DIC弥漫性血管内凝血-北京协和医院血液科.ppt

DIC的诊断与治疗的诊断与治疗 北京协和医院血液科 DICDIC的定义的定义 D Disseminated isseminated I Intravascular ntravascular C Coagulationoagulation DIC是一种发生于多种疾病或特殊病理状态下，人体凝血系统被激活而引起中小血管内弥漫性微血栓形成及继发性纤溶亢进的综合征。由于DIC发展过程中出现不同程度的血小板和凝血因子水平消耗性减少，也称之为“消耗性凝血病”或“消耗性血栓出血性疾病”。Clinical conditions associated with DIC 1.Sepsis/Severe infection-44.6%2.Malignancy-20.7%Solid tumors 6.9%，AL 13.8%.Occurrence in APL 3765%.3.Obstetrical calamities-13.4%Amniotic fluid embolism,Abruptio placentae,Dead fetus 4.Trauma/Surgery-7.4%5.Severe hepatic failure-7.4%6.Vascular abnormalities Kasabach-Merritt syndrome，Large vascular aneurysms 7.Organ destruction(e.g.,severe pancreatitis)8.Severe toxic or immunologic reactions Snake bites，Recreational drugs，Transfusion reactions，Transplant rejection Mortality DIC-Death Is Coming.Mortality ranges from 3186%,whether or not heparin was administrated.Correlated Factors:Underlying disorders The extent of orgon dysfuction The degree of hemostatic failure Increasing age Contact Factor PathwayTissue Factor Pathway(Intrinsic Pathway)(Extrinsic Pathway)Kallikrein Prekallikrein“Tissue Damage”XIIXIIaTissue FactorHKC-1 InhibitorXIXIaIXCa+Ca+VIIIVIIIaIIaIIIIaVaVProtein CAPCProtein SPC InhibitorTMSKIIaIIaFibrinogenFibrin MonomerAT-IIIHCF-IIFibrin PolymerFibrin ClotFDPXIIIaCa+Plasmin2 AntiplasminPlasminogenUKt-PAPAI-1Fibrinolysis SystemCoagulation and Fibrinolysis(VIIa)XaIXaCa+PLXaXVIIaVIITFPICa+PLXIIIIIaCa+Ca+PLCa+PLThe Simplified Mechanism of DIC DIC的失调控 Sepsis、Cancer、Trauma、Obstetrical complications:TF Liver Disease:AT-III、PC/PS Sepsis:TM、PC Pregnancy:PS APL、Amniotic Fluid Embolism、Prostate Cancer:Plasmin Thrombin Explosion under Pathological Conditions IXa(+VIII)Xa(+V)TF+VIIa Thrombin Fibrinogen Fibrin Decrease of AT-III Impairment of PC System Insufficient TFPI Cytokines(IL-6,etc.)Plasminogen Plasmin Fibrin FDPs PA PAI-1 Generation of Thrombin Mediated by TF Impairment of Anticoagulation Pathway Suppression of Fibrinolysis by PAI-1 Formation of Fibrin Inadequate Removal of Fibrin Thrombosis of Small and Midsize Vessels Pathogenetic Pathways Involved in DIC Abnormal Coagulation in DIC Physiologic Anticoagulant Pathways Dysfunction of the PC System in DIC Schistocytes Intravascular Fibrin DIC临床表现频率临床表现频率 临床表现各异，根据6组报道平均发生率 (Williams Hematology-6th Edition，Table 126-2)1.出血表现：77.3%2.肾损害：46.4%3.呼吸道表现：42.2%4.肝损害：39.5%5.休克：34.5%6.CNS表现：22.8%7.血栓栓塞：22.2%8.肢端苍白：6.8%9.其它 DIC的实验室检查 Markers of Thrombin Generation D-dimer 3P test Fibrin monomer Fibrinopeptide A Prothrombin fragment 1+2 TAT Screening assays for factors and platelet consumption PT APTT TT Fibrinogen Platelet count Ancillary tests FDP ELT AT-III Factor V/VIII 2-Antiplasmin DICDIC的诊断标准的诊断标准 根据1994年武汉全国出血与血栓学术讨论会拟订以下标准：1.临床表现 2.实验室指标 临床表现临床表现 1 1、存在易引起、存在易引起DICDIC的基础疾病。的基础疾病。2 2、有下列两项以上的临床表现、有下列两项以上的临床表现 多发性出血倾向。不易用原发病解释的微循环衰竭或休克。多发性微血管栓塞的症状、体征，如皮肤、皮下、粘膜栓塞坏死及早期出现的肾、肺、脑等脏器功能不全。抗凝治疗有效。实验室主要标准实验室主要标准 -同时有以下三项以上异常同时有以下三项以上异常 1.Plt.100109/L或进行性下降（肝病、白血病血小板50109/L）或有2项以上血小板活化产物升高（-TG,PF4,TXB2，GMP-140）。2.血浆Fibrinogen含量1.5g/L（白血病及其他恶性肿瘤1.8g/L，肝病4g/L。3.3P(+)或血浆FDP20mg/L（肝病FDP60mg/L），或D-Dimer升高。实验室主要标准（续）实验室主要标准（续）4.PT时间缩短或延长3s以上或呈动态变化（肝病时PT延长5s以上）。5.周围血破碎RBC 2%。对疑难病例、需另查：对疑难病例、需另查：1.Plasminogen含量及活性降低。2.AT-III含量及活性降低（不适用于肝病）。3.血浆因子VIII:C活性50%（肝病须具备）。DICDIC实验室诊断最低标准实验室诊断最低标准 (适于基层医院适于基层医院)同时有下列三项以上异常同时有下列三项以上异常 1.血小板100109/L或进行性下降。2.血浆Fibrinogen含量20mg/L。4.PT缩短或延长3s以上或呈动态变化。5.周围血破碎红细胞2%。附：白血病合并附：白血病合并DICDIC的实验室标准的实验室标准 1.血小板计数低于50109/L或进行性下降，或有2项以上血浆血小板活化产物升高:-TG；PF4；TXB2；GMP-140。2.血浆Fibrinogen含量20mg/L或D-Dimer水平升高。4.PT缩短或延长3s以上或呈动态变化。5.Plasminogen含量及活性降低。附：肝病合并附：肝病合并DICDIC的实验室标准的实验室标准 1.血小板50109/L或有2项以上血浆血小板活化产物升高:-TG；PF4；TXB2；GMP-140。2.血浆Fibrinogen含量1.0g/L。3.血浆FVIII:C活性60mg/L或D-Dimer水平升高。慢性慢性DICDIC 在转移癌、肝病、SLE、巨大血管瘤或死胎滞留综合征等情况下，慢性持续或间歇性启动血管内凝血引发的DIC。栓塞较出血常见。实验室：血小板数轻度减少。Fibrinogen正常或升高。PT、APTT可能正常。FDPs、D-Dimer升高。破碎RBC常见、但程度逊于TTP者。Diagnostic algorithm for overt DIC-ASH 2002 1.Risk assessment:Does the patient have a underlying disorder known to be associated with overt DIC?If yes,proceed.If no,do not use this algorithm.2.Order global coagulation tests(platelet count,prothrombin time PT,fibrinogen,soluble fibrin monomers,or fibrin degradation products).3.Score global coagulation test results:platelet count-(100=0,100=1,50=2)elevated fibrin-related marker(e.g.,soluble fibrin-monomers/fibrin degradation products)(no increase=0,moderate increase=2,strong increase=3)prolonged prothrombin time-(3 but 6 sec.=2)fibrinogen level-(1.0 g/L=0,1.0 g/L=1)4.Calculate score.-5.If 5:compatible with overt DIC;repeat scoring daily.If 120分钟。当Fg1.0g/L时可有假阳性。ELT变化的意义：变化的意义：ELT缩短：见于纤溶亢进（原发或继发）。ELT延长：表明纤溶活性减低，可见于血栓前状态或血栓性疾病。DICDIC与重症肝病的鉴别与重症肝病的鉴别 DICDIC重症肝病重症肝病微循环衰竭早，多见晚，少见黄疸轻，少见重，多见肾功能损伤早，多见晚，少见RBC 破坏多见（50-90%）罕见FVIII:C降低正常Plt 活化及代谢产物 增加多正常FDP明显增加正常或轻度增加D-Dimer增加正常或轻度增加DICDIC与与TTPTTP鉴别鉴别 DICDICTTPTTP起病及病程多急骤，病程短可急可缓，病程长微循环衰竭多见少见黄疸轻，少见多见，较重FVIII:C减少正常PC 含量及活性减少正常FDP增加正常D-Dimer增加正常血栓性质Fibrin 血栓为主血小板血栓为主DICDIC伴原发纤溶亢进伴原发纤溶亢进 凝血和纤溶被同时激活凝血和纤溶被同时激活，既Thrombin与Plasmin独立生成。与与DIC继发纤溶鉴别困难继发纤溶鉴别困难，但DIC伴原发纤溶亢进多发生于APL、热休克、转移性前列腺癌、