Advances in the use of plasma exchange and adjunctive therapies have defined a new standard of care for thrombotic thrombocytopenic purpura (TTP), which was typically fatal for patients prior to the gradual introduction of therapeutic plasma infusion beginning in the late 1970s.1

TTP is a thrombotic microangiopathy wherein patients experience a severe deficit in ADAMTS13, the protease that cleaves von Willebrand factor (VWF). The deficiency allows the accumulation of large VWF multimers, and in the microvasculature, these multimers change conformation due to shear stress, promoting platelet adhesion and the formation of microthrombi. The resulting occlusions may cause ischemic damage to every organ, but the brain, heart, and digestive tract appear to be affected the most.1,2

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TTP may be congenital; however, acquired immune-mediated TTP (iTTP) represents more than 95% of cases, which often necessitate emergency treatment due to the severity of presentation. Formerly known as Moschcowitz syndrome, iTTP involves the production of autoantibodies against ADAMTS13. Approximately half of iTTP cases are associated with a preexisting autoimmune disease, HIV infection, or pregnancy; the autoimmune process may also be initiated by other precipitating factors.1,3

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In a review published in Expert Review of Hematology, Adrien Picod, MD, and Paul Coppo, MD, PhD, both of the Hôpitaux de Paris in France, described recent developments in iTTP treatment and how health care professionals can best assist patients who experience this life-threatening disease.1

“In the past 50 years, the gradual understanding of iTTP pathophysiology and treatment refinement has translated into a dramatic improvement of the once-dismal prognosis of the disease, from almost always fatal to almost always curable,” said Dr Picod in a statement to Hematology Advisor.

Management of iTTP consists of 3 axes that should be implemented as soon as possible after the onset of symptoms:

  • Emergency ADAMTS13 supplementation via therapeutic plasma exchange (TPE)
  • Inhibition of platelet-VWF interaction using caplacizumab
  • Immunosuppression with frontline rituximab and corticosteroids

“The key to improving prognosis now is early presumptive diagnosis (helped with clinical scores) and early treatment,” said Dr Picod.

Because ADAMTS13 activity may take days to determine, clinical scores, such as the French Score and the PLASMIC score, have been created to determine the probability of TTP in order to assist in presumptive diagnosis.1,4,5


“Nowadays, iTTP represents a category 1 indication for TPE according to the American Society for Apheresis,” wrote the authors. “TPE should be initiated as soon as presumptive diagnosis of iTTP is made, without waiting [for] the result of ADAMTS13 activity measurement, because any delay is associated with worse prognosis.”

During therapeutic plasma exchange for iTTP, patient plasma is extracted via plasmapheresis and replaced by an equal volume of fresh frozen plasma, and centrifugation plasmapheresis or membrane filtration plasmapheresis is used to separate the whole blood into its constituent components.1