Immune Thrombocytopenia (ITP)

Malattie Delle Piastrine

  • Immune Thrombocytopenia (ITP)



  1. 1. Pathogenesis
  2. 2. Clinical manifestations
  3. 3. Diagnosis
  4. 4. Treatment and prognosis


Immune thrombocytopenia (ITP) is an autoimmune disorder that affects patients of all ages, gender and races and that was known as Idiopathic thrombocytopenic purpura. An International Working Group (IWG) on ITP recently recommended that this disease be designated Immune thrombocytopenia because this terminology identifies the immune pathogenesis of ITP and because patients with ITP may not exhibit purpura or bleeding manifestations. (1)  ( Blood 2009 vol. 113 pp. 2386-2393)  ITP  can be  primary with a platelet count < 100,000 mcL in the absence of other causes or disorders that may be associated with thrombocytopenia, or secondary to other autoimmune disorders, chronic infections such as Helicobater pylori or Hepatitis C, vaccines, lymphoproliferative disorders, and drugs. ITP of 3 to 12 months duration is designated as persistent ITP , whereas chronic ITP is defined as disease of more than 12 months duration. In this disease antiplatelet glycoprotein antibodies cause thrombocytopenia reducing the survival of circulating platelets and inhibiting the production of new platelets by bone marrow megakaryocytes. Specific IgG autoantibodies by B cells are most often directed against platelet membrane GPIIb-IIIa and to a less extent against GPIb-IX or other platelet GPs. (2)  (British Journal of Haematology 2011 vol. 152 pp. 52-60)  Like many other autoimmune diseases, ITP has a T helper cell type 1 bias and a reduced activity of T-regulatory cells. Cytotoxic T cells may directly lyse platelets and possibly suppress megakaryopoiesis.(3)  (Seminars in Thrombosis and Haemostasis 2012 vol. 38 pp. 454-462) The diagnosis of primary ITP is one of exclusion considering nonimmune causes of thrombocytopenia and secondary ITP.  The first line therapy for ITP include corticosteroids, sometimes in conjuction with intravenous immunoglobulin or anti-rhesus D. Second line therapy may include rituximab or splenectomy, deciding case by case and, as third line therapy, thrombopoietin receptor agonists. There is no consensus on which of these drugs is superior and no controlled data to support the use of one rather than the other, and although splenectomy provides the greatest chance for long-term remission, this surgical procedure presents an increased risk of venous thromboembolism and sepsis in patients with ITP and its use is declining. (4)  (Blood 2013 vol. 121 (23) pp. 4782-4790)
Incidence was 2.9/100,000 person-years, with peaks among children and in those > 60 years of age. Persistence of chronicity occurred in 36% of children compared with 67% of adults. Among adults, 18% of ITPs were secondary. Malignancy was the main cause (10.9%). Myelodysplastic syndromes were not rare (2.3%). Severe gastrointestinal or central nervous system bleeding at ITP onset was rare (< 1%). (5) (Blood 2014 vol. 124 (22) pp. 3308-3315) 
Interestingly, some investigators showed that antiplatelet antibodies detected by the Monoclonal-Specific Immobilization of Platelet Antigens (MAIPA) assay in patients with newly diagnosed immune thrombocytopenia are associated with chronic outcome and higher risk of bleeding. (6) (Annals of Hematology 2014 vol. 93 pp. 309-315)  See section on "Treatment and prognosis". A well done study was published recently in March 2015, in which Kapur and collegues show that C-reactive protein, a ligand for Fc receptors on phagocytes, increases antibody-mediated platelet destruction by human phagocytes in vitro and in vivo mice. Without platelet antibodies, CRP was found to be inert toward platelets, but it bound to phosphorylcholine exposed after oxidation triggered by antiplatelets antibodies, thereby enhancing platelets phagocytosis. CRP levels are increased in ITP patients and correlate with platelet counts and bleeding severity and predict time to recovery. CRP amplifies antibody-mediated platelet destruction and may in part explain the aggravation of thrombocytopenia on infections. The authors conclude with the observation that targeting C-Reactive Protein (CRP) could offer new therapeutic opportunities for these patients. (7) (Blood 2015 vol. 125 (11) pp. 1793-1802)  For details, see section on "Pathogenesis".  

References  :

1 )  Rodeghiero F., Stasi R., Gernsheimer T., et al.  :  Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children : report from an international working group. Blood 2009; 113 : 2386-2393
2 ) Toltl Lisa J. and Arnold Donald M.  : Pathophysiology and management of chronic immune thrombocytopenia : focusing on what matters. British Journal of Haematology 2011; 152 : 52-60
3 ) Stasi Roberto :  Immune thrombocytopenia : Pathophysiologic and clinical update. Seminars in Thrombosis and Haemostasis 2012; 38 : 454-462
4 ) Boyle Soames, White Richard H., Brunson Ann et al.  : Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia. Blood 2013; 121 (23) : 4782-4790
5 ) Moulis Guillame, Palmaro Aurore, Montastruc Jean-Louis et al.  : Epidemiology of incident immune thrombocytopenia : a nation wide population-based study in France. Blood 2014; 124 (22) : 3308-3315   
6 ) Kapur Rick, Heitink-Pollé Katja M.J., Porcelijn Leendert et al.  : C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia. Blood 2015; 125 (11) : 1793-1802