Hemolytic Uremic Syndrome (HUS)

Summary

HUS, or hemolytic uremic syndrome, is a disorder characterized by hemolysis and uremia. HUS is caused by shiga-like toxins created by the EHEC bacteria. The toxins cause excessive cytokine release into the circulation, which leads to damage of the walls of blood vessels. Widespread damage to blood vessels leads to the formation of microthrombi, small aggregates of platelets that can block blood flow. Clinically, HUS most commonly affects young children. The consumption of platelets to form microthrombi leads to thrombocytopenia. These microthrombi in small vessels can shear passing red blood cells to induce hemolysis, in what is formally known as microangiopathic hemolytic anemia, or MAHA for short. Microthrombi can also block flow to the small vessels of the kidney, leading to acute kidney injury. Other symptoms to look out for include mucocutaneous bleeding and a history of bloody diarrhea. On laboratory testing, patients with HUS will usually have decreased platelet and red blood cell counts and increased bleeding times. Schistocytes may be seen on peripheral blood smear.

Key Points

• Hemolytic Uremic Syndrome (HUS)
  • Pathogenesis
    • Commonly caused by shiga-like toxin from EHEC (serotype O157:H7) infection
      • Cytokine release damages endothelium → microthrombi formation → consumption of platelets → microthrombi cause mechanical shearing RBCs intravascularly
    • Atypical form (aHUS) is caused by complement gene mutations or autoimmune response
  • Presentation
    • Classically seen in children
      • Most commonly affected by E. coli infections
    • Triad of:
      • Thrombocytopenia
      • Microangiopathic hemolytic anemia (MAHA)
      • Acute kidney injury
    • No fever or neurologic symptoms
      • In contrast to TTP
    • History of bloody diarrhea
      • Associated with EHEC or Shigella
    • Mucocutaneous bleeding
      • Gingival bleeding, menorrhagia, petechiae, epistaxis
  • Diagnosis
    • Decreased platelet count
      • Due to consumptive microthrombi
    • Hemolytic anemia
      • Microthrombi adhesion can shear and damage RBCS
      • Schistocytes seen on peripheral smear
      • Elevated LDH
    • Increased bleeding time
      • Due to decreased platelet count
    • Normal PT/PTT
      • Helps distinguish vs. DIC
  • Treatment
    • Supportive care
      • Fluids to maintain kidney perfusion
      • 3-5% mortality