1、Disseminated Intravascular CoagulationHuang HonghuiDept. of Hematology, Renji HospitalDefinitionDIC: clinicopathologic syndrome widespread intravascular coagulation is induced by procoagulants that are introduced into or produced in the blood circulation and overcome the natural anticoagulant mechan
2、isms.EtiologyStage of hypercoagulabilityStage of hypocoagulabilityStage of secondary fibrinolysisPathophysiologyStage of hypercoagulabilityStage of hypocoagulability due to excess of consumption of blood coagulation factorsStage of secondary fibrinolysisTyping of DICClinical featuresBleedingThromboe
3、mbolismCirculatory disturbance, shockMicroangiopathic hemolytic anemiaClinical featuresBleedingMechanismconsumption of hemostatic components including platelets, fibrinogen, and other coagulation factors;secondary fibrinolysis;anticoagulant effects of fibrinogen/fibrin degradation products;manifesta
4、tionsSkin and mucosa:petechiae, ecchymosis, oozing from veni-punctures, arterial lines, catheters, and injured tissues;internal organ:massive bleeding into the gastrointestinal, lungs, central nervous system, or orbit.Clinical featuresThromboembolism三、器官功能障碍DIC时，器官功能障碍主要由于微血栓大量形成！肺-呼吸功能障碍肾-肾功能障碍心-心泵
5、功能障碍肾上腺皮质-华-佛综合症垂体-席汉综合症心肌中的微血栓肝内微血栓肾 内 微 血 栓（纤 维 蛋 白 特 殊 染 色 ）肺 泡肺 内 微 血 栓Clinical features Circulatory disturbance, shock a kininogen kallidini formation of Fibrinopeptide A microvascular thrombi Fibrinopeptide B thrombin dilatation of the blood vessles returned blood volume vasospasm hemorrhageSH
6、OCKcirculating blood volume diseases underlying DIC Clinical featuresMicroangiopathic hemolytic anemiaMechanismErythrocytes are injured mechanically during passage through fibrin networks in the microcirculation. Manifestationproduction of schistocytes and microspherocytes;jaundice, hemoglobinuria,
7、anemia.Direction ofblood flowFibrinRBC悬挂在纤维蛋白索上（扫描电镜，左2000，右5200）Laboratory featuresBasic blood examinationsPlatelet count: BPC Peripheral blood smear: schistocytes (in approximately 50% of cases)Laboratory featuresThe coagulation defectPartial thromboplastin time (PTT)Prothrombin timeThrombin timeF
8、ibrinogen concentrationLaboratory featuresTests for fibrinolysisFibrinogen degradation products (FDP)D-dimerPlasma protamine paracoagulation test (3P)Euglobulin lysis timeLaboratory featuresOther laboratory findings(molecular markers)F1+2Thrombin-AT complex (TAT)Fibrinopeptide A (FPA)SFMC (soluble f
9、ibrin monomer complex) Antithrombin Products of platelet activation:-TG,PF-4,TXB2,GMP-140PIC (plasmin-2 plasmin inhibitor complex) aprothrombin +AT TAT F1+2fibrinogenfibrin monomerFPA,FPBPolymerizationsoluble fibrinplasminaFDPcross-linked fibrinSFMC: FDP(X)+FM+FgLaboratory featuresLaboratory data ch
10、ange with remarkable rapidity in DIC, and in doubtful cases, it is often important to repeat the tests at frequent intervals, even every 8 to 12 hours and observing the dynamics of the process.Diagnostic criteria - ISTH DIC score1.Risk assessment: does the patient have an underlying disorder known t
11、o be associated with overt DIC?If yes: Proceed.If no: Do not use this algorithm.2. Order global coagulation testsplatelet count, prothrombin time,fibrinogen, fibrin-related marker3. Score global coagulation test results. Platelet count(100 = 0; 100 = 1; 50 = 2) Elevated fibrin related marker (e.g. D
12、-dimers; fibrin degradation products)(no increase = 0; moderate increase = 2; strong increase = 3) Prolonged prothrombin time( 3 but 6 s = 2) Fibrinogen level(1.0g/L = 0; 1.0g/L = 1)4. Calculate scoreIf 5: compatible with overt DIC: repeat score dailyIf 5: suggestive (not affirmative) for non-overt
13、DIC: repeat next 12 days.Differential diagnosisDIC and severe liver disease DIC and TTPThe distinction between DIC and severe liver diseaseDICSevere liver diseaseMicrocirculation disturbanceEarly, commonLate, seldomJaundiceMild,seldomSevere,very commonRenal function abnormalityEarly, commonLate, sel
14、domRBC injuryCommonrareF :CNProduction of platelet activation and metabolismNFPAN/(mild)D-dimerN/(mild)The distinction between DIC and TTPDICTTPOnset and courseAbrupt,Short courseAcute/insidious,long courseMicrocirculation disturbancecommonSeldomJaundiceMild,seldomSevere,very commonF :CNProtein CNFP
15、ANF1+2ND-dimerNCharacter of thrombusFibrin thrombusPlatelet thrombusTreatmentManagement of underlying disordersintensive antibiotic treatment in patients with gram-negative bacteremia;hysterectomy in patients with abruptio placenta;resection of an aortic aneurysm;debridement of crushed tissues;chemo
16、therapy of acute leukemia;supportive care: fluids, pressors, dialysis, and respiratory and ventilator management.Heparinmechanismlysine sites active arginine serine reactive center centerThrombinantithrombin heparinTreatment: anticoagulation1.heparinIndications forms manifested by thrombosis or acro
17、cyanosis forms that accompany cancer, vascular malformations, retained dead fetus, acute promyelocytic leukemia.Treatment: anticoagulation1.heparinDosage The optimal dosage of heparin is the source of some disagreement;50u/kg, intravenous infusion, Q6h5000-10000u, subcutaneously,Q12-24h Treatment: a
18、nticoagulation1.heparinLaboratory monitoringaPTT: a prolongation of between 1.5 and 2 times normal;CT;Reversal of heparin effect1mg protamine sulfate : 100u heparininfused intravenouslyrate of infusion 5mg/minTreatment: anticoagulation1.heparinlow-molecular-weight heparin(LMWH)Treatment: anticoagula
19、tion1.heparinLMWHCharacteristicsPosses higher anti-a activity than anti-thrombin activity;Longer half-time and a higher, more reliable bioavailabilityA lower incidence of bleeding complications.Usage 75-150IUA a/Kg.d, subcutaneously, 3-5days.Treatment: anticoagulation2. othersAT-Decrease the dose of
20、 heparin;Improve the response.Dose: 1500-3000u Bid-Tid, intravenous infusion5-7days;Treatment: Antiplatelet drugsIndicationsin hypercoagulability state; the diagnosis of DIC is still not certain; in mild cases.Usage compound danshen infusion 20-40ml Bid-Tid3-5daysLow molecular weight dextran 500-100
21、0ml/d3-5days Ticlopidine(噻氯匹定噻氯匹定) 250mg Bid p.o. 5-7days Dipyridamole(双嘧达莫双嘧达莫) 500mg/d 3-5days; Treatment: Haemostatic supportplatelet concentratesplatelet count 20109/L or have severe life-threatening bleeding; fresh frozen plasma (FFP)10-15ml/kg body weight when the INR of PT is greater than 1.5
22、; cryoprecipitate1-4 unit/10kg body weight when the fibrinogen concentration is 0.8g/l or less. Fibrinogen1st dose: 2-4g (1-1.5g50mg/L)PPSB200u=200ml FFPTreatment: Fibrinolytic inhibitorsIndicationsthe underlying disorders have already controlled or cured;excessive fibrinolysis is observed;Late stag
23、e of DIC;Contraindicationspatients with early stage of DIC.Treatment: Fibrinolytic inhibitorsUsagePAMBA(氨甲苯酸氨甲苯酸)600-800mg/dtranexamic acid(氨甲环酸氨甲环酸)500-700mg/d-aminocaproic acid(氨基已酸氨基已酸)4-10g/dlAttentionThese agents should be preceded by replacement of depleted blood components and continuous hepa
24、rin infusion.Summary治疗：治疗：总结总结 DIC各期治疗原则各期治疗原则早期早期首选肝素加血小板聚集抑制药；首选肝素加血小板聚集抑制药；禁用纤溶抑制药；禁用纤溶抑制药；不需输血及补充凝血因子；不需输血及补充凝血因子；治疗：治疗：总结总结 DIC各期治疗原则各期治疗原则中期中期肝素治疗为主；肝素治疗为主；适当输血及补充凝血因子；适当输血及补充凝血因子；在应用肝素基础上慎重使用小剂量在应用肝素基础上慎重使用小剂量抗纤溶药；抗纤溶药；治疗：治疗：总结总结 DIC各期治疗原则各期治疗原则晚期晚期抗纤溶药以及输血补充凝血因子为主；抗纤溶药以及输血补充凝血因子为主；如不能确定血管内凝血是否终止可同时如不能确定血管内凝血是否终止可同时使用小剂量肝素；使用小剂量肝素；
