Sickle Cell Disease
last authored: Oct 2009, Dave LaPierre
last reviewed:
Introduction
Sickle cell disease is a genetic condition affecting hemoglobin and leading to anemia. There are different subtypes, each each differences in type and severity of disease. Ranging from most severe to least severe, they are: SS, SC, sickle cell thalassemia, and SD disease.
The Case of...
a simple case introducing clincial presentation and calling for a differential diagnosis. To get students thinking.
Causes and Risk Factors
Sickle cell diseases are inherited, with an increased incidence in people from African and Mediterranean descent. It is thought that being a carrier of the disease prevents malaria pathogenicity.
Numerous mutations have been identified. Some of the more common include:
- HbS - Glu6 is substituted to Val6
- HbC - Glu6 is substituted to Lys6
- HbD -
Pathophysiology
Mutated hemoglobin leads to polyfibre formation in the deoxy state and reduced solubility. RBCs sickle under stress conditions, including low pO2, dehydration, fever, and acidosis.
Symptoms arise from intravascular sickling, capillary occlusion, thrombosis, and infarction. Organs most commonly affected include the spleen, lungs, bones, brain, and digits.
Hemolysis leads to a chronic normochromic, normocytic anemia, with Hgb in the 60-90 g/L range.
Signs and Symptoms
Symptoms begin after 5-6 months, following the fall in fetal Hb levels.
vaso-occlusive crisis - fever and pain
- dactylitis
- long bones of arms and legs
- priapism
acute chest crisis: fever, chest pain, progressive respiratory distress, pulmonary edema
acute splenic sequestration: splenomegaly, abdominal pain, tender spleen, shock
signs and symptoms of anemia (fatigue, tachycardia, headache, etc) can be chronic.
Investigations
- lab investigations
- diagnostic imaging
Lab Investigations
Screening is often carried out for high-risk infants.
First molecularly diagnosed disease.
Can be diagnosed using Western blotting, as Hb C and S move slower than Hb A.
DNA can be examined using RFLPs or ASOs.
Fetal diagnosis
Microscopic hematuria may be the only evidence in people with SC trait.
Diagnostic Imaging
Differential Diagnosis
Management
Acute crises require admission for supportive treatment.
This includes fluids, analgesia, antibiotics, oxygen, and incentive spirometry.
Transfusions should be given if significant anemia or chest crisis is evolving.
RBC exchange transfusion if stroke is impending, chest crisis is severe, or priapism is persistent.
Chronic management includes:
- early, aggressive treatment of infection, along with prophylactic antibiotics
- vaccination for penumococcus, meningiococcus, hepatitis B, Hib, and influenza
- folate supplementation PRN
- hydroxyurea if disease severe
- chonic transfusion regimen if history of stroke
- genetic counselling
- annual ophthalmologic exam after 10 years
- referral to hematology
Consequences and Course
Splenic dysfunction begins after age 5 following repeated infarction. This leads to increased susceptibility to encapsulated bacteria (ie S. pneumoniae, H. influenzae, meningococcus).
Increased risk of osteomyelitis, especially Salmonella, occurs. other ramifications include growth delay, bony amnormalities, gallstones, retinopathy, and restrictive lung disease.
Resources and References
Topic Development
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