ITPTTP诊治新进展.ppt

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分组切脾率治疗失败率严重不良事件率治疗相关严重不良事件率Romiplostim标准治疗组9% (14/157)36%（28/77）12%(18/157) 30%（23/77）23%37%5%8%p6月、对一种或以上标准治疗无效、plt50 x 109/L)o结果：62%起效(CR+PR+MR), 29%获得CRo结论：低剂量结论：低剂量veltuzumab (2次次, 间隔间隔2w) 在复发性在复发性ITP疗效可，疗效可， 与静脉注射相比，皮下注射更方便与静脉注射相比，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 Primary Immune Thrombocytopenia o长期随访发现，与长期随访发现，与Dex单药组相比，单药组相比， Dex联合联合Rituximab组在长期不良反应、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治疗等方面无显著性差异分组复发率30月RD率需特异性抗ITP治疗率Dex单药组Dex联合Rituximab组Dex+Rituximab抢救治疗组23%(3/13)23%(6/26)14%(2/14)77% 71%85% 33%29%36%Francesco Zaja et al. Poster Session: Disorders of Platelet Number or Function poster 2415.High-Dose IgG Alters the Relative Expression of Fcgamma RIIA and Fcgamma RIIB On Human Macrophages: A Mechanism for IVIG Therapy in Human Immune Thrombocytopeniao影响巨噬细胞影响巨噬细胞FcgammaRIIA/FcgammaRIIB平衡可能是平衡可能是 IVIG 在在ITP治疗中的机制之一治疗中的机制之一Relative Efficacy of Steroid Therapy in Ameliorating Autoimmune Thrombocytopenia Mediated by Anti-Platelet GPIIbIIIa Versus GPIbAntibodiesn 与与GPIIbIIIa相比，相比，GPIb抗体介导的抗体介导的ITP患者对患者对IVIG和激素治疗疗效和激素治疗疗效 差差Salley Pels, 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 treatments o羟氯喹对抗核抗体阳性且对一线治疗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主要包括糖皮质激素)不能取得不能取得长期疗效的长期疗效的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诊断标准的诊断标准的ITP患者患者Time to Splenectomy Failure in Patients with Recurrent or Refractory Chronic Immune Thrombocytopenic Purpura n 脾切除脾切除1年内有效率年内有效率51%，5年后年后27%，10年后降到年后降到18%，随时间延长，随时间延长 有效率降低有效率降低Amelie Charbrol, et al. Poster Session: Disorders of Platelet Number 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 o 淋巴细胞淋巴细胞FAS途径的异常可能在部分途径的异常可能在部分ITP的发病中起到作用的发病中起到作用Impaired Interaction Between Regulatory T Cells and Dendritic Cells in Immune Thrombocytopenia n ITP患者中患者中CD4+CD25+Treg 抑制抑制DCs细胞成熟的能力降低，细胞成熟的能力降低，Treg 和和DCs之间作用异常可能参与之间作用异常可能参与ITP的发病的发病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 IgA Immunoglobulin Level and Response to Treatment for Immune Thrombocytopenia (ITP) o血浆血浆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机制需要进一步研究 Plasma Cytokines Associated with Low Platelet Counts in Aplastic Anemia and Immune Thrombocytopenian ITP患者血浆患者血浆CCL5、CD40L、CXCL5、EGF等均下降，且等均下降，且plt和巨和巨 核细胞表达上述基因核细胞表达上述基因Jon E. Arnason, et al. Poster 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诊治新进展诊治新进展HLA-DRB1*11: a Strong Risk Factor for Acquired Severe ADAMTS13 Deficiency-Related Idiopathic Thrombotic Thrombocytopenic Purpura in CaucasiansPaul Coppo, et al. Poster Session: Pathophysiology of Thrombosis Post 2412o研究提示白种人中DRB1*11是获得性特发性TTP的高危因素，o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 Subcutaneous Administrations to Healthy VolunteersKhalid 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 1063First-Line Rituximab Efficacy and Safety in Patients with Acquired 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 MicroangiopathiesAntoine Froissart目的-对TPE常规治疗不佳的aiTTP，美罗华的有效性和安全性。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。 R+ R-1人死亡，21人坚持治疗试验前5人死亡，52人坚持治疗中位PLT恢复时间20天（14-33天）第一次美罗华治疗到PLT恢复中位时间10天（5-27天）与R+组无统计学差异中位血浆置换量950ml/kg（310-1940ml/kg）与R+组无统计学差异ADAMTS13及抗体 ADAMTS13R-组 在12月时差别消失复发一年内无复发，3个病人在21.2 13.8月复发Antoine Froissart, et al. Poster Session: Pathophysiology of Thrombosis Post 890Thienopyridine-Associated Thrombotic Thrombocytopenia Purpura: Updated Antibody Results From the SERF-TTP StudyAnaadriana 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. 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。 严重血小板减少 噻氯匹定 氯吡格雷 90% 13% 严重ADAMTS13缺陷80% 0 抗ADAMTS13抗体100% 0少于两周用药 050%治疗性血浆置换 85% 50%复发2例复发，与特发性TTP同Anaadriana Zakarija, et al. Poster Session: Pathophysiology of Thrombosis Post 892Part III: DIC，VIII因子缺乏性疾病新进因子缺乏性疾病新进展展DIC患者中抗肝素血小板因子4抗体(AHPF4)的阳性率o用GTI和Hyphen Biomedical两种方法检测25例可疑DIC患者血浆中AHPF4的表达o25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。 oDIC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: Disorders of Coagulation or Fibrinolysis Poster I 2094Non Overt DIC 诊断标准评价o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%)onon-overt DIC 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o36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o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 Christine L Kempton, et al.Post session: Disorders of Coagulation or Fibrinolysis Poster I 3184The Relative Health-Related Quality of Life Burden of Severe Hemophilia A and the Impact of Target Joint Developmeno1.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的影响o141例成年患者o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: 2000-2008o评价美国医院非适应症使用rFVIIa 情况2000.1.12008.12.31o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 Nationwide Study in Brazil （巴西全国范围内血友病患者冠心病患病率的调查）o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。o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。o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。o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 1404Part IV:血栓、抗凝治疗新进展血栓、抗凝治疗新进展Cohn DM, et al. Poster Session: Pathophysiology of Thrombosis Post 2973o737 women were included, 220 with proven APS;o(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）;o(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 Antiphospholipid Syndrome: Prognosis and Predictors of a Subsequent Successful DeliveryProcoagulants and Subclinical Atherosclerosis in Young Adults: The CARDIA Study o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；oAssays of FVII, FVIII, and vWF were performed in 1255 participants ages 23-37 and repeated at ages 38-50;oFVII 可作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 2973Risk Stratification of Recurrent Venous Thromboembolism oRetrospective study covering more than 20 years after a first venous thromboembolic event in a group of 1,440 patients with VTE;o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;o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 2981Extended Follow-up of the Prospective Cohort Study That Derived the “Men Continue 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)o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;o646 participants, a mean 3.1 years of follow-up, 131/512 suspected VTE were adjudicated as recurrent VTE; o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 451Risk Assessment Model to Predict Recurrence in Patients with Unprovoked Deep Vein Thrombosis or Pulmonary Embolism o建立可预测无诱因VTE患者复发风险度的模型;o929 patients with a first VTE after completion of at least 3 months of anticoagulation;o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；o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 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 Coagulationo27例复发CLL患者，来那度胺20mg、10mg进行治疗 ;oTNF-, soluble vascular endothelial adhesion molecule 1 (sVCAM), C-reactive protein, D-dimer and soluble thrombomodulin were examined;o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, et al. Oral Session: Pathophysiology of Thrombosis: Risk of Venous Thrombosis 455.Cisplatin-Based Chemotherapy Is Associated with An Unacceptably High Incidence of Thromboembolic Events: A Large Retrospective Analysiso评估顺铂为基础的化疗患者血栓栓塞事件发生率;o936 patients received at least one dose of cisplatin；o接受顺铂化疗肿瘤患者中，血栓栓塞事件发生率为18.3%，其中部分都发生于化疗后3个月内；o推荐对顺铂化疗患者进行抗血栓治疗； Russell A.M, et al. Oral Session: Pathophysiology of Thrombosis: Risk of Venous Thrombosis 456.High Incidence of Arterial Thrombosis in Young Patients Treated for Multiple Myeloma:Results of a Prospective Cohort Studyo评价年龄66 岁既往未治疗MM患者ATE发生风险因素；o195 patients were treated according to the HOVON 50 study protocol (VADTADPAD, bortezomib);oMM 患者化疗后ATE发生率增高， fVIII水平, 增高与ATE发生风险增加相关。Eduard JL, et al. Oral Session: Pathophysiology of Thrombosis 149. A Phase III Study of Enoxaparin vs Aspirin vs Low-Dose Warfarin as Thromboprophylaxis for Newly Diagnosed Myeloma Patients Treated with Thalidomide Based-Regimenso评价Enoxaparin、低剂量阿司匹林、低剂量华法林作为MM患者抗凝预防治疗的安全性和有效性；o991例MM 患者随机接受 VTD 、TD 、VMPT、VMP化疗 ，并应用上述抗凝剂进行抗凝治疗;oPatients treated with VTD or TD or VMPT were randomly assigned to receive LMWH (Enoxaparin 40 mg/d, N=223) or ASA (Aspirin 100 mg/d, N=227) or WAR (Warfarin 1.25 mg/d, N=223);EventsLMWH(N = 217)ASA(N = 225)WAR(N = 219)VMP(N = 238)Grade 3-4 thrombotic events, (%)5682Acute cardiovascular events, (%)210.51Sudden deaths, (%)0000Major and minor bleeding, (%)2314Total events, (%)91097Incidence of thrombotic events, acute cardiovascular events, sudden death and bleeding events Palumbo A, et al. Oral Session: Antithrombotic Therapy in Special Populations 492.