PNH 5/9/16

  • Check out this excellent AAFP review of Hemolytic Anemia!
  • Hemolytic anemias can be framed as Congenital and Acquired
    • Congenital: Sickle Cell, Thalassemia, G6PD, Spherocytosis
    • Acquired: PNH, MAHA, Infections, Immune.  Further categorization of Immune HA:
      • Autoimmune: Warm (ie SLE) or Cold (ie Mycoplasma)
      • Alloimmune (ABO incompatibility)
      • Drug-Induced: Many drugs but classically 3/4th general cephalosporins
  • Hemolysis labs include Reticulocyte Count, Indirect bilirubin levels, Haptoglobin, LDH, hemoglobinurea, hemosiderinuria (elevated Hb on urine dipstick is an indicator of intravascular rather than extravascular hemolysis)
  •  PNH median age of onset is 30, life expectancy prior to Eculuzimab (see below) was about 10-15 years after diagnosis although this new drug may prolong life expectancy but it’s too early to know
  • Acute hemolytic events can occur after stress, infections, alcohol use
  • PNH is associated with venous and/or arterial thrombosis (venous more common) likely due to the hypercoagulable state from free hemoglobin in the bloodstream. The thrombi form in unusual areas – cerebral veins and abdominal veins.
  • Other clinical findings associated with PNH are cytopenias, smooth muscle dystonias (due to lack of NO, erectile dysfunction/dysphagia/abdominal pain)
  • Nocturnal hemolysis is thought to be due to intestinal absorption of LPS, a complement activator, at night
  • The pathophysiology of PNH is an acquired mutation causing lack of formation of phosphatidyllinositol (PGI) anchor on RBCS which present the CD59 and CD55 epitopes. Flow cytometry in PNH shows a lack of CD59 and CD55 cells. The lack of these markers causes the cells to be vulnerable to complement mediated lysis.
  • Eculuzimab blocks complement C5 thereby blocking destruction of RBCs. Patients on this medication are at risk for infections due to encapsulated organisms (ie Strep Pneumo, Neisseria meningitidis, Haemophilus influenza etc). Note this drug is 10,000 bucks a pop (infusion every 2 weeks)!

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