4,892
Views
40
CrossRef citations to date
0
Altmetric
IMMUNE THROMBOCYTOPENIA

Advances in the pathophysiology of primary immune thrombocytopenia

&

References

  • Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, 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(11):2386–93.
  • Hayter SM, Cook MC. Updated assessment of the prevalence, spectrum and case definition of autoimmune disease. Autoimmun Rev. 2012;11(10):754–65.
  • Frederiksen H, Schmidt K. The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood. 1999;94(3):909–13.
  • Neylon AJ, Saunders PWG, Howard MR, Proctor SJ, Taylor PRA. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol. 2003;122(6):966–74.
  • Anon. Ferri consultor clinico, 2006–2007: claves diagnosticas y tratamiento. Available from: http://www.agapea.com/libros/Ferri-consultor-clinico-2006-2007-claves-diagnosticas-y-tratamiento-9788481749144-i.htm [Accessed March 13, 2014].
  • Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost JTH. 2006;4(11):2377–83.
  • Hedman A, Henter JI, Hedlund I, Elinder G. Prevalence and treatment of chronic idiopathic thrombocytopenic purpura of childhood in Sweden. Acta Paediatr Oslo Nor 1992. 1997;86(2):226–7.
  • Shulman NR, Weinrach RS, Libre EP, Andrews HL. The role of the reticuloendothelial system in the pathogenesis of idiopathic thrombocytopenic purpura. Trans Assoc Am Physicians. 1965;78:374–90.
  • Harrington WJ, Minnich V, Hollingsworth JW, Moore CV. Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura. J Lab Clin Med. 1951;38(1):1–10.
  • Shulman NR, Marder VJ, Weinrach RS. Similarities between known antiplatelet antibodies and the factor responsible for thrombocytopenia in idiopathic purpura. Physiologic, serologic and isotopic studies. Ann N Y Acad Sci. 1965;124(2):499–542.
  • Bartley TD, Bogenberger J, Hunt P, Li YS, Lu HS, Martin F, et al. Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl. Cell 1994;77(7):1117–24.
  • Kuter DJ, Beeler DL, Rosenberg RD. The purification of megapoietin: a physiological regulator of megakaryocyte growth and platelet production. Proc Natl Acad Sci USA. 1994;91(23):11104–8.
  • de Sauvage FJ, Hass PE, Spencer SD, Malloy BE, Gurney AL, Spencer SA, et al. Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature 1994;369(6481):533–8.
  • Lok S, Kaushansky K, Holly RD, Kuijper JL, Lofton-Day CE, Oort PJ, et al. Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. Nature 1994;369(6481):565–8.
  • Kaushansky K, Drachman JG. The molecular and cellular biology of thrombopoietin: the primary regulator of platelet production. Oncogene 2002;21(21):3359–67.
  • Wolber E-M, Jelkmann W. Thrombopoietin: the novel hepatic hormone. News Physiol Sci. 2002;17:6–10.
  • Li J, Xia Y, Kuter DJ. Interaction of thrombopoietin with the platelet c-mpl receptor in plasma: binding, internalization, stability and pharmacokinetics. Br J Haematol. 1999;106(2):345–56.
  • Kappers-Klunne MC, de Haan M, Struijk PC, van Vliet HHDM. Serum thrombopoietin levels in relation to disease status in patients with immune thrombocytopenic purpura. Br J Haematol. 2001;115(4):1004–6.
  • Ballem PJ, Segal GM, Stratton JR, Gernsheimer T, Adamson JW, Slichter SJ. Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance. J Clin Invest. 1987;80(1):33–40.
  • Emmons RV, Reid DM, Cohen RL, Meng G, Young NS, Dunbar CE, et al. Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction. Blood 1996;87(10):4068–71.
  • Kaushansky K. The molecular mechanisms that control thrombopoiesis. J Clin Invest. 2005;115(12):3339–47.
  • Houwerzijl EJ, Blom NR, van der Want JJL, Esselink MT, Koornstra JJ, Smit JW, et al. Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura. Blood 2004;103(2):500–6.
  • Semple JW, Freedman J. Increased antiplatelet T helper lymphocyte reactivity in patients with autoimmune thrombocytopenia. Blood 1991;78(10):2619–25.
  • Semple JW, Milev Y, Cosgrave D, Mody M, Hornstein A, Blanchette V, et al. Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura: relationship to platelet phenotype and antiplatelet T-cell reactivity. Blood 1996;87(10):4245–54.
  • Ogawara H, Handa H, Morita K, Hayakawa M, Kojima J, Amagai H, et al. High Th1/Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura. Eur J Haematol. 2003;71(4):283–8.
  • Kuwana M, Kaburaki J, Ikeda Y. Autoreactive T cells to platelet GPIIb-IIIa in immune thrombocytopenic purpura. Role in production of anti-platelet autoantibody. J Clin Invest. 1998;102(7):1393–402.
  • Olsson B, Andersson P-O, Jernås M, Jacobsson S, Carlsson B, Carlsson LMS, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003;9(9):1123–4.
  • Zhang F, Chu X, Wang L, Zhu Y, Li L, Ma D, et al. Cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura. Eur J Haematol. 2006;76(5):427–31.
  • Stasi R. Immune thrombocytopenia: pathophysiologic and clinical update. Semin Thromb Hemost. 2012;38(5):454–62.
  • Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010;115(2):168–86.
  • Sanz MÁ, Vicente García V, Fernández A, López MF, Grande C, Jarque I, et al. [Guidelines for diagnosis, treatment and monitoring of primary immune thrombocytopenia]. Med Clínica. 2012;138(6):261.e1–e17.
  • Neunert CE, Buchanan GR, Imbach P, Bolton-Maggs PHB, Bennett CM, Neufeld E, et al. Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group (ICIS). Blood 2013;121(22):4457–62.
  • McMillan R, Durette C. Long-term outcomes in adults with chronic ITP after splenectomy failure. Blood 2004;104(4):956–60.
  • Roitt I, Delves P. Roitt's essential immunology. 10th ed. Oxford: Wiley; 2001.
  • Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM. B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002;3(10):944–50.
  • Moulin V, Andris F, Thielemans K, Maliszewski C, Urbain J, Moser M. B lymphocytes regulate dendritic cell (DC) function in vivo: increased interleukin 12 production by DCs from B cell-deficient mice results in T helper cell type 1 deviation. J Exp Med. 2000;192(4):475–82.
  • Coutinho A, Caramalho I, Seixas E, Demengeot J. Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive or negative selection. Curr Top Microbiol Immunol. 2005;293:43–71.
  • Hsieh C-S, Lee H-M, Lio C-WJ. Selection of regulatory T cells in the thymus. Nat Rev Immunol. 2012;12(3):157–67.
  • Salinas GF, Braza F, Brouard S, Tak P-P, Baeten D. The role of B lymphocytes in the progression from autoimmunity to autoimmune disease. Clin Immunol Orlando Fla. 2013;146(1):34–45.
  • Zhang H-Y, Hou M, Zhang X-H, Guan X-H, Sun G-Z. The diagnostic value of platelet glycoprotein-specific autoantibody detection in idiopathic thrombocytopenic purpura. [Zhongguo Shi Yan Xue Ye Xue Za Zhi Zhongguo Bing Li Sheng Li Xue Hui] J Exp Hematol Chin Assoc Pathophysiol. 2004;12(2):204–6.
  • Roark JH, Bussel JB, Cines DB, Siegel DL. Genetic analysis of autoantibodies in idiopathic thrombocytopenic purpura reveals evidence of clonal expansion and somatic mutation. Blood 2002;100(4):1388–98.
  • McMillan R, Smith RS, Longmire RL, Yelenosky R, Reid RT, Craddock CG. Immunoglobulins associated with human platelets. Blood 1971;37(3):316–22.
  • Stahl CP, Zucker-Franklin D, McDonald TP. Incomplete antigenic cross-reactivity between platelets and megakaryocytes: relevance to ITP. Blood 1986;67(2):421–8.
  • Bettaieb A, Fromont P, Louache F, Oksenhendler E, Vainchenker W, Duédari N, et al. Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombocytopenic purpura. Blood 1992;80(1):162–9.
  • Wright JF, Blanchette VS, Wang H, Arya N, Petric M, Semple JW, et al. Characterization of platelet-reactive antibodies in children with varicella-associated acute immune thrombocytopenic purpura (ITP). Br J Haematol. 1996;95(1):145–52.
  • Quintana FJ, Cohen IR. The HSP60 immune system network. Trends Immunol. 2011;32(2):89–95.
  • Porges A, Bussel J, Kimberly R, Schulman I, Pollack M, Pandey J, et al. Elevation of platelet associated antibody levels in patients with chronic idiopathic thrombocytopenic purpura expressing the B8 and/or DR3 allotypes. Tissue Antigens. 1985;26(2):132–7.
  • Satoh T, Pandey JP, Okazaki Y, Yasuoka H, Kawakami Y, Ikeda Y, et al. Single nucleotide polymorphisms of the inflammatory cytokine genes in adults with chronic immune thrombocytopenic purpura. Br J Haematol. 2004;124(6):796–801.
  • Satoh T, Miyazaki K, Shimohira A, Amano N, Okazaki Y, Nishimoto T, et al. Fcγ receptor IIB gene polymorphism in adult Japanese patients with primary immune thrombocytopenia. Blood 2013;122(11):1991–2.
  • Pesmatzoglou M, Lourou M, Goulielmos GN, Stiakaki E. DNA methyltransferase 3B gene promoter and interleukin-1 receptor antagonist polymorphisms in childhood immune thrombocytopenia. Clin Dev Immunol. 2012;2012:352059.
  • Aslam R, Speck ER, Kim M, Crow AR, Bang KWA, Nestel FP, et al. Platelet Toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-alpha production in vivo. Blood 2006;107(2):637–41.
  • Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1(2):135–45.
  • Xu D, Liu H, Komai-Koma M. Direct and indirect role of Toll-like receptors in T cell mediated immunity. Cell Mol Immunol. 2004;1(4):239–46.
  • Akira S. Mammalian Toll-like receptors. Curr Opin Immunol. 2003;15(1):5–11.
  • Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol. 1994;12:991–1045.
  • Matzinger P. The danger model: a renewed sense of self. Science 2002;296(5566):301–5.
  • Semple JW, Aslam R, Kim M, Speck ER, Freedman J. Platelet-bound lipopolysaccharide enhances Fc receptor-mediated phagocytosis of IgG-opsonized platelets. Blood 2007;109(11):4803–5.
  • Yu H, Liu Y, Han J, Yang Z, Sheng W, Dai H, et al. TLR7 regulates dendritic cell-dependent B-cell responses through BlyS in immune thrombocytopenic purpura. Eur J Haematol. 2011;86(1):67–74.
  • Hoemberg M, Stahl D, Schlenke P, Sibrowski W, Pachmann U, Cassens U. The isotype of autoantibodies influences the phagocytosis of antibody-coated platelets in autoimmune thrombocytopenic purpura. Scand J Immunol. 2011;74(5):489–95.
  • Olsson B, Ridell B, Jernås M, Wadenvik H. Increased number of B-cells in the red pulp of the spleen in ITP. Ann Hematol. 2012;91(2):271–7.
  • Audia S, Samson M, Guy J, Janikashvili N, Fraszczak J, Trad M, et al. Immunologic effects of rituximab on the human spleen in immune thrombocytopenia. Blood 2011;118(16):4394–400.
  • Li X, Zhong H, Bao W, Boulad N, Evangelista J, Haider MA, et al. Defective regulatory B-cell compartment in patients with immune thrombocytopenia. Blood 2012;120(16):3318–25.
  • Blair PA, Noreña LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR, et al. CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity 2010;32(1):129–40.
  • Yazdanbakhsh K, Zhong H, Bao W. Immune dysregulation in immune thrombocytopenia (ITP). Semin Hematol. 2013;50(1):S63–7.
  • Amu S, Saunders SP, Kronenberg M, Mangan NE, Atzberger A, Fallon PG. Regulatory B cells prevent and reverse allergic airway inflammation via FoxP3-positive T regulatory cells in a murine model. J Allergy Clin Immunol. 2010;125(5):1114–24.e8.
  • Carter NA, Vasconcellos R, Rosser EC, Tulone C, Muñoz-Suano A, Kamanaka M, et al. Mice lacking endogenous IL-10-producing regulatory B cells develop exacerbated disease and present with an increased frequency of Th1/Th17 but a decrease in regulatory T cells. J Immunol Baltim Md 1950. 2011;186(10):5569–79.
  • Noh J, Choi WS, Noh G, Lee JH. Presence of Foxp3-expressing CD19(+)CD5(+) B cells in human peripheral blood mononuclear cells: human CD19(+)CD5(+)Foxp3(+) regulatory B cell (Breg). Immune Netw. 2010;10(6):247–9.
  • Guo Y, Zhang X, Qin M, Wang X. Changes in peripheral CD19(+)Foxp3(+) and CD19(+)TGFβ(+) regulatory B cell populations in rheumatoid arthritis patients with interstitial lung disease. J Thorac Dis. 2015;7(3):471–7.
  • Aslam R, Segel GB, Burack R, Spence SA, Speck ER, Guo L, et al. Splenic lymphocyte subtypes in immune thrombocytopenia: increased presence of a subtype of B-regulatory cells. Br J Haematol. 2016;173(1):159–60.
  • Zhong H, Bao W, Li X, Miller A, Seery C, Haq N, et al. CD16+ monocytes control T-cell subset development in immune thrombocytopenia. Blood 2012;120(16):3326–35.
  • Andersson P-O, Olsson A, Wadenvik H. Reduced transforming growth factor-beta1 production by mononuclear cells from patients with active chronic idiopathic thrombocytopenic purpura. Br J Haematol. 2002;116(4):862–7.
  • Liu H, Ouyang X, Li Y, Zeng H, Wang X, Xie S, et al. Involvement of levels of Toll like receptor-4 in monocytes, CD4+ T-lymphocyte subsets, and cytokines in patients with immune thrombocytopenic purpura. Thromb Res. 2013;132(2):196–201.
  • Rocha AMC, Souza C, Rocha GA, de Melo FF, Clementino NCD, Marino MCA, et al. The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia. Haematologica 2011;96(10):1560–4.
  • Saito A, Yokohama A, Osaki Y, Ogawa Y, Nakahashi H, Toyama K, et al. Circulating plasmacytoid dendritic cells in patients with primary and helicobacter pylori-associated immune thrombocytopenia. Eur J Haematol. 2012;88(4):340–9.
  • Chang D, Ouyang J, Zhou R, Xu J, Chen B, Yang Y, et al. [Profiles of different subsets of CD(4)(+) T cells in chronic idiopathic thrombocytopenic purpura]. Zhonghua Nei Ke Za Zhi. 2010;49(3):213–6.
  • Cao J, Chen C, Zeng L, Li L, Li X, Li Z, et al. Elevated plasma IL-22 levels correlated with Th1 and Th22 cells in patients with immune thrombocytopenia. Clin Immunol Orlando Fla. 2011;141(1):121–3.
  • Nishimoto T, Kuwana M. CD4+CD25+Foxp3+ regulatory T cells in the pathophysiology of immune thrombocytopenia. Semin Hematol. 2013;50(Suppl 1):S43–49.
  • Cao J, Li X-Q, Chen C, Zeng L-Y, Cheng H, Li Z-Y, et al. [Imbalance of Th17/Treg cells ratio in peripheral blood of patients with immune thrombocytopenia]. [Zhongguo Shi Yan Xue Ye Xue Za Zhi Zhongguo Bing Li Sheng Li Xue Hui] J Exp Hematol Chin Assoc Pathophysiol. 2011;19(3):730–3.
  • Ji L, Zhan Y, Hua F, Li F, Zou S, Wang W, et al. The ratio of Treg/Th17 cells correlates with the disease activity of primary immune thrombocytopenia. PloS One. 2012;7(12):e50909.
  • Jia R-P, Zhao X-Y. [Expression and clinical significance of CD4(+)CD25(+)Treg cells, sFas and sFasL in peripheral blood of patients with autoimmune thrombocytopenic purpura]. [Zhongguo Shi Yan Xue Ye Xue Za Zhi Zhongguo Bing Li Sheng Li Xue Hui] J Exp Hematol Chin Assoc Pathophysiol. 2011;19(5):1264–7.
  • Aslam R, Hu Y, Gebremeskel S, Segel GB, Speck ER, Guo L, et al. Thymic retention of CD4+CD25+FoxP3+ T regulatory cells is associated with their peripheral deficiency and thrombocytopenia in a murine model of immune thrombocytopenia. Blood 2012;120(10):2127–32.
  • Daridon C, Loddenkemper C, Spieckermann S, Kuhl AA, Salama A, Burmester GR, et al. Splenic proliferative lymphoid nodules distinct from germinal centers are sites of autoantigen stimulation in immune thrombocytopenia. Blood 2012;120(25):5021–31.
  • Mahévas M, Patin P, Huetz F, Descatoire M, Cagnard N, Bole-Feysot C, et al. B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells. J Clin Invest. 2013;123(1):432–42.
  • Dolasik I, Birtas Atesoglu E, Tarkun P, Mehtap O, Keski H, Dogru A, et al. Decreased serum heat shock protein 60 levels in newly diagnosed immune thrombocytopenia patients. Platelets 2015;26(3):220–3.
  • Donato H, Picón A, Martinez M, Rapetti MC, Rosso A, Gomez S, et al. Demographic data, natural history, and prognostic factors of idiopathic thrombocytopenic purpura in children: a multicentered study from Argentina. Pediatr Blood Cancer. 2009;52(4):491–6.
  • Kühne T. Update on the Intercontinental Cooperative ITP Study Group (ICIS) and on the Pediatric and Adult Registry on Chronic ITP (PARC ITP). Pediatr Blood Cancer. 2013;60(Suppl 1):S15–18.
  • Warrier R, Chauhan A. Management of immune thrombocytopenic purpura: an update. Ochsner J. 2012;12(3):221–7.
  • Fogarty PF, Segal JB. The epidemiology of immune thrombocytopenic purpura. Curr Opin Hematol. 2007;14(5):515–9.
  • Newland A, Godeau B, Priego V, Viallard J-F, Lopez Fernandez MF, Orejudos A, et al. A final analysis of a phase 2, single-arm study of platelet (Plt) responses and remission rates in patients with Immune Thrombocytopenia (ITP) receiving romiplostim. Abstract # 2775. Presented at the 56th ASH Annual Meeting, San Francisco, December, 6–9 2014. Available from: https://ash.confex.com/ash/2014/webprogram/Paper67031.html. [Accessed February 5, 2015].
  • Grimaldi D, Canouï-Poitrine F, Croisille L, Lee K, Roudot-Thoraval F, Languille L, et al. Antiplatelet antibodies detected by the MAIPA assay in newly diagnosed immune thrombocytopenia are associated with chronic outcome and higher risk of bleeding. Ann Hematol. 2014;93(2):309–15.
  • Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 2008;371(9610):395–403.
  • Li J, Wang Z, Hu S, Zhao X, Cao L. Correction of abnormal T cell subsets by high-dose dexamethasone in patients with chronic idiopathic thrombocytopenic purpura. Immunol Lett. 2013;154(1–2):42–8.
  • Li J, Wang Z, Dai L, Cao L, Su J, Zhu M, et al. Effects of rapamycin combined with low dose prednisone in patients with chronic immune thrombocytopenia. Clin Dev Immunol. 2013;2013:548085.
  • Li Z, Mou W, Lu G, Cao J, He X, Pan X, et al. Low-dose rituximab combined with short-term glucocorticoids up-regulates Treg cell levels in patients with immune thrombocytopenia. Int J Hematol. 2011;93(1):91–8.
  • Stasi R, Cooper N, Del Poeta G, Stipa E, Laura Evangelista M, Abruzzese E, et al. Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab. Blood 2008;112(4):1147–50.
  • Ling Y, Cao X, Yu Z, Ruan C. Circulating dendritic cells subsets and CD4+Foxp3+ regulatory T cells in adult patients with chronic ITP before and after treatment with high-dose dexamethasome. Eur J Haematol. 2007;79(4):310–6.
  • Clynes R. Immune complexes as therapy for autoimmunity. J Clin Invest. 2005;115(1):25–7.
  • Mahévas M, Fain O, Ebbo M, Roudot-Thoraval F, Limal N, Khellaf M, et al. The temporary use of thrombopoietin-receptor agonists may induce a prolonged remission in adult chronic immune thrombocytopenia. Results of a French observational study. Br J Haematol. 2014;165(6):865–9.
  • Vlachaki E, Papageorgiou V, Klonizakis F, Spandonidou M, Chisan S, Vetsiou E, et al. Total remission of severe immune thrombocytopenia after short term treatment with romiplostim. Hematol Rep. 2011;3(3):e20.
  • Ghadaki B, Nazi I, Kelton JG, Arnold DM. Sustained remissions of immune thrombocytopenia associated with the use of thrombopoietin receptor agonists. Transfusion (Paris) 2013;53(11):2807–12.
  • Bussel JB, Wang X, Lopez A, Eisen M. Case study of remission in adults with immune thrombocytopenia following cessation of treatment with the thrombopoietin mimetic romiplostim. Hematology. 2016;21(4):257–62.
  • José González-López T, Pascual C, Álvarez-Román MT, Fernández-Fuertes F, Sánchez-González B, Caparrós I, et al. Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia. Am J Hematol. 2015;90(3):E40–3.
  • Bao W, Bussel JB, Heck S, He W, Karpoff M, Boulad N, et al. Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents. Blood 2010;116(22):4639–45.
  • May AE, Kälsch T, Massberg S, Herouy Y, Schmidt R, Gawaz M. Engagement of glycoprotein IIb/IIIa (alpha(IIb)beta3) on platelets upregulates CD40L and triggers CD40L-dependent matrix degradation by endothelial cells. Circulation 2002;106(16):2111–7.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.