Sickle Cell Disease

Question 1

Etiology

Answer 1

Mutation of chromosome 11 that substitutes a Glu–>Val on the beta chains causing RBCs to sickle (Hgb S)

Question 2

Pathophysiology

Answer 2

Sickled RBCs

• 10-20 days (compared to 120 day nl)
• May fluctuate between sickle <–> nl, must be in the normal biconcave disc form to enter capillaries. Vasoocclusion results when it sickles in post-capillary venules

The roads that lead to vascular occlusion are (generally)

• infection/inflammation
• hypoxia/acidosis
• dehydration

These lead to:

• RBC’s/RBCs are stickier - more adhesion to endothelium
• hypercoagulability
• increased platelets

Question 3

Newborn Screenings

Answer 3

**Important to educate families **

• educating about the disease - pain is the biggest issue –> can turn into crisis (strokes or acute chest syndrome)
• Bacterial sepsis from splenic failure –>can be dead in 6 hrs so need to bring kids in fast (now vaccinate against s. pneumo)
• acute splenic sequestration crisis –> hypovolemic shock because cell sickle and can’t escape (exsanguinate internally)

By education patients, survival improved

Question 4

Hemoglobin F Therapy

Answer 4

Hydroxyurea

• Chemotherapy agent, but no fertility issues or other risks
• increases Hgb F
• nitric oxide donor –> vasodilation
• adhesion alteration
• anticoagulation
• arginine increases - precursor for NO

Very effective drug, but many pts have mistrust in doctors so difficult to get them to get pts on.

Question 5

Stroke Prevention

Answer 5

Also at risk for stroke

• Use doppler US to screen for blockages (increase in noise of blood flow)
• If present, 95% will have stroke
• May be prevented with chronic blood transfusions (now looking at transitioning to hydroxyurea)

Question 6

Pulmonary HTN Screening

Answer 6

Pulm HTN leading cause of death from sickle cell disease

Common and serious in adults and children with sickle cell disease

Pathogenesis: hemolysis (because RBCs lyse more quickly –> hgb binds NO and destroys arginine), dysregulated arginine metabolism (leading to dec’d NO), hypoxia, thrombosis, asplenia

Use doppler echocardiography to screen for, beginning at age 10

Improves with hydroxyurea tx

Question 7

Oral Iron Chelation

Answer 7

Important because when constant transfusions - can get iron toxicity.

Products: Desperol shots, Exjade, Ferriprox (PO)

Approved for pts >2yrs

Arthralgias - Can be painful, agranulocytosis.

Question 8

Bone marrow transplantation

Answer 8

Balance how much of bone marrow have to wipe out

Use depends on prognosis and families

Can potentially have worse complications from BMT than symptoms from sickle cell disease

BUT… only cure for sickle cell disease

Question 9

Gene therapy

Answer 9

Use HIV to insert a promotor for Hgb F - being used so far in thalassemia