成人原发免疫性血小板减少症诊治中国专家共识(2012修订版)解读知识讲稿.ppt

Estimated annual rate of bleeding according to age group Oligoclonal expansions of GP-specific CD4+T cells Fogarty PF, et al. Clin Adv Hematol Oncol 2003;1:365-71 T-cell activation in ITP Semple et al. Blood 1991;78:2619-25 Semple et al. Blood 1996;87:4245-54 Lost of T-cell tolerance to self antigen in ITP Peng，et al. Blood 2003；101：2721-26 Zhang，et al. J Thrombosis Haemostasis 2007；6:158–65 Disturbed apoptosis of T cells Olsson, et al. Thromb Haemost 2005;93:139-44 Loss of T-cell tolerance 发病机制 对自身抗原免疫耐受缺失 血小板生成减少 血小板破坏增多 Platelet production is suboptimal in ITP patients Autologous 111In-platelet studies show platelet production≤ normal in 2/3 patients TPO levels normal in 75% of ITP patients (relative TPO deficiency) Autoantibodies inhibit both Mk growth and Mk apoptosis Trail-mediated megakaryocyte para-apoptosis leading to in vitro dysmegakaryocytopoiesis and impaired platelet production Thrombopoietin levels in ITP patients ????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????? ? ? ?? Hou et al. Br J Haematol 1998;101:420-4 Decreased platelet production Trail-mediated megakaryocyte para-apoptosis leading to in vitro dysmegakaryocytopoiesis plasma antibody Removal of antibody The number of megakaryocytes Megakaryocyte apoptosis Antibodies inhibit the Generation of megakaryocytes Yang, et al. Blood 2010;116:4307-16 发病机制 对自身抗原免疫耐受缺失 血小板生成减少 血小板破坏增多 Increased platelet destruction Autoantibody-mediated platelet clearance Zucker-Franklin, et al. N Engl J Med 1977;297:517-23 CTL-mediated platelet lysis Olsson, et al. Nat Med 2003;9:1123-27 GPIbα desialyation leading to platelet apoptosis Heyu Ni, et al. JCI. 2013 on published GPIbα desialyation Kupffer cell PLT PLT Increased platelet destruction Chow, et al. Blood 2010;115:1247-53 GPIIIa knockout mice Immunized with platelets CD19(+) Splenocytes CD8(+) Spleno