Sickle Cell Disease

last authored: Oct 2009, Dave LaPierre

 

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.

return to top

 

 

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:

return to top

 

 

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.

 

return to top

 

 

Signs and Symptoms

Symptoms begin after 5-6 months, following the fall in fetal Hb levels.

 

vaso-occlusive crisis - fever and pain

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.

return to top

 

 

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

return to top

 

 

Differential Diagnosis

return to top

 

 

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:

return to top

 

 

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.

 

return to top

 

 

The Case of...

Case #2 - a small story wrapping it all up and asking about esp management.

return to top

 

 

Additional Resources

return to top

 

 

Topic Development

created:

authors:

editors:

reviewers:

 

return to top