病理生理学（周平）复旦大学-2014 年 DIC八年制.pptxVIP

凝血与抗凝血平衡紊乱Coagulation anticoagulation disturbances向 萌Department of physiology and pathophysiologyShanghai medical schoolFudan University凝血与抗凝血的平衡抗凝血系统止血的过程抗凝血管痉挛凝血系统凝血血小板血栓形成纤溶纤维蛋白凝块形成纤溶系统COAGULATION CASCADEGeneral Features 1.Zymogens converted to enzymes by limited proteolysis2.Complex formation requiring calcium,phospholipid surface, cofactors ?3.Thrombin converts fibrinogen to fibrin monomer 4.Fibrin monomer crosslinked to fibrin forms glue for platelet plugEffect of platelets on blood coagulationThey present phospholipids on their surface that are essential for coagulation reactions.There are 4 stages for formation of the platelet plug.Platelet activation: collagen, thrombin, ADP, TXA2, PAFPlatelet adhesion: vWF, collagen, fibronectinPlatelet aggregation: collagen, thrombin, ADP, GPIIb/IIIaPlatelet secretion: ADP, Ca2+抗凝系统细胞抗凝系统 单核巨噬细胞系统对凝血因子、组织因子、凝血酶原激活物及可溶性纤维蛋白单体的吞噬、清除作用。体液抗凝系统 丝氨酸蛋白酶抑制物类 蛋白酶类 组织因子途径抑制物TFPI is synthesized by EC.Inhibit the activation of FXa and FVIIaATIII is synthesized by EC and liver cell.Inhibit the activation of FXa,FVIIa,FXIa,FIXaHeparin combines with ATIII to enhance its activity.Fibrinolytic systemPlasminogenExtrinsic activatorsenzymesPAI-1ECPro-PAt-PA, u-PAIntrinsic activatorsSecretionUrine（UK，u-PA）Bile（bilokinase）Latex、saliva、tearCoagulation PAI-3Ⅺa Tissue ⅡaⅫa Ⅻ lung、prostate、uterusBlood cellPAI-2KK RBC, PlateletExogenous activatorsVEC-HK Thrombolytic drugsStreptokinase (SK)Urokinase (UK)rt-PAPK α2-plasmin inhibitor (α2-PI)α2- macroglobin (α2 –MG)Plasmin Proteolyses fibrinogen, fibronectin , laminin ,thrombospondin；Activates collagenases.InactivateVa,VIIIaInhibit Xa, IIaPlasminTraumaAdrenalinThrombinADPTFPIPSNO, PGI2 ADPase PlasminoginActivatorst-PA, u-PAThrombinPC APC?TMAT III+HeparinAnticoagulant function of endothelial cellsInhibit platelet aggregationPrevent fibrinclot formationFibrinolysisInhibit Xa,VIIa,TF(Clinical example) 一患者因吃不洁食品，发热腹泻入院。不久患者突然发生呕血和便血，经考虑可能是溃疡出血，遂予止血药治疗，无效。患者很快出现血尿，皮肤多处紫斑，甚至从注射针眼处向外渗血，很快