Thrombotic Thrombocytopenic Purpura (TTP)

TTP is a form of Thrombotic Microangiopathy (TMA) associated with severe deficiencies of an enzyme called ADAMTS13 (say it like this: “Adam Tee Ess 13”). This enzyme is responsible for the trimming of von Willebrand Factor (vWF) from the large initial forms present when the protein first enters the bloodstream into smaller fragments. If the enzyme is severely deficient or absent (usually because of an autoantibody, but sometimes from birth), vWF doesn’t get trimmed into smaller sizes, and we are left with great big “multimers” of vWF (there is even a funny-sounding name for them: “Ultra-large von Willebrand Factor Multimers,” or “ULvWF multimers”). Platelets LOVE to bind to ULvWF multimers, and that binding results in formation of extensive, abnormal small aggregates/clots (“microthrombi”). The microthrombi damage red blood cells as they try to squeeze by, and this may lead to the classic “pentad” of diagnostic criteria for TTP:

  • Fever
  • Thrombocytopenia
  • Microangiopathic Hemolytic Anemia (“MAHA,” with schistocytes in the peripheral smear and lab evidence of intravascular hemolysis)
  • Renal failure
  • Mental status changes

However, according to the 2013 and 2016 American Society for Apheresis Guidelines, you don’t need to wait for all five, as “…the clinical findings of unexplained thrombocytopenia and MAHA are sufficient to diagnose TTP” (Schwartz J et al, “Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Sixth Special Issue” J Clin Apher 2013;28:145–284). This means that it is not only a mistake to wait until all five parts of the “pentad” are present to initiate therapy, but that waiting the often one week or so turnaround time for ADAMTS13 levels to confirm the diagnosis is another very big mistake. Therapeutic plasma exchange (with plasma replacement rather than albumin) is the treatment of choice, and should be initiated early and continued daily until the platelet count rises to above 150,000/mcL.

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