation of hemoglobin, all contribute to increased polymerization.
Increased levels of non-S hemoglobins such as fetal hemoglobin (hemoglobin F) or hemoglobin A2 slow the rate of polymerization and reduce intracellular polymer content at any oxygen saturation. As polymer content increases, the red cell becomes increasingly rigid, retarding transit through the microvasculature.
HPLC – High performance liquid chromatography
SICKLE CELL DISEASE
Pulmonary disease, manifested as the acute chest syndrome (ACS), is a common complication of sickle cell anemia, accounting for 25% of premature deaths
- Bone infarction (rib, sternum and vertebra) leading to atelectasis and regional hypoxia. (incentive spirometry reduces basal atelectasis)
- Fat emboli – bone marrow embolisation
- Microvascular in situ thrombosis – increased adherence of erythrocytes to endothelial cells.
- Thromboembolic disease
- Vascular injury and inflammation – endothelin-1 levels are elevated during vaso-occlusive crisis.
- fever (80%)
- cough (74%)
- chest pain (57%)
- dyspnea (28%)
- productive cough (24%)
- hypoxia (mean PaO2 of 71 mm Hg)
- infiltrates on chest radiographs – often progressed to multilobar pulmonary disease indistinguishable from the acute respiratory distress syndrome.
- serial chest x-rays
- Pulse oximetry monitoring
- Physiotherapy – incentive spirometry
- Involvement of HDU/ITU team
- To confirm diagnosis – blood film and HPLC – the blood film in this case showed – sickle cell, target cell, howell jolly body, pappenheimer bodies and nucleated red cells.
The role of transfusion support is not clearly defined. Transfusing one to two units when there is a need for increased oxygen binding capacity can be beneficial – i.e. moderate to severe anaemia, high cardiac output, easy fatigability.
Transfusion risks in sickle cell disease
- transmission of viral disease
- acute hyperviscosity
Exchange transfusion – should be given promptly if there is evidence of clinical deterioration. Exchange transfusion has the obvious benefit of replacing sickle cells with normal cells and preventing further sickling induced damage to the lungs or other organs, while providing better oxygen carrying capacity. The indications for exchange transfusion in the ACS have not been fully defined but include poor pulmonary function as evidenced by:
- arterial oxygen saturation (SaO2) persistently less than 80% despite aggressive ventilatory support
- serial decline in SaO2
- unstable &/or worsening vital signs
- persistent respiratory rate greater than 30/minute
MARK T. GLADWIN, ALAN N. SCHECHTER, JAMES H. SHELHAMER, and FREDERICK P. OGNIBENE “The Acute Chest Syndrome in Sickle Cell Disease”, American Journal of Respiratory and Critical Care Medicine, Vol. 159, No. 5 (1999), pp. 1368-1376
How I treat acute chest syndrome in children with sickle cell disease Scott T. Miller. Published online before print March 15, 2011, doi: 10.1182/blood-2010-11-261834