We have discussed many medical “myths” previously (ex, Atropine for RSI, Cuffed ETTs, ORT vs IVF, Morphine for Appendicitis), but recently one of my esteemed PEM Fellows enlightened me about another.  We have touched on some of the complications that must be considered with Sickle Cell Disease (ex, Splenic Sequestration, Acute Chest Syndrome, Cholelithiasis, Sepsis), but had not spent time on Sickle Cell Trait, because it is thought of as a “benign” condition.  Fortunately, Dr. JR Young taught me differently. So let us look at the complications associated with Sickle Cell Trait.

Sickle Cell Trait

• Sickle Cell Trait = inheritance of one normal hemoglobin gene (HgA) and one sickle hemoglobin gene (HgS).
• It is estimated that Sickle Cell Trait affects ~ 300 million people worldwide. [Tsaras, 2009]

• HgS leads to red blood cell sickling and polymerization under certain circumstances:
  • Tissue Hypoxia
  • Acidosis
  • Dehydration
  • Increased Viscosity
  • Hypothermia
• The severity of sickling is lower in individuals with lower HgS concentrations.

Sickle Cell Trait: Benign?

• Sickle Cell Trait is commonly considered benign and protective.
  • Benign:
    • Have similar hemoglobin / hematocrit levels as those without a hemoglobinopathy
    • Similar life expectancy
    • Able to donate blood similar to others
  • Protective:
    • Sickle Cell Trait confers protection against falciparum malaria.
    • It does not protect against other malarias (Plasmodium vivid, Plasmodium oval, or Plasmodium malaria).

• Complications associated with Sickle Cell Trait are relatively rare, but, importantly, do occur. [Chapa-Rodriguez, 2015; Khan, 2014]

Sickle Cell Trait: Complications

• Hematuria
  • Most frequent complication [Tsaras, 2009]
  • Both microscopic and macroscopic is seen. [Chapa-Rodriguez, 2015; Khan, 2014]
  • ~50% of cases are due to renal papillary necrosis.
  • Kidneys promote sickling: [Alvarez, 2015]
    • Renal medulla has low partial oxygen pressure
    • It is hypertonic and acidotic, which both encourage sickling.
    • Leads to microinfarctions in the renal medulla

• Renal Medullary Cancer
  • Rare, but aggressive, malignant tumor
  • First described in 1995 (so our understanding of its epidemiology is nascent)
  • 217 cases known of to date  [Alvarez, 2015]
  • Almost exclusively seen in Young patients with Sickle Cell Trait
    • Median age = 22 years
    • Range = 5 – 69 years
    • 88% of cases occurred in patients with Sickle Cell Trait
  • Presents commonly with flank/abdominal pain and/or hematuria.
  • Median survival is 15 weeks.

• Splenic Infarction
  • More common in setting of low oxygen tension at high altitudes. (See NFL Players and Denver story)
  • Most cases are mild, but may lead to Acute Splenic Syndrome – Severe Pain, Splenomegaly, and LUQ tenderness.
  • Splenic Rupture may occur.

• Hyposthenuria
  • Hyposthenuria = relative inability to concentrate urine.
  • Due to repetitive microinfarctions (Again, kidney’s and sickle hemoglobin don’t like each other).
  • Leads to loss of free water.
  • Likely contributes to exertion-related illness and death.
    • Exertional Rhabomyolysis
    • Heat Stroke
    • Exertional-related Sudden Death

Moral of the Morsel

• Sickle Cell Trait confers its own unique complications – the concept of sickle cell trait being benign is a myth.
• Hematuria in a patient with sickle cell trait deserves attention.
  • Is this renal stone?
  • Is this renal papillary necrosis?
  • Or… is the the rare, yet particularly lethal Renal Medullary Cancer?

References