DisseminatedIntravascularCoagulationPPT课件

Extrinsic pathway
VII/VIIa-TF-Ca2+
Fribrin
IX
IXa
VIIIa Ca2+
X
Xa
X
Va Ca2+
Thrombin
II
VIII
VIIIa FM
Ca2+
Fibrinogen
Mechnism2: 血管内皮细胞损伤
缺氧、酸中毒、内毒素、Ag-Ab
1. 损伤的VEC释放TF ，启动外源性凝血系统。 2. VEC的抗凝作用降低,TM-PC系统。 3. 产生tPA减少，PAI-1增多，纤溶活性降低。 4. NO、PGI2、ADP酶产生减少，PLT粘 附和聚集的功能降低。 5. 胶原暴露，激活Ⅻ，启动内源性凝血系统。
＋
Plasmin 纤溶酶
降解纤维蛋白 remove
水解凝血酶、凝血因子 -
PA inhibitor
Coagulation & anticoagulation imbalance
Haemorrhage or thrombosis will appear when the balance between coagulation and anticoagulation is disturbed.
Definition
Disseminated intravascular coagulation (DIC) is a complex systemic thrombohemorrhagic 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.
白血病干细胞的克隆性演化的遗传变异多样性。（2019-2019） 3．973子项目：肿瘤干细胞的动态演进及干预研究。（2019-2019）
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 reticuloendothelial system
RES is a cleaner: 1. Products of intravascular coagulation (free fibrin, prothrombinase, PF3). 2. Various initiators of the process (endotoxin, tissue fragments, antigen-antibody complexes, thromboplastins, red cell stroma). 3. The hepatic cells are of primary importance in the clearance of activated coagulation factors (IXa, Xa and XIIa).
Reticuloendothelial system is suppressd by glucocorticoid or in the patients with liver diseases.
DIC时凝血与抗凝血平衡紊乱的演变过程
凝血
抗凝
凝血系统激活
正常凝血-抗凝平衡
凝血因子消耗，血小板减少
继发性纤溶亢进 （凝血因子破坏，FDP生成）
凝血亢进，抗凝纤溶减弱
凝血低下，抗凝或纤溶增强
广泛微血栓形成
止、凝血功能障碍，出血倾向
Mechnism1: 组织因子释放，启动外源性凝血系统
创伤，烧伤，大手术，产科意外 肿瘤组织坏死，白血病细胞破坏。
Balance between coagulation and anti-coagulation
止血的过程 血管痉挛
血小板血栓形成
Coagulation
凝血
Anticoagulation
抗凝
纤维蛋白凝块形成
纤溶
stop remove
Fibrinolysis
Coagulation cascade
Intrinsic pathway
Cellular system: Monocyte/ Macrophage
Anticoagulants in plasma
1. ATⅢ,TFPI,heparin co-factor II
可灭活Ⅱa，Ⅶa，Ⅸa，Ⅹa，Ⅺa等; 凝血酶与血管内皮细胞表面肝素样物质结合，继而被AT- Ⅲ灭活
Protein C system
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
Coagulation Hypercoagulable state Thrombus
Fibrinolysis Hypocoagulable state Hemorrhage
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
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： 1. 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。（2019-2019） 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
KK PK
collagen HK
XII
XIIa
Extrinsic pathway
VII/VIIa-TF-Ca2+
XI
XIa
Fribrin
IX
IXa
VIIIa Ca2+
X
Xa
X
Va Ca2+
Thrombin
II
VIII
VIIIa FM
Ca2+
Fibrinogen
Coagulation cascade
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、 Cell 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 2019)，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。
Intrinsic pathway
KK PK
collagen HK
XБайду номын сангаасI
XIIa
Extrinsic pathway
VII/VIIa-TF-Ca2+
XI
XIa
Fribrin
IX
IXa
VIIIa Ca2+
X
Xa
X
Va Ca2+
Thrombin
II
VIII
VIIIa FM
Ca2+
Fibrinogen
Anti-coagulation
DisseminatedIntravascularCoagulationPPT课件
洪登礼 研究员 医学干细胞研究组组长
教育经历： 1992，武汉同济医科大学临床医学本科。 2019，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： 2019-2000武汉 同济医科大学附属同济医院血液内科医师。 2000-2019 意大利都灵大学IRCC肿瘤研究所博士后。 2019-2019 英国牛津大学WIMM分子医学研究所助理研究员。 2019-2009 英国牛津大学WIMM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。
Diseases associated with DIC
Sepsis/severe infection 30% Malignancy 25%
solid and myeloproliferative malignancies Obstetric complications 20%
Amniotic fluid embolism, 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
Mechnism3: 血细胞的大量破坏，血小板被激活
异形输血、化疗 1. RBC破坏，释放大量ADP，促进血小板粘附，聚集。 2. WBC破坏释放TF样物质，WBC受刺激表达TF。 3. PLT激活、粘附、聚集，促进凝血。
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Ⅴ，Ⅹ等，促进DIC发生 3.肿瘤细胞分泌促凝物质
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).
严重感染引起DIC的发病机制
1 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
2 内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。
3 白细胞激活可释放炎症介质，损伤血管内皮细 胞
4 细胞因子可使血管内皮细胞产生tPA减少，而 PAI-1产生增多。
Triggering factors
① Release TF ② VEC injury ③ LPS ④ Ag-Ab complex
⑤ Protease ⑥ Microparticles ⑦ 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
The cleaner is too busy in DIC, various substances saturate or block the clearance function of reticuloendothelial system. (Shwartzman reaction in animals).
Protein C system
蛋白C
激活的蛋白C（APC）
＋
＋
凝血酶
蛋白S
血栓调节蛋白TM
内皮细胞
灭活Ⅴa，Ⅷa
Fibrinolytic system
Plasminogen
内源性凝血时,PK分解产生激肽
Plasminogen activators PA
释放酶 外源性凝血时,产生的tPA和uPA