Sickle Cell Anemia

Notes
  • Sickle cell disease (SCD) is a genetic disorder that is caused by the presence of a mutated form of hemoglobin (hemoglobin S or HbS)
  • It occurs mainly in black people manifesting early in childhood.
  • In Kenya, SCD is common in Nyanza, Western, and Coastal regions
  • Statistics: 5% of the world’s population carries trait genes for HB disorders (sickle-cell disease and thalassemia); globally, 3.2 million people had SCD and 43 million had sickle-cell trait in 2013; about 80% of SCD occur in sub-Saharan Africa; in 2013, SCD related globally death were 176,000; 6-9 million infants are born with SCD in Africa annually affecting 3% of births; carrier frequency of sickle-cell trait in Kenya is 28-35%.

##Pathogenesis of SCD

  • Homozygous inheritance of HbS gene leads to HbS
  • In HbS, valine is substituted for glutamic acid in the 6th amino acid of the β chain.
  • After oxygenation, HbS becomes less soluble and forms a semisolid gel
  • The semisolid gel leads to deformation of RBCs into a sickle shape at sites of low oxygen pressure.
  • The sickle-shaped and inflexible RBCs adhere to vascular endothelium and plug small arterioles and capillaries leading to infarction.
  • The sickle cells are destroyed in the spleen
  • At the same time venous plugging predisposes the patient to thromboses
  • Also due to their fragility, the mechanical trauma of circulation causes them to hemolyze.
  • Bones are deformed as a result of chronic compensatory marrow hyperactivity.

## Sickle cell crisis (acute exacerbation of SCD)

  • There are 3 types of sickle cell crisis: thrombotic, aplastic and hemolytic
  • This crisis occurs as a result of ischemia and infarction of the bones (mostly), spleen, lungs, or kidneys.
  • There is often no known reason that triggers the sickle-cell crisis but occasionally it can be elicited by fever, viral infection, and local trauma.
  • One of the components of sickle-cell crisis is the aplastic crisis that occurs when marrow erythropoiesis slows during acute infection leading to acute erythroblastopenia.

##Patients who are heterozygous for HbS,

  • Do not experience hemolysis or sickle-cell crisis
  • They can be affected by exposure to severe hypoxic conditions and exercises
  • In case of severe and sustained exercises, rhabdomyolysis and sudden death can occur
  • Other problems that can occur include hyposthenuria (inability to concentrate urine), unilateral hematuria and typical renal papillary necrosis
Symptoms
  • Chronic, normocytic and hemolytic anemia
  • Life-threatening anemia with rapid enlargement of the spleen and high reticulocyte count (due to splenic sequestration of sickle cells)
  • Pain in any part of the body (that can be chronic or acute)
  • Severe abdominal pain with vomiting
  • Increased susceptibility to infections (especially bacterial infections)
  • Occlusion of major intracranial blood vessels that could lead to hemiplegia, cranial nerve palsies, and other neurological deficits
  • Retardation of growth and maturation
  • Underweight
  • Chronic and painful leg ulcers
  • Priapism
  • Bilateral painful and swollen hands and/or feet in children (Hand-foot syndrome)
  • Acute chest syndromes that may include sudden onset of fever, chest pain, leukocytosis and pulmonary infiltrate
  • Cholelithiasis
  • Stroke (and other CNS involvement)
  • Symptoms of renal disorders
  • Symptoms of heart failure (due to dilation of both ventricles and the left atrium)
  • Visual disorders that include ptosis (drooping of the upper eyelid), retinal vascular changes and proliferative retinitis
  • Pulmonary hypertension
  • Avascular necrosis of the femoral or humeral head as a result of vascular occlusion
  • Tower shaped (“bossing”) skull
  • Arthralgia with fever
Diagnosis
  • Clinical evaluation
  • CBC count with differential and reticulocyte count
  • Hemoglobin electrophoresis for HBS
  • Peripheral blood smear
  • DNA prenatal testing, sometimes
Differential
  • Septic arthritis
  • Gout
  • Acute abdomen
  • Osteomyelitis
  • Trauma
Prevention
  • Folic acid orally OD for life
  • Prophylactic antibiotics (Penicillin daily from birth to 5yrs)
  • Vaccination against various infectious diseases
Management
  • Folic acid orally OD for life
  • Penicillin daily from birth to 5yrs (as immune system is not fully developed)
  • Hydroxyurea
  • Blood transfusion (is occasionally required)

##Management of sickle cell crisis:

  • Administer fluids either IV or orally until dilute urine is produced
  • Pain management depending on severity. If very severe, administer Inj Morphine 10mg PRN
  • Treatment of bacterial infections with IV Ceftriaxone 1gm OD x 1/52 OR Co-amoxiclav 2gm TID x 1/52
  • Treat for Malaria , if in endemic area
  • Tabs Folic acid OD  (and DO NOT give Ferrous Sulphate or any iron
  • Blood transfusion [at the beginning of blood transfusion give IV furosemide 1mg/kg STAT, however, it should NOT be administered if the patient is bleeding]
  • If a patient has ≥ 3 crisis per year administer Tabs/caps Hydroxyurea (Hydoxycarbamide) 10mg/kg STAT then increase by 5mg/kg to 25mg/kg/day
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