DisseminatedIntravascularCoagulationPPT课件

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1、1 Disseminated Intravascular Coagulation(DIC)Dengli Hong MD PhDGroup head of medical stem cell biologyShanghai Jiao-Tong University School of MedicineKey Lab of Cell Differentiation and Apoptosis of Chinese Ministry of Education TEL:021-64666992EMAIL:http:/ 研究员研究员 医学干细胞研究组组长医学干细胞研究组组长 贡献：贡献：致力于研究干细胞

2、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 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：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

3、-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。医学干细胞研究组医学干细胞研究组欢迎你！欢迎你！研究方向：研究方向：1.1.干细胞干细胞在肿瘤起始和发展过程中的在肿瘤起始和发展过程中的克隆性演化克隆性演化和和表观遗传调控。表观遗传调控。2.2.造血造血干细胞干细胞在生理和病理性在生理和病理性niche中的功能和基因组稳定性。中的功能和基因组稳定性。3.3.重编程干细胞重编程干细胞在医学上的应用。在医学上的应用。正在承担的研究项目：正在承

4、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。（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）3973子项目：肿瘤干细胞的动态演进及干预研究。（2012-2016）掌握掌握和和熟悉熟悉内容内容 1.Definition of DIC 2.Causes of DIC 3.Pathogenesis of DIC 4.Predisposing factors to DIC5.Main clinical features of D

5、IC6.Types and stages of DIC7.Treatment of DICDefinition 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

6、clinical condition is characterized by intravascular coagulation and hemorrhageCoagulation Hypercoagulable state ThrombusFibrinolysis Hypocoagulable state Hemorrhage掌握掌握和和熟悉熟悉内容内容 1.Definition of DIC 2.Causes of DIC 3.Pathogenesis of DIC 4.Predisposing factors to DIC5.Main clinical features of DIC6.

7、Types and stages of DIC7.Treatment of DICDiseases associated with DIC nSepsis/severe infection 30%nMalignancy 25%solid and myeloproliferative malignancies nObstetric complications 20%Amniotic fluid embolism,Abruptio placentae Retained dead fetus syndrome nTrauma(neurotrauma),Organ destruction,Burns

8、15%nSevere hepatic failurenRheumatologic illness Adult Stills disease,Lupus nVascular abnormalities Kasabach-Merritt syndrome,Large vascular aneurysmsnHemolysisTriggering factors 掌握掌握和和熟悉熟悉内容内容 1.Definition of DIC 2.Causes of DIC 3.Pathogenesis of DIC 4.Predisposing factors to DIC5.Main clinical fea

9、tures of DIC6.Types and stages of DIC7.Treatment of DIC Balance between coagulation and anti-coagulation Anti-coagulationFibrinolysisCoagulation 抗凝抗凝凝血凝血纤溶纤溶 Coagulation cascade XXaXFribrinFibrinogenFMVIIIVIIIaCa2+VII/VIIa-TF-Ca2+XIIXIIaPKKKcollagenHKXIXIaVIIIaCa2+IXaIXIntrinsic pathway VaCa2+Thromb

10、in IIExtrinsic pathway Coagulation cascade XXaXFribrinFibrinogenFMVIIIVIIIaCa2+VII/VIIa-TF-Ca2+XIIXIIaPKKKcollagenHKXIXIaVIIIaCa2+IXaIXIntrinsic pathway VaCa2+Thrombin IIExtrinsic pathway Anti-coagulation n Cellular system:Monocyte/Macrophagen Anticoagulants in plasma1.AT,TFPI,heparin co-factor II 可

11、灭活可灭活a，a，a，a，a等等;凝血酶与血管内皮细胞表面肝素样物质结合，继而被凝血酶与血管内皮细胞表面肝素样物质结合，继而被AT-灭活灭活2.Protein C systemProtein C system 蛋白蛋白C C激活的蛋白激活的蛋白C C（APCAPC）灭活灭活aa，aa蛋白蛋白S S内皮细胞内皮细胞血栓调节蛋白血栓调节蛋白TMTM凝血酶凝血酶 Fibrinolytic system PlasminogenPlasmin 纤溶酶纤溶酶Coagulation&anticoagulation imbalance n Haemorrhage or thrombosis will appe

12、ar when the balance between coagulation and anticoagulation is disturbed.n Inappropriate clotting of blood can obstruct vital organ circulation.n Systemic activation of coagulation in its most extreme form is known as disseminated intravascular coagulation(DIC).凝血系统激活凝血系统激活凝血凝血抗凝抗凝正常凝血正常凝血-抗凝平衡抗凝平衡凝

13、血亢进，抗凝纤溶减弱凝血亢进，抗凝纤溶减弱凝血低下，抗凝或纤溶增强凝血低下，抗凝或纤溶增强 继发性纤溶亢进继发性纤溶亢进（凝血因子破坏，（凝血因子破坏，FDP生成）生成）广泛广泛微血栓微血栓形成形成止、凝血功能障碍，出血倾向止、凝血功能障碍，出血倾向凝血因子消耗，血小板减少凝血因子消耗，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组织因子释放，启动外源性凝血系统XXaXFribrinFibrinogenFMVIIIVIIIaCa2+VII/VIIa-TF-Ca2+VIIIaCa2+IXaIXVaCa2+T

14、hrombin IIExtrinsic pathway 创伤，烧伤，大手术，产科意外创伤，烧伤，大手术，产科意外肿瘤组织坏死，白血病细胞破坏。肿瘤组织坏死，白血病细胞破坏。Mechnism2:血管内皮细胞损伤血管内皮细胞损伤 Mechnism3:血细胞的大量破坏，血小板被激活血细胞的大量破坏，血小板被激活1.RBC破坏，释放大量破坏，释放大量ADP，促进血小板粘附，聚集。，促进血小板粘附，聚集。2.WBC破坏释放破坏释放TF样物质，样物质，WBC受刺激表达受刺激表达TF。3.PLT激活、粘附、聚集，促进凝血。激活、粘附、聚集，促进凝血。Mechnism4:促凝物质释放入血促凝物质释放入血严重感

15、染引起严重感染引起DIC的发病机制的发病机制1234掌握掌握和和熟悉熟悉内容内容 1.Definition of DIC 2.Causes of DIC 3.Pathogenesis of DIC 4.Predisposing factors to DIC5.Main clinical features of DIC6.Types and stages of DIC7.Treatment of DICImpairment of reticuloendothelial system n RES is a cleaner:1.Products of intravascular coagulatio

16、n(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).n The cleaner is too busy in D

17、IC,various substances saturate or block the clearance function of reticuloendothelial system.(Shwartzman reaction in animals).n Reticuloendothelial system is suppressd by glucocorticoid or in the patients with liver diseasesHepatic dysfunction Hemostasis is intimately related to liver function,becau

18、se most coagulation factors are synthesized by liver parenchymal cells and the livers reticuloendothelial system serves an important role in the clearance of activation products.The extent of coagulation abnormalities depends upon the degree of disturbed liver function.n Acute or chronic hepatocellu

19、lar diseases may display decreases in the vitamin K-dependent factors(prothrombin;factors VII,IX,and X;proteins C and S),whereas other parameters remain normal.n Patients with hepatic failure may present with the entire spectrum of factor deficiencies and may even develop DIC.n Patients with liver c

20、irrhosis have a wide spectrum of abnormalities.Except for factor VIII:C and von Willebrand factor,all procoagulant and inhibitory factors are decreased,which is a reflection of impaired protein synthesis.Abnormal fibrinogen and prothrombin molecules can be identified.Platelets are quantitatively and

21、 qualitatively altered,and most patients develop DIC.Hypercoagulable state Hypercoagulable state:the platelet and several kinds of clotting factors(factor I,II,VII,VIII,IX and X,etc.)in blood are increased,while the substances with the action of anticoagulation and with the activity of fibrinolysis

22、are deceased.For instance,1.The blood in pregnancy after 4 months bigins to increase coagulability,which is most marked in the terminal stage of pregnancy.Therefore the incidence of DIC is elevated in obstetrical accidents.2.Acidosis,common in some patients,promotes the activation of clotting cascad

23、e by reducing the pH of the blood.Disorder of microcirculation n Shock usually accompanies disorder of microcirculation permitting activated clotting factors to accumulated in one region making it easier to develop into a state of DIC:1.stasis of blood flow,2.aggregation of blood cells 3.appearance

24、of sludging,n The stasis of blood in giant hemangioma may somehow contribute to the development of DIC.Inhibition of fibrinolysis n Aging,smoking,diabetes.n Using antifibrinolytic agents.掌握掌握和和熟悉熟悉内容内容 1.Definition of DIC 2.Causes of DIC 3.Pathogenesis of DIC 4.Predisposing factors to DIC5.Main clin

25、ical features of DIC6.Types and stages of DIC7.Treatment of DICBleeding n Include:1.petechiae and purpura(found in most patients),hemorrhagic bullae,wound bleeding;2.especially oozing from a surgical or traumatic wound is common in patients who have undergone surgery or suffered trauma.3.Oozing from

26、 venipuncture sites or intraarterial lines is another common finding.4.Large subcutaneous hematomas and deep tissue bleeding are also often seen.1.Bleeding causes:Clotting factors consumption FDP generation Activation of fibrinolytic system Vessel damageOf consumption,secondary.Shock nExcess bleedin

27、gnThrombus formation results in a diminished return of venous blood to the heartnActivation of the kinin(激肽）system leads to increased vascular permeability,hypotension,and shocknCreation of FDP result in enhanced vasodilationnMyocardial infarctionEnd-organ damage/failure nImpaired blood flow caused

28、by microvascular thrombosisnIschemia reperfusion injurynSystemic inflammatory response syndrom nMultiple organ dysfunction syndromePathogenesislKidneys renal damage seen in 25%of DIC cases in one serieslLiver hepatic dysfunction in 19%lLungs respiratory dysfunction in 16%Microangiopathic hemolytic a

29、nemia 裂体细胞掌握掌握和和熟悉熟悉内容内容 1.Definition of DIC 2.Causes of DIC 3.Pathogenesis of DIC 4.Predisposing factors to DIC5.Main clinical features of DIC6.Types and stages of DIC7.Treatment of DIC促凝物质促凝物质纤溶活性纤溶活性血液凝固性血液凝固性分期分期高凝期高凝期消耗性低凝期消耗性低凝期 继发性纤溶亢进期继发性纤溶亢进期Lab凝血时间、PT血小板粘附性血小板数纤维蛋白原血栓（+）出、凝血时间PT血小板凝血因子纤溶活性

30、/N纤溶活性（优球蛋白溶解时间）纤溶酶原3P 试验（+）Stages Plasma Protamine Paracoagulation D-dimer formationTypes n Acute decompensated DICn Chronic compensated DICCompensated DIC:When the stimulus for coagulation is mild,the liver can increase production of clotting factors to up to 5 times the normal rate,in an effort t

31、o maintain plasma levels.Similarly,platelet production can increase up to 10 times.Thus,although coagulation and fibrinolysis are in progress,platelet counts and fibrinogen levels may be normal or only marpinally reduced.These patients rarely bleed spontaneously or from minor trauma,but have severe

32、haemorrhage if subjected to surgery.掌握掌握和和熟悉熟悉内容内容 1.Definition of DIC 2.Causes of DIC 3.Pathogenesis of DIC 4.Predisposing factors to DIC5.Main clinical features of DIC6.Types and stages of DIC7.Treatment of DICTreatments Cornerstone of management is the treatment of the underlying illnessSupportiv

33、e management with Disruption of coagulation cascade using“lower dose”heparin-treatment,administration of ATIII and/or activated protein C(protein C infusion has shown to be the first intervention proven to be effective in reducing the mortality in septic patients If bleeding is the predominant sympt

34、om Platelet infusion Coagulation factor substitution with fresh frozen plasmaSummary Primary diseasestissue injuryVEC damageBlood cells injuryothersTF or other procoagulant components releasingActivate coagulation cascadeFibrin depositthrombosisSecondary fibrinolysisBleedingShockHemolytic AnemiaMODSFDP formationClotting factors consumptionHypocoagulableHypercoagulable医学干细胞研究组医学干细胞研究组欢迎你！欢迎你！Email to me:洪登礼