ITP、TTP诊治新进展.ppt

1、Part I: ITP诊治新进展,Comparison of Splenectomy and Treatment Failure Incidence in Nonsplenectomized Patients with Immune Thrombocytopenia (ITP) Receiving Romiplostim or Medical Standard of Care: 1-Year Treatment and 6-Month Safety Follow-up,Romiplostim 显著降低未切脾ITP患者切脾率和治疗失败率，安全性 与标准治疗组相似,David J Kuter, e

2、t al. Oral Session: Disorders of Platelet Number or Function 679.,Long-Term Efficacy and Safety of Romiplostim for the Treatment of Patients with Chronic Immune Thrombocytopenia (ITP): 5-Year Update From an Open-Label Extension Study,最常见不良事件：头痛(32%)、鼻咽炎(30%)、挫伤(28%)、疲惫(28%) 等; 17例发生血栓( 6% )，随随访时间延长发

3、生率并未增加；9例骨髓网状蛋白增多，但未发展为纤维化；2例出现中和性抗体，停药后消失; 结论：5年随访发现，应用Romiplostim长期治疗ITP能够维持plt数目，剂量调节方便，耐受性好，不良事件发生率并未随时间延长而增加;,James B. Bussel, et al. Oral Session: Disorders of Platelet Number or Function 681.,Evaluation of Bleeding-Related Episodes in Patients with Chronic Immune Thrombocytopenia (ITP) Treate

4、d with Romiplostim in Two Phase 3 Placebo-Controlled Clinical Trials,Romiplostim明显降低BREs发生率，减少丙球使用率，在切脾 及未切脾两组效果相似,Antoine Froissart et al. Poster Session: Disorders of Platelet Number or Function poster 891.,Evaluation of Bleeding-Related Episodes in Patients with Chronic Immune Thrombocytopenic Pu

5、rpura (ITP) Receiving Romiplostim or Medical Standard of Care,对象：成人未切脾ITP患者， Romiplostim组154例，SOC组70例，治疗52w 结果：与SOC组相比，Romiplostim组患者BREs发生率下降67%（3.1% vs 9.4%)，应用免疫球蛋白率下降95%（0.2% vs 4.8%） 结论：与SOC相比，Romiplostim能够显著降低BREs发生率及应用免疫球蛋白率,Roberto Stasi, et al. Poster Session: Disorders of Platelet Number o

6、r Function poster 1311.,Long-Term Treatment of Chronic Immune Thrombocytopenic Purpurawith Oral Eltrombopag: Results From the EXTEND Study,对象：299例患者，起始剂量50mg/d,调整剂量(25-75mg/d)， 使plt在50-200 x109/L 结果：86%患者plt50 x 109/L，切脾和未切脾患者效果相似(89%和82%) 不良反应：83%出现轻到中度不良反应，最常见的是头痛(23%)、上呼吸道感染(17%)、鼻咽炎(17%)、疲乏(13%)

7、、关节痛(12%)、腹泻(11%)等。此外肝功改变(8%)、血栓(4%)。86例骨髓活检(开始治疗1年后)中未发现治疗相关改变。 结论：2年随访发现，口服Eltrombopag耐受性好，能够有效提升plt数目、减少出血症状,Mansoor N. Saleh el al. Oral Session: Disorders of Platelet Number or Function 682.,Thromboembolic Events Observed in Eltrombopag Clinical Trials in Chronic Immune Thrombocytopenic Purpura

8、,TRA100773A, TRA100773B, RAISE， REPEAT和EXTEND 治疗前TEEs(血栓事件)发生率为3.2%(16/493), 治疗后Eltrombopag组发生率为3.8%(17/446),而安慰剂组无TEEs发生 最常见的TEEs是深静脉血栓(n=8)和肺动脉血栓(n=6)82%(14/17)的TEEs发生在低于最高plt值， 18%(3/17)发生在接近最高plt值时 结论：TEEs发生于Eltrombopag组，与治疗前无显著性差异，TEEs与plt不存在相关,James B. et al . Poster Session: Disorders of Plat

9、elet Number or Function poster 2433.,Results of Bone Marrow Examinations in Patients with Chronic Immune Thrombocytopenic Purpura Treated with Eltrombopag,RAISE, REPEAT和EXTEND 应用Eltrombopag18个月并未出现临床相关骨髓异常或骨髓纤维化,Platelet Counts Following Eltrombopag Discontinuation in Patients with Chronic Immune Th

10、rombocytopenic Purpura,TRA100773A，TRA100773B和RAISE 停用Eltrombopag后血小板减低和安慰剂组相似，plt 短暂 降低可能与停用ltrombopag无关，而是反映ITP患者plt波动，且plt 降低与出血无关,Xingmin Feng, et al. Poster Session: Disorders of Platelet Number or Function poster 3517.,James B. et al . Poster Session: Disorders of Platelet Number or Function po

11、ster 2435.,Improved Regulatory T Cell Activity in Patients with Chronic Immune Thrombocytopenia Purpura Treated with Thrombopoietic Agents,对象：治疗前组6例，促血小板生成物治疗组12例(Nplate n=5， eltrombopag n=2，AKR-501 n=5)，对照组15例 结果：治疗前后Treg数目无显著变化，但是用药后Treg抑制功能 明显改善并伴随细胞群(如分泌IL-2的Th细胞降低，Th1细胞降低) 和细胞因子表达的改变(如sCD40L下降和

12、TGF-b上升) 结论：促血小板生成物能够改善 ITP患者Treg功能,Weili Bao et al. Oral Session: Disorders of Platelet Number or Function poster 684.,Subcutaneous Injections of Low-Dose Anti-CD20 Veltuzumab for Treatment of Relapsed Immune Thrombocytopenia (ITP),多中心、I/II期临床试验 对象：25例ITP患者（病史6月、对一种或以上标准治疗无效、plt50 x 109/L) 结果：62%起效

13、(CR+PR+MR), 29%获得CR 结论：低剂量veltuzumab (2次, 间隔2w) 在复发性ITP疗效可， 与静脉注射相比，皮下注射更方便,Mansoor N. Saleh el al. Poster Session: Disorders of Platelet Number or Function poster 1322.,Long Term Follow up Analysis Following Front Line Therapy with Dexamethasone or Dexamethasone Plus Rituximab in Adults with Primar

14、y Immune Thrombocytopenia,长期随访发现，与Dex单药组相比， Dex联合Rituximab组在长期不良反应、复发率、有效时间和所需进一步特异性抗ITP治疗等方面无显著性差异,Francesco Zaja et al. Poster Session: Disorders of Platelet Number or Function poster 2415.,High-Dose IgG Alters the Relative Expression of Fcgamma RIIAand Fcgamma RIIB On Human Macrophages: A Mechani

15、sm for IVIG Therapy in Human Immune Thrombocytopenia,影响巨噬细胞FcgammaRIIA/FcgammaRIIB平衡可能是 IVIG 在ITP治疗中的机制之一,Relative Efficacy of Steroid Therapy in Ameliorating Autoimmune Thrombocytopenia Mediated by Anti-Platelet GPIIbIIIa Versus GPIbAntibodies,与GPIIbIIIa相比，GPIb抗体介导的ITP患者对IVIG和激素治疗疗效 差,Salley Pels,

16、et al. Oral Session: Disorders of Platelet Number or Function poster 683.,Lili Tao et al. Poster Session: Disorders of Platelet Number or Function poster 1323.,Hydroxychloroquine for the Treatment of Immune Thrombocytopenia Associated with Antinuclear Antibody in Patients Refractory to First- Line t

17、reatments,羟氯喹对抗核抗体阳性且对一线治疗(主要包括糖皮质激素)不能取得长期疗效的ITP患者是一种安全、有效的药物，尤其是同时符合SLE诊断标准的ITP患者,Time to Splenectomy Failure in Patients with Recurrent or Refractory Chronic Immune Thrombocytopenic Purpura,脾切除1年内有效率51%，5年后27%，10年后降到18%，随时间延长 有效率降低,Amelie Charbrol, et al. Poster Session: Disorders of Platelet Num

18、ber or Function poster 2414.,Gregory Cheng， et al. Poster Session: Disorders of Platelet Number or Function poster 3522.,Lymphocyte Homeostasis FAS Pathway Is Altered in Some Patients with Immune Thrombocytopenia,淋巴细胞FAS途径的异常可能在部分ITP的发病中起到作用,Impaired Interaction Between Regulatory T Cells and Dendri

19、tic Cells in Immune Thrombocytopenia,ITP患者中CD4+CD25+Treg 抑制DCs细胞成熟的能力降低，Treg 和DCs之间作用异常可能参与ITP的发病,Nichola Cooper, et al. Poster Session: Disorders of Platelet Number or Function poster 3514.,Lucia Catani et al. Poster Session: Disorders of Platelet Number or Function poster 3511.,Association Between

20、 IgA Immunoglobulin Level and Response to Treatment for Immune Thrombocytopenia (ITP),血浆IgA水平高的患者对标准治疗效果差，但对脾切除效果好，具体机制需要进一步研究,Plasma Cytokines Associated with Low Platelet Counts in Aplastic Anemia and Immune Thrombocytopenia,ITP患者血浆CCL5、CD40L、CXCL5、EGF等均下降，且plt和巨 核细胞表达上述基因,Jon E. Arnason, et al. P

21、oster Session: Disorders of Platelet Number or Function poster 3503.,Xingmin Feng et al. Poster Session: Disorders of Platelet Number or Function poster 1317.,Part II: TTP诊治新进展,HLA-DRB1*11: a Strong Risk Factor for Acquired Severe ADAMTS13 Deficiency-Related Idiopathic Thrombotic Thrombocytopenic Pu

22、rpura in Caucasians,Paul Coppo, et al. Poster Session: Pathophysiology of Thrombosis Post 2412,研究提示白种人中DRB1*11是获得性特发性TTP的高危因素， 同时提示作为有特定基因危险因素的TMA中的获得性特发性TTP，应将它从其他的特发性TMA中区别出来。,Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Anti-Vwf Nanobody ALX-0681 After Single and Multiple Subcut

23、aneous Administrations to Healthy Volunteers,Khalid Abd-Elaziz 目的-验证ALX-0681用药的最大耐受剂量，有效剂量进一步设计二期试验。 方法- 36人试验 安慰剂随机对照 结论-ALX-0681是安全的，耐受性良好，且没有免疫原性反应。,Khalid Abd-Elaziz, et al. Poster Session: Pathophysiology of Thrombosis Post 1063,First-Line Rituximab Efficacy and Safety in Patients with Acquired

24、 Idiopathic Thrombotic Thrombocytopenic Purpura Experiencing a Non Optimal Response to Therapeutical Plasma Exchange: Results of a Prospective Multicenter Phase 2 Study From the French Reference Center for the Management of Thrombotic Microangiopathies,Antoine Froissart 目的-对TPE常规治疗不佳的aiTTP，美罗华的有效性和安

25、全性。 方法-前瞻性多中心的开放式二期临床试验 R+组-22人-d1，4，8，15四次美罗华，同时TPE治疗，每次美罗华治疗前和此后第3，6，9，12月测外周B细胞数。 R-组-57人-36人-常规TPE -21人-加用长春新碱 两组均在3，6，9，12月测ADAMTS13活性。,Antoine Froissart, et al. Poster Session: Pathophysiology of Thrombosis Post 890,结论-美罗华可通过提高ADAMTS13活性缩短aiTTP的治疗时间，防止一年内复 发，但不能预防长期复发。是否引入美罗华作为规范治疗，还需继续研究。,Ant

26、oine Froissart, et al. Poster Session: Pathophysiology of Thrombosis Post 890,Thienopyridine-Associated Thrombotic Thrombocytopenia Purpura: Updated Antibody Results From the SERF-TTP Study,Anaadriana Zakarija 目的-分析吡啶 相关性TTP的两种机制。 方法-噻氯匹定相关性TTP-30例 氯吡格雷相关性TTP-10例 特发性TTP-5例,Anaadriana Zakarija, et al

27、. Poster Session: Pathophysiology of Thrombosis Post 892,结论-噻氯匹定-TTP提示通过抗ADAMTS13途经作用，且呈药物依赖性。氯吡格雷 TTP非以来ADAMTS13途径。,Anaadriana Zakarija, et al. Poster Session: Pathophysiology of Thrombosis Post 892,Part III: DIC，VIII因子缺乏性疾病新进展,DIC患者中抗肝素血小板因子4抗体(AHPF4)的阳性率,用GTI和Hyphen Biomedical两种方法检测25例可疑DIC患者血浆中A

28、HPF4的表达 25例中，GTI方法检测到24例AHPF4阳性，而Hyphen Biomedical法有16例阳性，只有9例是两种方法检测都是阳性。GTI/Hyphen Biomedical法检测阳性的标本对14C血清素均不起反应。进一步的研究发现这些患者中只有8例之前接触过肝素，只有4例检测到含有低水平的肝素。且这些标本中存在血小板活化产物例如PF4,选择素，P-选择素。 DIC中，由于血小板消耗导致血小板减少，但AHPF4对血小板减少不起任何作用，循环中PF4及其他细胞因子的升高可能导致DIC患者体内AHPF4抗体的产生。,Jawed Fareed ,et al. Post session

29、: Disorders of Coagulation or Fibrinolysis Poster I 2094,Non Overt DIC 诊断标准评价,共613例： overt-DIC 29.5% 多为产科疾病或者合并肝病 Pre-DIC state 7.2% 其中12.2%合并血液科肿瘤 non-overt DIC 发展为overt-DIC 97.8 % 合并Pre-DIC state 97.7 % 不变为overt-DIC 17.0% 28天致死率overt DIC (37.6%)，non-overt DIC (32.9%)，pre-DIC (27.3%) non-overt DIC

30、诊断标准应更敏感，它不仅能诊断DIC，而且能够预测DIC的早期阶段,Hideo Wada, et al. Post session: Disorders of Coagulation or Fibrinolysis Poster I 1297,轻中度A型血友病产生抑制物的危险因素： 一项病例对照研究,36例轻中度患者（抑制物滴度1 BU/ml） 62例对照（抑制物滴度0.6 BU/ml或之前用VIII因子治疗过） 接受VIII因子强力治疗六天或以上，12周内检测抑制物生成情况 在轻中度A型血友病患者中，VIII因子强力治疗是导致产生抑制物的一个不稳定的危险因素，且在年龄30岁者危险程度更高,C

31、hristine L Kempton, et al. Post session: Disorders of Coagulation or Fibrinolysis Poster I 3184,The Relative Health-Related Quality of Life Burden of Severe Hemophilia A and the Impact of Target Joint Developmen,1.比较严重血友病A患者相对于健康人样本、总人口样本及其他慢性病患者（慢性背痛、类风湿关节炎、癌症）的健康相关生活质量(HRQOL)负担 2.存在至少一个靶关节对HRQOL的影

32、响 141例成年患者 严重血友病患者生活质量明显降低 身体负担类似于类风湿及癌症患者 防止靶关节的出现可以显著提高其生活质量 与其他三种慢性病相比，血友病患者的心理相关生活质量较高,Joshua D Epstein, et al. Post session: Disorders of Coagulation or Fibrinolysis Poster I 1404.,Off-Label Use of Recombinant Factor VIIa in United States Hospitals: 2000-2008,评价美国医院非适应症使用rFVIIa 情况2000.1.12008.1

33、2.31 住院病人非适应症使用rFVIIa 远远超过适应症患者2008年心脏外科手术、外伤和非外伤性颅内出血使用率最高，占18,311 其中的12,448 (68%) suggesting a substantial proportion of end-stage use of rFVIIa,Aaron C. Logan, et al. Oral session: Disorders of Coagulation or Fibrinolysis 67.,Prevalence of Coronary Heart Disease in Patients with Hemophilia: a Nat

34、ionwide Study in Brazil （巴西全国范围内血友病患者冠心病患病率的调查）,对全国范围内超过5000 例病人的调查发现血友病患者中合并CAD的发生率很低。 由于小样本的原因，目前没有可以收集的关于危险因素的信息。 在增加凝血因子活性，确保病人安全的情况下可实施外科手术。 尽管在理论上会有增加出血的危险，但是用抗血小板药物治疗合并CAD的血友病患者是有必要的。,Claudia Bley, et al, Post session: Disorders of Coagulation or Fibrinolysis Poster I 1404,Part IV:血栓、抗凝治疗新进展,

35、Cohn DM, et al. Poster Session: Pathophysiology of Thrombosis Post 2973,737 women were included, 220 with proven APS; (1) APS习惯性流产妇女与原因未明的习惯性流产妇女成功妊娠率无显著差异（67% vs 63%，P 0.05）; (2) 肝素和阿司匹林合用可以显著提高APS患者成功妊娠几率（79% vs 59%），但对APS习惯性流产患者成功妊娠率无显著影响；,Recurrent Miscarriage in Women with and without Antiphosp

36、holipid Syndrome: Prognosis and Predictors of a Subsequent Successful Delivery,Procoagulants and Subclinical Atherosclerosis in Young Adults: The CARDIA Study,研究年轻亚临床动脉粥样硬化患者与其凝血因子与的关联性； Assays of FVII, FVIII, and vWF were performed in 1255 participants ages 23-37 and repeated at ages 38-50; FVII 可作

37、为年轻亚临床动脉粥样硬化发生率增高的标记物，但不是一个独立危险因素; FVIII 与年轻亚临床动脉粥样硬化患者动脉内膜厚度呈正相关, 未发现vWF与动脉粥样硬化存在相关性；,Green D, et al. Poster Session: Pathophysiology of Thrombosis Post 2973,Risk Stratification of Recurrent Venous Thromboembolism,Retrospective study covering more than 20 years after a first venous thromboembolic e

38、vent in a group of 1,440 patients with VTE; 首次特发性VTE患者年复发率为5%，若存在易栓症相关危险因素，VTE危险性加倍，这提示特发性VTE患者首发VTE后需要长期口服抗凝治疗; 除现行 ACCP 推荐指南VTE危险因素外, 易栓危险因素更具临床相关性；,Zotz RB, et al. Poster Session: Pathophysiology of Thrombosis Poster 2981,Extended Follow-up of the Prospective Cohort Study That Derived the “Men Co

39、ntinue and HERDOO2” Clinical Decision Rule Which Identifies Low Risk Patients Who May Be Able to Discontinue Oral Anticoagulants (Oac) 5-7 Months After Treatment for Unprovoked (VTE),鉴定低危险度无诱因VTE患者中可在5-7月口服抗凝治疗后停药者; 646 participants, a mean 3.1 years of follow-up, 131/512 suspected VTE were adjudica

40、ted as recurrent VTE; 男性和高血栓危险度女性无诱因VTE患者3年随访VTE复发几率增加，应考虑长期口服抗凝剂治疗。女性低HERDOO2得分患者可考虑5-7月后停止口服抗凝治疗；,Michael J. K, et al. Oral Session: Pathophysiology of Thrombosis: Risk of Venous Thrombosis 451,Risk Assessment Model to Predict Recurrence in Patients with Unprovoked Deep Vein Thrombosis or Pulmonar

41、y Embolism,建立可预测无诱因VTE患者复发风险度的模型; 929 patients with a first VTE after completion of at least 3 months of anticoagulation; 通过运用一套简单的评分系统，VTE复发风险评估准确率显著改善； 可缩短抗凝治疗时间的低复发风险的无诱因VTE患者可以被该评分系统判定出；,Nomogram for predicting recurrence risk. For each value of sex, location and D-D, read off points at the very

42、 top of the nomogram.,Sabine E, et al. Oral Session: Pathophysiology of Thrombosis: Risk of Venous Thrombosis 452.,Increased Incidence of Thrombosis with Lenalidomide in Chronic Lymphocytic Leukemia: Effect of Lenalidomide On Inflammation, Endothelial Cell Damage and Coagulation,27例复发CLL患者，来那度胺20mg、10mg进行治疗 ; TNF-, soluble vascular endothelial adhesion molecule 1 (sVCAM), C-reactive protein, D-dimer and soluble thrombomodulin were examined; 来那度胺所致炎症综合征患者中DVT发生率为19%，TNF释放与内皮损伤呈正相关，来那度胺应用第一周期时TNF 较高患者，DVT发生率显著增高，可考虑应用抗炎治疗、TNF拮抗剂治疗。,Sabine E,