DisseminatedIntravascularCoagulationPPT课件.ppt
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1、1,Dengli Hong MD PhD Group head of medical stem cell biology Shanghai Jiao-Tong University School of Medicine Key Lab of Cell Differentiation and Apoptosis of Chinese Ministry of Education,TEL: 021-64666992 EMAIL: http:/ 研究员 医学干细胞研究组组长,贡献:致力于研究干细胞疾病中干细胞在生理和病理性niche中的功能和基因组稳定性及克隆性演化。成果发表在Science、 Ce
2、ll Stem Cell和 JCI等杂志。 最重要的贡献是,第一次鉴定了前白血病干细胞(Hong D, et al. Science 2008),被认为是肿瘤研究的重大突破,延伸研究提出了肿瘤干细胞的克隆性演化模型。,教育经历: 1992,武汉同济医科大学临床医学本科。 1998,武汉同济医科大学血液内科研究生。 2009,牛津大学分子医学研究所哲学博士。 工作简历: 1998-2000武汉 同济医科大学附属同济医院血液内科医师。 2000-2003 意大利都灵大学IRCC肿瘤研究所博士后。 2003-2006 英国牛津大学WIMM分子医学研究所助理研究员。 2006-2009 英国牛津大学W
3、IMM分子医学研究所研究员。 2009-今 上海交大医学科学研究院/细胞分化与凋亡教育部重点实验室研究员, 医学干细胞组组长。,医学干细胞研究组欢迎你!,研究方向: 1.干细胞在肿瘤起始和发展过程中的克隆性演化和表观遗传调控。 2.造血干细胞在生理和病理性niche中的功能和基因组稳定性。 3. 重编程干细胞在医学上的应用。,正在承担的研究项目: 国家自然基金重大研究计划培育项目:TEL-AML1启动的干细胞克隆性演化的表观遗传调控机制。(2010-2012) 2国家自然科学基金重大国际合作研究项目:BCR-ABL 相关急性淋巴细胞白血病干细胞的克隆性演化的遗传变异多样性。(2012-2016
4、) 3973子项目:肿瘤干细胞的动态演进及干预研究。(2012-2016),掌握和熟悉内容,1. Definition of DIC 2. Causes of DIC 3. Pathogenesis of DIC 4. Predisposing factors to DIC 5. Main clinical features of DIC 6. Types and stages of DIC 7. Treatment of DIC,Definition,Disseminated intravascular coagulation (DIC) is a complex systemic thro
5、mbohemorrhagic disorder involving the generation of intravascular fibrin, the consumption of procoagulants and platelets, and secondary activation of fibrinolysis. The resultant clinical condition is characterized by intravascular coagulation and hemorrhage.,掌握和熟悉内容,1. Definition of DIC 2. Causes of
6、 DIC 3. Pathogenesis of DIC 4. Predisposing factors to DIC 5. Main clinical features of DIC 6. Types and stages of DIC 7. Treatment of DIC,Diseases associated with DIC,Sepsis/severe infection 30% Malignancy 25% solid and myeloproliferative malignancies Obstetric complications 20% Amniotic fluid embo
7、lism, Abruptio placentae Retained dead fetus syndrome Trauma (neurotrauma) ,Organ destruction, Burns 15% Severe hepatic failure Rheumatologic illness Adult Stills disease, Lupus Vascular abnormalities Kasabach-Merritt syndrome, Large vascular aneurysms Hemolysis,Triggering factors, Release TF VEC in
8、jury LPS Ag-Ab complex, Protease Microparticles Pathogenic Microbes (viruses),掌握和熟悉内容,1. Definition of DIC 2. Causes of DIC 3. Pathogenesis of DIC 4. Predisposing factors to DIC 5. Main clinical features of DIC 6. Types and stages of DIC 7. Treatment of DIC,Balance between coagulation and anti-coagu
9、lation,血管痉挛,血小板血栓形成,纤维蛋白凝块形成,止血的过程,stop,remove,Coagulation cascade,Fribrin,Fibrinogen,FM,VIII,VIIIa,Ca2+,Intrinsic pathway,Extrinsic pathway,Coagulation cascade,Fribrin,Fibrinogen,FM,VIII,VIIIa,Ca2+,Intrinsic pathway,Extrinsic pathway,Anti-coagulation,Cellular system: Monocyte/ Macrophage Anticoagul
10、ants in plasma AT,TFPI,heparin co-factor II 可灭活a,a,a,a,a等; 凝血酶与血管内皮细胞表面肝素样物质结合,继而被AT- 灭活 Protein C system,Protein C system,蛋白C,激活的蛋白C(APC),灭活a,a,内皮细胞,血栓调节蛋白TM,Fibrinolytic system,降解纤维蛋白,水解凝血酶、凝血因子,内源性凝血时,PK分解产生激肽释放酶 外源性凝血时,产生的tPA和uPA,remove,Coagulation & anticoagulation imbalance,Haemorrhage or thro
11、mbosis will appear when the balance between coagulation and anticoagulation is disturbed. Inappropriate clotting of blood can obstruct vital organ circulation. Systemic activation of coagulation in its most extreme form is known as disseminated intravascular coagulation (DIC).,正常凝血-抗凝平衡,凝血亢进,抗凝纤溶减弱,
12、凝血低下,抗凝或纤溶增强,继发性纤溶亢进 (凝血因子破坏,FDP生成),凝血因子消耗,血小板减少,DIC时凝血与抗凝血平衡紊乱的演变过程,Mechnism1: 组织因子释放,启动外源性凝血系统,Fribrin,Fibrinogen,FM,VIII,VIIIa,Ca2+,IXa,IX,Extrinsic pathway,创伤,烧伤,大手术,产科意外 肿瘤组织坏死,白血病细胞破坏。,Mechnism2: 血管内皮细胞损伤,损伤的VEC释放TF ,启动外源性凝血系统。 VEC的抗凝作用降低,TM-PC系统。 产生tPA减少,PAI-1增多,纤溶活性降低。 NO、PGI2、ADP酶产生减少,PLT粘
13、附和聚集的功能降低。 胶原暴露,激活,启动内源性凝血系统。,缺氧、酸中毒、内毒素、Ag-Ab,Mechnism3: 血细胞的大量破坏,血小板被激活,RBC破坏,释放大量ADP,促进血小板粘附,聚集。 WBC破坏释放TF样物质,WBC受刺激表达TF。 PLT激活、粘附、聚集,促进凝血。,异形输血、化疗,Mechnism4: 促凝物质释放入血,1.急性坏死性胰腺炎,胰蛋白酶入血激活凝血酶原 2.蛇毒激活,等,促进DIC发生 3.肿瘤细胞分泌促凝物质,严重感染引起DIC的发病机制,1,2,3,4,感染时产生的细胞因子作用于内皮细胞可使TF表达增加;而同时又可使内皮细胞上的TM、HS的表达明显减少 内
14、毒素可损伤血管内皮细胞,同时释放血小板激活剂,促进血小板的活化、聚集。 白细胞激活可释放炎症介质,损伤血管内皮细胞 细胞因子可使血管内皮细胞产生tPA减少,而PAI-1产生增多。,掌握和熟悉内容,1. Definition of DIC 2. Causes of DIC 3. Pathogenesis of DIC 4. Predisposing factors to DIC 5. Main clinical features of DIC 6. Types and stages of DIC 7. Treatment of DIC,Impairment of reticuloendothel
15、ial system,RES is a cleaner: Products of intravascular coagulation (free fibrin, prothrombinase, PF3). Various initiators of the process (endotoxin, tissue fragments, antigen-antibody complexes, thromboplastins, red cell stroma). The hepatic cells are of primary importance in the clearance of activa
16、ted coagulation factors (IXa, Xa and XIIa). The cleaner is too busy in DIC, various substances saturate or block the clearance function of reticuloendothelial system. (Shwartzman reaction in animals). Reticuloendothelial system is suppressd by glucocorticoid or in the patients with liver diseases.,H
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