Thrombotic Thrombocytopenic Purpura (TTP)

Summary

TTP, short for thrombotic thrombocytopenic purpura, is a platelet disorder caused by auto-antibodies targeting an important enzyme called ADAMTS13. ADAMTS13 normally functions to break down vWF, so when ADAMTS13 is inhibited, a buildup of vWF results. This buildup of VWF in turn causes platelet plugs to form all over the body, which can get stuck into small blood vessels as microthrombi. Epidemiologically, this disease primarily affects young women. Clinically, excessive consumption of platelets into microthrombi causes a decrease in functioning platelets or thrombocytopenia. What’s more, microthrombi in small vessels can destroy red blood cells as they squeeze past, causing microangiopathic hemolytic anemia, or MAHA. These sheared red blood cells can be visualized as schistocytes on peripheral blood smears.  What’s more, these microthrombi can block blood flow to small vessels in organs, leading to acute kidney injury and neurological dysfunction. Fever and systemic inflammation are often seen in patients. Lastly, the decrease in functioning platelets leads to signs of mucocutaneous bleeding. Apart from reduced red blood cell and platelet counts on laboratory testing, increased bleeding times are also seen. TTP can be treated through repeated plasma exchange.

Key Points

• hrombotic Thrombocytopenic Purpura (TTP)
  • Pathogenesis
    • Inhibition of ADAMTS13
      • Usually by autoantibody
      • ADAMTS is a metalloprotease enzyme that usually works to break down vWF
      • Impaired degradation of vWF → vWF multimers buildup → platelet aggregation → microthrombi formation → mechanical shearing of RBCs intravascularly
      • May require a secondary trigger (e.g. SLE, drugs)
  • Presentation
    • Typically affects young adult women
      • Due to autoimmune nature
    • Pentad of:
      • Thrombocytopenia
      • Microangiopathic hemolytic anemia (MAHA)
      • Acute kidney injury
        • Less common than in HUS
      • Fever
        • Not commonly seen with HUS
      • Neurologic symptoms (e.g. confusion)
        • Not seen in HUS
    • 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
    • Plasmapheresis (plasma exchange)
      • Life-saving therapy
    • Steroids
    • Rituximab