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Nomenclature
Idiopathic Thrombocytopenic Purpura (ITP)
Immune Thrombocytopenia (ITP)
2007
International ITP working group. Blood. 2009, 113(11):2386-93.
Phases of ITP
International ITP working group. Blood. 2009, 113(11):2386-93.
0 6 Months
Chronic ITPAcute ITP
2007
0 3 Months 12 Months
Newly ITP Persistent ITP Chronic ITP
Pathogenesis of ITP
Decreased productionIncreased destruction
Humoral immunity Cell immunity
SpleenRES
Liver Desialya
tion
CTLlysis
Liver Desialya
tion
J Immunol. 2015 Jun 15;194(12):5579-5587.Br J Haematol. 2014 Apr;165(2):248-58
Loss of Immune tolerance
Dysmegakaryocytopoiesis
Differentiation
Aapoptosis
Desialyation
Hepatocytes
PLT PLT
Platelet desialylation
Qiu J, ASH Annual Meeting Abstracts, 2014Ni H, Nat Communication, 2015
Laboratory Diagnosis of ITP
Curr Hematol Rep. 2005 Mar;4(2):160-5. Br J Haematol. 2009 Sep;146(6):585-96. Eur J Haematol. 2011 Apr;86(4):339-46. Br J Haematol. 1998 Jun;101(3):420-4.
• Treatment not indicated
• platelet > 30×109/L
• no bleeding symptom
• no increased risk of bleeding
International ITP working group. Blood. 2009, 113(11):2386-93.
ITP therapy
• Conventional PDN
• HD-DXM
International ITP working group. Blood. 2009, 113(11):2386-93.
First-line treatment
short-term application
Conventional PDN vs HD-DXM
• One or two courses of HD-DXM demonstrated higher CR rate,
shorter time to response and less adverse events than PDN.
Wei Y, et al, Conventional Oral Prednisone Versus High-Dose Dexamethasone for Management of Adult Immune Thrombocytopenia: A Prospective Randomized Multicenter Clinical Trial, 2014 ASH abstract, 1455
NCT01356511
N Engl J Med. 2007; 357(22):2237-47. Lancet. 2008;371(9610):395-403.Lancet. 2009;373(9664):641-8. N Engl J Med. 2010;363(20):1889-99.Int J Hematol. 2012;96(2):222-8. Blood. 2015;125(10):1541-7.
Second-line treatment - 1
• Rituximab
• long TTR
• high sustained response rate
Blood. 2001;98(4):952-7. Ann Intern Med. 2007;146(1):25-33.Haematologica. 2008; 93(6):930-3. Blood. 2012;119(25):5989-95.Blood. 2015;125(10):1541-7. Lancet. 2015;385(9978):1653-61.
Second-line treatment - 2
• Splenectomy
• 32% sustained response
• surgical risk
• post-splenectomy state
Blood. 2004;104(9):2623-34. Blood. 2013;121(23):4782-90.
Second-line treatment - 3
• DXM plus Rituximab
• DXM plus Eltrombopag
• rhTPO plus Rituximab
• DXM, Rituximab and Cyclosporin
Blood. 2015;125(10):1541-7.
Blood. 2010;115(14):2755-62.
David GA. ASH Annual Meeting Abstracts, 2013
Blood. 2015 May 13. Epub ahead of print
Combined therapy
Definition of response
• CR: platelet count > 100×109/L and absence of bleeding
• R: platelet count > 30×109/L and at least 2-fold increase the baseline
count and absence of bleeding
• NR: platelet count < 30×109/L or less than 2-fold increase of baseline
ITP: The Next Decade
• Restoration of immune tolerance
• Tregs/Bregs
• BAFF/BAFF-R antagonist
• MSC/Thalidomide
• MDSC
• DANA/Oseltamivir
• Anti-inflammatory macrophages/dasatinib