DisseminatedIntravascularCoagulaionPPT課件

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:mail: http:/ 研究員研究員 醫(yī)學(xué)干細(xì)胞研究組組長醫(yī)學(xué)干細(xì)胞研究組組長 貢獻(xiàn)：貢獻(xiàn)：致力于研究

2、干細(xì)胞疾病中干細(xì)胞在生理和病理性niche中的功能和基因組穩(wěn)定性及克隆性演化。成果發(fā)表在science、 cell stem cell和 jci等雜志。 最重要的貢獻(xiàn)是，第一次鑒定了前白血病干細(xì)胞（hong d, et al. science 2008)，被認(rèn)為是腫瘤研究的重大突破，延伸研究提出了腫瘤干細(xì)胞的克隆性演化模型。 教育經(jīng)歷：教育經(jīng)歷： 1992，武漢同濟(jì)醫(yī)科大學(xué)臨床醫(yī)學(xué)本科。 1998，武漢同濟(jì)醫(yī)科大學(xué)血液內(nèi)科研究生。 2009，牛津大學(xué)分子醫(yī)學(xué)研究所哲學(xué)博士。工作簡歷工作簡歷： 1998-2000武漢同濟(jì)醫(yī)科大學(xué)附屬同濟(jì)醫(yī)院血液內(nèi)科醫(yī)師。2000-2003意大利都靈大學(xué)ircc腫

3、瘤研究所博士后。2003-2006英國牛津大學(xué)wimm分子醫(yī)學(xué)研究所助理研究員。2006-2009英國牛津大學(xué)wimm分子醫(yī)學(xué)研究所研究員。2009-今上海交大醫(yī)學(xué)科學(xué)研究院/細(xì)胞分化與凋亡教育部重點(diǎn)實(shí)驗(yàn)室研究員， 醫(yī)學(xué)干細(xì)胞組組長。醫(yī)學(xué)干細(xì)胞研究組醫(yī)學(xué)干細(xì)胞研究組歡迎你！歡迎你！ 研究方向：研究方向：1. 1.干細(xì)胞干細(xì)胞在腫瘤起始和發(fā)展過程中的在腫瘤起始和發(fā)展過程中的克隆性演化克隆性演化和和表觀遺傳調(diào)控。表觀遺傳調(diào)控。2. 2.造血造血干細(xì)胞干細(xì)胞在生理和病理性在生理和病理性niche中的功能和基因組穩(wěn)定性。中的功能和基因組穩(wěn)定性。3. 3. 重編程干細(xì)胞重編程干細(xì)胞在醫(yī)學(xué)上的應(yīng)用。在醫(yī)學(xué)

4、上的應(yīng)用。正在承擔(dān)的研究項(xiàng)目：正在承擔(dān)的研究項(xiàng)目：1.國家自然基金重大研究計(jì)劃培育項(xiàng)目：tel-aml1啟動(dòng)的干細(xì)胞克隆性演化的表觀遺傳調(diào)控機(jī)制。（2010-2012） 2國家自然科學(xué)基金重大國際合作研究項(xiàng)目：bcr-abl 相關(guān)急性淋巴細(xì)胞白血病干細(xì)胞的克隆性演化的遺傳變異多樣性。（2012-2016）3973子項(xiàng)目：腫瘤干細(xì)胞的動(dòng)態(tài)演進(jìn)及干預(yù)研究。（2012-2016）掌握掌握和和熟悉熟悉內(nèi)容內(nèi)容 1. definition of dic 2. causes of dic 3. pathogenesis of dic 4. predisposing factors to dic5. mai

5、n clinical features of dic6. 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

6、of fibrinolysis. the resultant 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內(nèi)容內(nèi)容 1. definition of dic 2. causes of dic 3. pathogenesis of dic 4. predisposing factors to d

7、ic5. main clinical features of dic6. 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 ntr

8、auma (neurotrauma) ,organ destruction, burns 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內(nèi)容內(nèi)容 1. definition of dic 2. causes of dic 3. pathogenesis of di

9、c 4. predisposing factors to dic5. main clinical features of dic6. types and stages of dic7. treatment of dic balance between coagulation and anti-coagulation anti-coagulationfibrinolysiscoagulation 抗凝抗凝凝血凝血纖溶纖溶 coagulation cascade xxaxfribrinfibrinogenfmviiiviiiaca2+vii/viia-tf-ca2+xiixiiapkkkcolla

10、genhkxixiaviiiaca2+ixaixintrinsic pathway vaca2+thrombin iiextrinsic pathway coagulation cascade xxaxfribrinfibrinogenfmviiiviiiaca2+vii/viia-tf-ca2+xiixiiapkkkcollagenhkxixiaviiiaca2+ixaixintrinsic pathway vaca2+thrombin iiextrinsic pathway anti-coagulation n cellular system: monocyte/ macrophagen

11、anticoagulants in plasma1. at,tfpi,heparin co-factor ii 可滅活可滅活a，a，a，a，a等等; 凝血酶與血管內(nèi)皮細(xì)胞表面肝素樣物質(zhì)結(jié)合，繼而被凝血酶與血管內(nèi)皮細(xì)胞表面肝素樣物質(zhì)結(jié)合，繼而被at- 滅活滅活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）滅活滅活aa，aa蛋白蛋白s s內(nèi)皮細(xì)胞內(nèi)皮細(xì)胞血栓調(diào)節(jié)蛋白血栓調(diào)節(jié)蛋白tmtm凝血酶凝血酶 fibrinolytic system plasminogenplasmin 纖溶酶纖溶酶coagulation &am

12、p; anticoagulation imbalance n haemorrhage or thrombosis will appear 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 in

13、travascular coagulation (dic).凝血系統(tǒng)激活凝血系統(tǒng)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血亢進(jìn)，抗凝纖溶減弱凝血亢進(jìn)，抗凝纖溶減弱凝血低下，抗凝或纖溶增強(qiáng)凝血低下，抗凝或纖溶增強(qiáng) 繼發(fā)性纖溶亢進(jìn)繼發(fā)性纖溶亢進(jìn)（凝血因子破壞，（凝血因子破壞，fdp生成）生成）廣泛廣泛微血栓微血栓形成形成止、凝血功能障礙，出血傾向止、凝血功能障礙，出血傾向凝血因子消耗，血小板減少凝血因子消耗，血小板減少dic時(shí)凝血與抗凝血平衡紊亂的演變過程時(shí)凝血與抗凝血平衡紊亂的演變過程 mechnism1: 組織因子釋放，啟動(dòng)外源性凝血系統(tǒng)組織因子釋放，啟動(dòng)外源性凝血系統(tǒng)xx

14、axfribrinfibrinogenfmviiiviiiaca2+vii/viia-tf-ca2+viiiaca2+ixaixvaca2+thrombin iiextrinsic pathway 創(chuàng)傷，燒傷，大手術(shù)，產(chǎn)科意外創(chuàng)傷，燒傷，大手術(shù)，產(chǎn)科意外腫瘤組織壞死，白血病細(xì)胞破壞。腫瘤組織壞死，白血病細(xì)胞破壞。 mechnism2: 血管內(nèi)皮細(xì)胞損傷血管內(nèi)皮細(xì)胞損傷 mechnism3: 血細(xì)胞的大量破壞，血小板被激活血細(xì)胞的大量破壞，血小板被激活1. rbc破壞，釋放大量破壞，釋放大量adp，促進(jìn)血小板粘附，聚集。，促進(jìn)血小板粘附，聚集。2. wbc破壞釋放破壞釋放tf樣物質(zhì)，樣物質(zhì)，wb

15、c受刺激表達(dá)受刺激表達(dá)tf。3. plt激活、粘附、聚集，促進(jìn)凝血。激活、粘附、聚集，促進(jìn)凝血。 mechnism4: 促凝物質(zhì)釋放入血促凝物質(zhì)釋放入血嚴(yán)重感染引起嚴(yán)重感染引起dic的發(fā)病機(jī)制的發(fā)病機(jī)制1234掌握掌握和和熟悉熟悉內(nèi)容內(nèi)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 o

16、f reticuloendothelial system n 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 importanc

17、e in the clearance of activated coagulation factors (ixa, xa and xiia). n the cleaner is too busy in dic, 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

18、patients with liver diseaseshepatic dysfunction hemostasis is intimately related to liver function, because 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 co

19、agulation abnormalities depends upon the degree of disturbed liver function. n acute or chronic hepatocellular 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 fa

20、ilure may present with the entire spectrum of factor deficiencies and may even develop dic. n patients with liver cirrhosis 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 impai

21、red protein synthesis. abnormal fibrinogen and prothrombin molecules can be identified. platelets are quantitatively and 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 a

22、nd x, etc.) in blood are increased, while the substances with the action of anticoagulation and with the activity of fibrinolysis 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

23、the incidence of dic is elevated in obstetrical accidents. 2. acidosis, common in some patients, promotes the activation of clotting cascade by reducing the ph of the blood.disorder of microcirculation n shock usually accompanies disorder of microcirculation permitting activated clotting factors to

24、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 of sludging, n the stasis of blood in giant hemangioma may somehow contribute to the development of dic.inhibition of fibrinolysis n aging, smoking, diabete

25、s.n using antifibrinolytic agents. 掌握掌握和和熟悉熟悉內(nèi)容內(nèi)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 dicbleeding n include:1. petechiae and purpura (found in most patients), hemorrhagic

26、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 venipuncture sites or intraarterial lines is another common finding. 4. large subcutaneous hematomas and deep tissue bleeding are also o

27、ften seen.1. bleeding causes: clotting factors consumption fdp generation activation of fibrinolytic system vessel damageof consumption, secondary.shock nexcess bleedingnthrombus formation results in a diminished return of venous blood to the heartnactivation of the kinin(激肽）system leads to increase

28、d vascular permeability, hypotension, and shockncreation of fdp result in enhanced vasodilationnmyocardial infarctionend-organ damage / failure nimpaired blood flow caused by microvascular thrombosisnischemia reperfusion injurynsystemic inflammatory response syndrom nmultiple organ dysfunction syndr

29、omepathogenesislkidneys renal damage seen in 25% of dic cases in one serieslliver hepatic dysfunction in 19%llungs respiratory dysfunction in 16%microangiopathic hemolytic anemia 裂體細(xì)胞掌握掌握和和熟悉熟悉內(nèi)容內(nèi)容 1. definition of dic 2. causes of dic 3. pathogenesis of dic 4. predisposing factors to dic5. main cli

30、nical features of dic6. types and stages of dic7. treatment of dic促凝物質(zhì)促凝物質(zhì)纖溶活性纖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 繼發(fā)性纖溶亢進(jìn)期繼發(fā)性纖溶亢進(jìn)期lab凝血時(shí)間、pt血小板粘附性血小板數(shù)纖維蛋白原血栓（+）出、凝血時(shí)間pt血小板凝血因子纖溶活性/n纖溶活性（優(yōu)球蛋白溶解時(shí)間）纖溶酶原3p 試驗(yàn)（+）stages plasma protamine paracoagulation d-dimer formationtypes n acute decompensated dicn ch

31、ronic 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 to 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