Sickle Cell Anemia

Etiology of sickle disease and its effects on organs

  • Sickle cell disease is an autosomal recessive disease (need to be homozygous recessive) that results from a single AA substitution resulting in hemoglobin S
  • RBCs that contain sickle cell hemoglobin only lives for 20 days (rather than 120 for normal RBCs), they eventually become hard and damage membranes
    • When the sickle cells become hard, they impair circulation, destroy RBCs & causes stasis of blood flow
  • Sickle cell is often identified via neonatal screening with most complications occurring prior to 8 years of age  (may often be asymptomatic however until exacerbated by exercise, extreme conditions, etc
  • Lab findings:  increased reticulocytes, unconjugated bilirubin, LDH & fetal hemoglobin.  The Hgb/Hct ratio however will be decreased
  • Clinical findings:  vaso-occlusion, hemolysis, organ damage
  • Organs affected:  spleen, brain (stroke), kidneys, liver, lungs, eyes, etc
  • Splenic sequestration crisis is caused by vaso-occlusion & results in splenomegaly & a rapid drop in HgB & often times requires elective splenectomy
  • An aplastic crisis may result from the transient arrest of erythropoiesis
  • Severe pain crisis:  often is the first symptom sickle cell patients will present with.  It affects the chest, back, abdomen & extremities most frequently & may last for days or weeks.  Pain is directly correlated with high HgB levels & is precipitated by weather, stress, dehydration, etc
    • Treatment:  NSAIDs, APAP w/ codiene can be used outpatient for mild-moderate, whereas opioids are typically reserved for severe pain inpatient
      • There is a problem with suboptimal pain control & a lack of treatment for chronic pain.  Patients may also develop either tolerance or hyperanalgesia
  • Acute chest syndrome:  lung involvement may result from pneumonia, infarctions/emboli .  It’s seen in 30-50% of patients & has a high rate of mortality.
    • Treatment:  aggressive
  • Stroke risk is the highest for kids 2-5 & some kids have silent lesions so a transcranial doppler should be used routinely to screen for these (from age 2-16).  Kids should also get routine eye exams
    • Treatment:  infusion therapy
  • Infection is a major cause of morbidity & mortality in patients with sickle cell disease
    • Kids often are more often affected by encapsulated bacteria (S. Pneumoniae & H. influenzae)
    • Adults are more often affected by E. Coli, S. Aureus, & Salmonella
  • Prego–may cause spontaneous abortions, intrauterine growth restriction, low birth weight, acute chest syndrome, infections & DVTs in the mother

Prophylaxis with certain drugs can reduce death and the incidence of sickle cell crisis

  • Supportive treatment:
    • immunizations (especially pneumococcal, influenza, meningococcal, Hep B)
    • Pen Vk 125-250 mg BID:  given from 3 months to at least 5 years of age
      • May get Erythromycin 20 mg/kg/day if allergic
    • folic acid 1 mg/day–used to accelerate erythropoiesis  (megaloblastic anemia = FA deficient anemia)
      • Should also give vitamins B12 & B6
    • fetal hemoglobin inducers (HYDROXYUREA, butyrate, decitabine) help to decrease RBC sickling  (increase HbF & thus decrease HbS production)
      • HYDROXYUREA– is FDA approved to prevent painful crisis & decreases mortality, hospitalizations & need for transfusions.  Delays the progression of organ dysfunction.
    • chronic transfusion therapy–is lifesaving for acute illness.  It helps to prevent strokes & other organ damage.  Done every 3-4 weeks to reduce HbS to < 30% of total hemoglobin.
      • Risks of transfusion:  alloimmunization, infections, Fe overload
  • Allogenic stem cell transplant–curative
    • In order to qualify for this, the patient must be younger than 16, have severe complications of pain or stroke & have a HLA-matched donor
    • Risks:  GVHD, secondary malignancies

Role of transfusions, pain management and antibiotics in the sickle cell patient

  • General approach to acute complications:  treat the cause if you can identify one & provide supportive care
    • Supportive care:  begin analgesic-drug therapy, replace fluids & ensure adequate oxygen saturation
  • Treatment of sickle cell crisis:
    • Hydration:  fluid replacement (may be up to 3-4 L)
    • Pain:  morphine or hydromorphone
    • Antibiotics, transfusion (if pt has hypoxia, acute chest syndrome or stroke) & a workup to determine infectious complications & stroke
      • Patients at high risk for sepsis should receive ceftriaxone, clindamycin (if the pt has a PCN allergy), vanco or a macrolide

FYI:  sickle cell is an autosomal recessive disease (not sex linked), HgS causes problems with circulation & clottting, opioids & hydration are essential to managing sickle cell crises, prevention of complications includes use folic acid, vaccines & PCN, stem cell transplantation is the only cure & Fe overload is a problem in pts receiving chronic transfusions

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