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08 Lessons from ITP: treatment of refractory thrombocytopenia
  1. Sacha Zeerleder
  1. University Hospital (Inselspital), Bern, Switzerland


Immune thrombocytopenia (ITP) is an acquired bleeding disorder caused by both increased platelet destruction and decreased platelet production. The pathophysiology of ITP is complex: a loss of immune tolerance due to, among others, Th1-skewing and reduction of regulatory T-cell activity finally resulting in the production of autoreactive T- and B cells. Platelets targeted by autoantibodies are removed by macrophages in the spleen and liver through the Fc-gamma receptor, which activation is controlled by the spleen tyrosine kinase (SYK). Finally, autoantibodies and cytotoxic T-cells may suppress platelet production in the bone marrow.1

Although in many cases ITP is a primary disease, it may occur as a secondary condition associated with infection, drugs, autoimmune diseases, immunodeficiencies and malignancy. ITP is a diagnosis of exclusion and response to treatment may confirm diagnosis.2 3 Therapy should be started in patients with active bleeding or asymptomatic patients with platelet counts below 30 × 10E9/L. In asymptomatic patients with platelet counts around 30 × 10E9/L or higher, initiation of treatment should carefully be weighted with the individual risk of bleeding determined by age and co-morbidities. 3 First-line treatment of ITP consist of high-dose steroids and occasionally, or especially in case of bleeding, intravenous gammaglobulins. When there is inadequate or no response to first-line therapy second-line therapy is indicated. Second-line therapy includes thrombopoietin-receptor agonists, B-cell depletion therapy, immunomodulation with intravenous gammaglobulins, immunosuppressive agents (e.g. azathioprine, cyclosporine, mycophenolate mofetil) and SYK inhibitors (such as fostamatinib).1–3 Although still considered an effective treatment, splenectomy is less frequently applied as a second-line treatment, since the availability of effective pharmaceutical agents, the potential complications of splenectomy and the inability to predict on whether patients do respond to splenectomy. After several ITP treatment have been applied with no or only minimal response the diagnosis of ITP has to be reconsidered. In this case the presence of bone marrow failure syndromes, myelodysplastic syndrome or inherited thrombocytopenias must be excluded.2

Learning Objectives

  • Explain the pathophysiology of ITP

  • Describe how to make the diagnosis of ITP and when to reconsider diagnosis

  • Discuss the therapeutic options for refractory ITP


  1. Cooper N, Ghanima W. Immune Thrombocytopenia. N Engl J Med. 2019;381(10):945–55.

  2. Miltiadous O, Hou M, Bussel JB. Identifying and treating refractory ITP: difficulty in diagnosis and role of combination treatment. Blood. 2020;135(7):472–90.

  3. Neunert C, Terrell DR, Arnold DM, et al.American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829–66.

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