Sickle cell anemia

Sickle Cell Anemia Overview

• Characteristics: Sickle cell anemia involves abnormally shaped red blood cells—specifically, crescent or sickle-shaped.

  • First identified in 1910.

• Symptoms:

  • Hemolytic Anemia: Caused by excessive degradation of red blood cells, resulting in reduced counts.

  • Vaso-occlusive Crises: Blockages in blood vessels due to sickled cells, slowing blood flow.

  • Results in reduced oxygen delivery to organs (tissue ischemia).

  • Common symptoms include:

    • Fatigue

    • Dizziness

    • Weakness (due to reduced oxygen)

    • Iron deficiency from hemolysis

    • Shortness of breath

    • Chronic pain from vaso-occlusive episodes, especially in bones and joints

    • Pale skin (due to low red blood cell count)

    • Jaundice (from excessive bilirubin due to hemolysis)

    • Swelling in extremities (due to poor circulation)

    • Vision problems and headaches (from reduced oxygen delivery)

Complications of Sickle Cell Anemia

• Acute complications include:

  • Myocardial infarction (heart attack)

  • Stroke

  • Acute chest syndrome (blockages in lungs)

• Long-term complications may involve:

  • Vision loss (due to lung tissue damage)

  • Kidney failure (from damage and excessive proteins in urine)

  • Liver damage (due to processing excessive bilirubin)

  • Bone tissue damage from red blood cell production impacts.

Evolutionary Perspective

• Sickle cell anemia is a recessive disorder, leading to high fatality rates, yet persists in populations due to malaria resistance.

• Origins: Likely originated in Central West Africa, with both isolated groups and admixture contributing to its spread.

• Sickle cell trait provides resistance to malaria, showcasing balancing selection where the trait persists despite its negative health impacts.

Importance of Evolutionary Studies

• Studying evolutionary history aids in understanding population genetics and the inheritance of genetic conditions.

• This research compiles evidence for the malaria hypothesis:

  • High sickle cell disease prevalence in malaria-prevalent regions demonstrates evolutionary benefits.

Prevalence and Genetics

• Global prevalence: 1 in 893 affected, 1 in 302 (African descent).

• Sickle Cell Disease vs. Sickle Cell Anemia: Sickle cell anemia is the most severe form and accounts for 63% of sickle cell disease cases.

• Genetic Inheritance: Sickle cell anemia is autosomal recessive due to mutations in the hemoglobin beta gene on chromosome 11.

• Mutation Details:

  • A single base pair mutation at the sixth codon changes glutamic acid to valine, altering hemoglobin properties.

  • This mutation reduces oxygen binding capacity and causes red blood cells to become rigid and sickled.

Effects of Sickle Cell Anemia

• Altered hemoglobin leads to:

  • Sickled red blood cell structure: sticky and rigid, causing reduced circulation.

  • Increased hemolysis results in lower red blood cell counts and higher bilirubin levels.

Sickle Cell Disorders

• Encompasses various hemoglobin mutations.

• Co-inheritance examples:

  • Hemoglobin SC: Milder symptoms when sickle trait coexists with abnormal allele.

  • Hemoglobin E and H disorders also exhibit varying symptoms.

  • Alpha thalassemia as a negative interaction reducing malaria resistance.

Genetic Testing

• Blood tests measure hemoglobin S protein levels.

• Prenatal diagnostics include amniotic fluid and placenta samples from 8-10 weeks.

• Heel prick tests for newborns check for hemoglobin abnormalities.

Treatment Options

• Varies with severity:

  • Pain medications and blood transfusions during crises.

  • Hydroxyurea: increases fetal hemoglobin, improving cell flexibility and reducing sickling.

• Other approved treatments:

  • L-glutamine and prisanlizumab help manage symptoms and complications.

  • Hydration is crucial to prevent crises; patients need to drink 8-10 cups of water daily.

• Crises Treatment: Emergency care involves pain relief, hydration, transfusions, and hydroxyurea for preventative measures.

Research Insights

• Long-term hydroxyurea studies show reduced vaso-occlusive events and mortality.

• Genetic variability affects patient responses to hydroxyurea, influenced by inherited factors.