TTP – Treatment Overview

Overview of treatment of thrombotic thrombocytopenic purpura (TTP):

Pathophysiological basis for treatment:

  • von Willebrand factor (vWF) normally promotes interactions between platelets and the blood vessel wall.
  • vWF circulates as multimers of varying size; the largest of these multimers (called ultra-large multimers) are the most functionally (hemostatically) active.
  • Normally, the protease ADAMTS13, which is synthesized by the liver, cleaves circulating ultra-large vWF multimers, preventing excessive platelet-vessel wall interactions.
  • Immune TTP is caused by antibody-mediated reduction in ADAMTS13 levels.
  • ADAMTS13 deficiency results in excessive ultra-large vWF multimers, leading to uncontrolled platelet activation, adhesion and aggregation, microvascular thrombosis and tissue ischemia.

Treatment approaches:

  • Remove antibodies against ADAMTS13 – therapeutic plasma exchange (TPE) – the mainstay of treatment
  • Replenish ADAMTS13 – TPE
  • Block von Willebrand factor-platelet interactions – caplacizumab
  • Inhibit production of antibodies against ADAMTS 13 – corticosteroids, rituximab