Day 12, Lecture 1: Clinical Correlation 3: Sickle Cell

Question 1

Normal cells vs. Sickle Red cells

Answer 1

Question 2

Sickle Cell incidence in the USA

Answer 2

• 1 in 13 african americans carries the trait
• 1 in 365 African Americans has sickle cell disease
• Prevalence in US is approximately 100,000

Question 3

What causes Sickle cell

Answer 3

• Inherited disorder
• A missense mutation in the Beta subunit of (A to T) leads the substitution of a Valine for a glutamic acid. This causes polymerization
  
  • The cells are normal in their oxygenated state but when the cells are deoxygenated they polymerize together

Question 4

What factors increase Polymerization of Sickle cells

Answer 4

• Increased Temperature
• Acidosis
• Dehydration
• Deoxygenation of RBC (i.e. distance from pulmonary bed)
• Absence of other normal hemoglobins (e.g. Hgb A, Hgb F)

Question 5

Sickle Cell Pathology

Answer 5

• Blockage of small capillaries by sickle cells
• Endothelial activation and damage
• Adherence of WBC to Endothelium
• Platelet and coagulation factor activation

Question 6

Sickle cell laboratory features

Answer 6

• Hemolytic Anemia
  
  • low baseline hemoglobin (7-10g/dL)
  • Elevated reticulocyte count
  • Hyperbilirubinemia
  • Increased Lactate Dehydrogenase
• Elevated WBC (decreased margination)
• Elevated platelets (decreased splenic function)

Question 7

Possible Sickle Cell Genotypes

Answer 7

• Hgb AS (sickle cell trait)
• Hgb SS (sickle cell disease-SS, Sickle cell anemia)
• Hgb SC (sickle cell disease-SC)
• Hgb Sbeta thalassemia
• Hgb S/other e.g. SE, SG, SO,SD

Question 8

Sickle Cell Pain

Answer 8

• Caused by ischemia or infarction of bone
• May occur at any site
• Often has a typical location
• may have swelling and warmth at site or have no physical findings other than pain
• No lab test will tell if the pt is having pain
  
  • ​Hgb, bilirubin, % of sickled cells on smear do not change from baseline values in most vaso-occlusive crises. Xray and MRI often not helpful

Question 9

Treatment of Vaso-occlusive Pain

Answer 9

• Local heat
  
  • ​(no ice packs)
• hydration
• combination of medications works better
  
  • NSAIDS
  • Opioids
• Non-pharm therapy
• Always consider other possible causes
  
  • Conditions that anyone can have
    
    • Appendicitis or gastroenteritis
  • Sickle Cell Specific conditions
    
    • Osteomyelitis or gallstones

Question 10

Strategies to Prevent Death form infection in sickle cell patients

Answer 10

Question 11

Acute chest sydrome Definition

Answer 11

• A new infiltrate on CXR accompanied by at least one of the following
  
  • Chest pain
  • Fever
  • Hypoxia
  • Respiratory Distress
    
    • (SOB, Wheezing, cough)
• (note tha thsi is the second most common reason for sickel cell hospital admission)

Question 12

Risk factors for Stroke in Sickle Cell patients

Answer 12

• Prior symptoms (TIAs)
• Low steady state hemoglobin
• High WBC
• High blood pressure
• Recent Acute Chest Syndrome
• Abnormal Transcranial Doppler

Question 13

Treatment of Stroke in Sickle cell patients

Answer 13

• Acute
  
  • Exchange transfusion to decrease Hgb S to <30%
  • Rehabilitation if necessary
• Chronic
  
  • Chronic Transfusion to prevent production of Sickle cells (keep Hgb S about 30%)- indefinite duration
    
    • Decreases the incidence of 2nd storke form 50-90% to <10%
    • Chelation therpay to prevent iron overload is necessary with the chronic transfusions
• Prevention
  
  • Transcranial Doppler screening

Question 14

Life expectancy in Sickle Cell disease

Answer 14

• Median Age of Survival (mid 1990s)
  
  • Sickle cell disease-SS
    
    • 40-45 years
  • Sickle Cell-disease-SC
    
    • 60-65 years

Question 15

New Sickle Cell Disease Strategies

Answer 15

• Drugs to promote Hgb F
  
  • e.g. Hydroxyurea
    
    • Chemotherpay agent commonly used to treat chronic leukemia
    • Dose limiting toxicity is myelosupression
      
      • thus you must watch for dropping WBCs
  • Azacitidine
• Stem Cell Transplant
• Gene Transfer Therapy
  
  • gene addition
    
    • Anti-sickling beta-globin vector
    • Gamma-globin vector
  • leads to reactivation of fetal hemoglobin