Disseminated Intravascular Coagulation

Introduction of DIC

An An acquiredacquired syndrome syndrome characterized by characterized by systemicsystemic intravascular coagulation intravascular coagulation and and secondary bleedingsecondary bleeding

Coagulation Coagulation is is alwaysalways the initial the initial event.event.

Morbidity: 0.2‰-0.5 ‰ Mortality: Morbidity: 0.2‰-0.5 ‰ Mortality: 50%-60%50%-60%

Multiple causesMultiple causes

Hemostasis Review

Coagulation cascadeCoagulation cascade Vascular EndotheliumVascular Endothelium Anticlotting Anticlotting

MechanismsMechanisms Fibrinolytic SystemFibrinolytic System Blood Flow DynamicsBlood Flow Dynamics

3

HemostasisHemostasisSubendothelialSubendothelial matrix matrix

PlateletsPlatelets

HemostaticHemostatic plug plug

FibrinFibrin

Endothelial cellEndothelial cell

RBCRBCWBCWBC

WBCWBC

1.Coagulation Intrinsic PathwayIntrinsic Pathway Extrinsic PathwayExtrinsic Pathway Common PathwayCommon Pathway Contact PathwayContact Pathway Tissue Factor PathwayTissue Factor Pathway

Primary factor in DICPrimary factor in DIC

5

Contact Tissue Factor + VIITissue Factor + VII

XIIIXIIIaa

XIIIXIII

ThrombinThrombin

FibrinFibrin(strong)(strong)

FibrinogenFibrinogen FibrinFibrinmonomermonomer

IXIX

XIXI

XIXIaa

IXIXaa

XXaaVVaa

XIIXIIaa

ProthrombinProthrombin

TFTF--VIIVIIaa

(Prothrombinase)(Prothrombinase)

PLPL

PLPL(Tenase)(Tenase)

VIIIVIIIaa

PLPL

XX

Intrinsic Pathway

HKHKaa

Extrinsic Pathway

Common Pathway

TF Pathway

Coagulation PathwaysCoagulation Pathways

TF is a transmembrane glycoprotein which contains TF is a transmembrane glycoprotein which contains abundant phosphatide.abundant phosphatide.

When TF enters blood, the calcium ions combine F ⅦWhen TF enters blood, the calcium ions combine F Ⅶto the phosphatide of TF to form a complex which can to the phosphatide of TF to form a complex which can activate F to F a.Ⅹ Ⅹactivate F to F a.Ⅹ Ⅹ

F a , calcium , F a and phosphatide of PL act together Ⅹ ⅤF a , calcium , F a and phosphatide of PL act together Ⅹ Ⅴto produce an activator of prothrombin. Finally to produce an activator of prothrombin. Finally thrombin can be produced. thrombin can be produced.

VEC is not express TF in normal state. But endotoxin VEC is not express TF in normal state. But endotoxin stimulation of VEC also produces TF.stimulation of VEC also produces TF.

Normal tissues and malignant tumors contain a large Normal tissues and malignant tumors contain a large amount of TF. Different tissue contain different amount of TF. Different tissue contain different amount of TF amount of TF

Tissue Factor Tissue Factor （（ TFTF））

Activity of TFActivity of TF

tissue Activity of TFtissue Activity of TF （（ //mgmg ）） Liver 10 Liver 10 Muscle 20Muscle 20 brain 50brain 50 Lung 50Lung 50 PlacentaPlacenta 2000 2000

2.Vascular Endothelium

Vascular endothelium expressesVascular endothelium expresses: : Tissue Plasminogen Activator (t-pA)Tissue Plasminogen Activator (t-pA) ， ， t-PAIt-PAI Tissue factor pathway inhibitor (TFPI)Tissue factor pathway inhibitor (TFPI) Tissue factor (TF)Tissue factor (TF) NONO ，， PGIPGI2 2 / ET/ ET

Thrombomodulin (TM, Thrombomodulin (TM, 凝血酶调节素凝血酶调节素▽▽ ):):

Activated PC（ APC ）

Inactivates aⅤ Ⅷ、 a;

Inhibits a Ⅹbinding to PL; Leads to release of t-PA

thrombomodulin (TM)

Surface of VEC

thrombin

prothrombincoagulation activity

Protein S

thrombomodulin (TM ): A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation.

Protein C, PC

3.Anticlotting Mechanisms

1) Antithrombin III (A-TIII): 1) Antithrombin III (A-TIII): The major inhibitor of the coagulation The major inhibitor of the coagulation

cascade.cascade. Inhibits Thrombin (70%-80%)Inhibits Thrombin (70%-80%) Inhibits activated Factors IX, X, XI, Inhibits activated Factors IX, X, XI,

and XII.and XII. Activity is enhanced by heparin.Activity is enhanced by heparin. Produced mainly by liverProduced mainly by liver

2) Tissue factor pathway inhibitor 2) Tissue factor pathway inhibitor

（（ TFPITFPI ）） : a, Xa Ⅶ: a, Xa Ⅶ

Produced by ECProduced by EC 3) Protein C sytem: VEC (3) Protein C sytem: VEC ( a, a, aⅤ Ⅷ Ⅹ ) )

4. The fibrinolytic system

Plasminogen

Plasmin

Fibrin, fibrinogenFibrin, fibrinogen

Tissue Plasminogen Activator (t-PA)Tissue Plasminogen Activator (t-PA)Urokinase (uPA)Urokinase (uPA)

Thrombin, F a, F aⅫ ⅪThrombin, F a, F aⅫ Ⅺ

Fibrin/ fibrinogen degradationFibrin/ fibrinogen degradationproducts (FgDP / FDPproducts (FgDP / FDP▽▽))

Plasmin Inhibitor

PAI-1

FgDP/ FDP 概念：概念： 纤维蛋白（原）降解纤维蛋白（原）降解

产物，指纤维蛋白（产物，指纤维蛋白（原）被纤溶酶分解后原）被纤溶酶分解后形成的多肽碎片形成的多肽碎片

作用：作用： 1 1 抑制纤维蛋白单体聚合抑制纤维蛋白单体聚合 2 2 抗凝血酶抗凝血酶 3 3 抑制抑制 PltPlt 粘附、聚集、释粘附、聚集、释

放放

5. Phagocytosis of mononuclear phagocyte system 5. Phagocytosis of mononuclear phagocyte system (MPS):(MPS):

Most of the products of intravascular coagulation Most of the products of intravascular coagulation (fibrin monomer, prothrombin etc.), as well as (fibrin monomer, prothrombin etc.), as well as various initiators of the process (endotoxin, tissue various initiators of the process (endotoxin, tissue fragments, antigen-antibody complexes etc.) are fragments, antigen-antibody complexes etc.) are removed from the circulation by MPS through removed from the circulation by MPS through unselective phagocytosis.unselective phagocytosis.

coagulation anticoagulation

1.Intrinsic coagulation pathway（Ⅻ→ Ⅻ a ）2.Extrinsic coagulation pathway （ TF enters into blood ）

1. Intact VEC

2.quite rapid blood flow velocity 3. Phagocytosis of MPS

4.physiological anticoagulation substances: AT-Ⅲ、 PC 、 TFPI

5. Fibrinolytic system

summary

The Concept of DICThe Concept of DIC The Causes and The Causes and Accelerating Accelerating factors of DICfactors of DIC The Pathophysiology of DICThe Pathophysiology of DIC Clinical Manifestations of DICClinical Manifestations of DIC The Stages and Types of DICThe Stages and Types of DIC The Diagnosis and Treatment of DCThe Diagnosis and Treatment of DC

一 .Concept of DIC

DIC 是一种继发性的、以广泛微血栓形成并相继出现止、凝血功能障碍为病理特征的临床综合征。

SYSTEMIC ACTIVATION OF COAGULATION

Intravascular deposition of

fibrin

Depletion of platelets and coagulation

factors

Thrombosis of small and midsize

vesselsBleeding

Organ failure DEATHDEATH

二、 Causes and accelerating factors factors of DIC

1.1. The causes and triggering factors of DICThe causes and triggering factors of DIC

CausesCauses ：引起：引起 DICDIC 的基础疾病或病理过程（病因性的基础疾病或病理过程（病因性疾病）疾病）

Common Causes of DIC

感染性疾病 : 细菌感染败血症、内毒素血症、病毒性肝炎、流行性出血热

广泛组织损伤 : 大面积挫伤或烧伤、挤压综合症、大手术、器官移植

产科意外 : 胎盘早剥、羊水栓塞、宫内死胎、妊娠中毒症、流产术

恶性肿瘤 : 肺、消化系及泌尿系癌、转移癌、恶性葡萄胎、绒毛膜上皮癌

急性白血病 : 急性早幼粒白血病

其他疾病 : 内毒素休克、严重出血或过敏性休克、大面积心肌梗死、异型输血、巨大海棉状血管瘤、肾小球肾炎、类风湿关节炎、系统性红斑狼疮、肾移植排斥反应

Triggering factors of DIC

Tissue injury: Tissue injury: TF enters into bloodTF enters into blood VEC injury:VEC injury: EndotoxinEndotoxin Ag-Ab complexAg-Ab complex ProteaseProtease Others:particles, virus, hypoxiaOthers:particles, virus, hypoxia

2. Precipitating factor (accelerating factors ) of DIC

（（ 1) 1) Impairment of Impairment of the MPSthe MPS

（（ 22 ） ） Liver DiseaseLiver Disease

（（ 33 ） ） Hypercoagulable state of bloodHypercoagulable state of blood

（（ 44 ） ） Microcirculation dysfunctionMicrocirculation dysfunction

（（ 55 ） ） OthersOthers

(1)Impairment of the mononuclear phagocyte system The mononuclear phagocyte system (MPS) The mononuclear phagocyte system (MPS) is is

composed of composed of mononuclear cell and phagocyte.mononuclear cell and phagocyte. Most of the products of intravascular coagulation Most of the products of intravascular coagulation

(free fibrin, prothrombin activator), as well as (free fibrin, prothrombin activator), as well as various initiators of the process (endotoxin, tissue various initiators of the process (endotoxin, tissue fragments, antigen-antibody complex, fragments, antigen-antibody complex, thromboplastins) are removed from the circulation thromboplastins) are removed from the circulation by the unspecific phagocytosis of MPSby the unspecific phagocytosis of MPS

Kupffer cell in liver are very important in the Kupffer cell in liver are very important in the clearance of activated clotting factors ( a, a Ⅸ Ⅹclearance of activated clotting factors ( a, a Ⅸ Ⅹand a)Ⅻand a)Ⅻ

Any factors that decrease or impair MPS will Any factors that decrease or impair MPS will accelerate the occurrence of DIC in a manner accelerate the occurrence of DIC in a manner comparable to that produced experimentally in comparable to that produced experimentally in the general Shwarzman reaction (GSR) in the general Shwarzman reaction (GSR) in animalsanimals

Generalized Shwartzman reaction （ GSR ）

1924, Sanarelli: 1924, Sanarelli:

亚致死量霍乱菌滤液亚致死量霍乱菌滤液 i.v. i.v. RatRat 24h24h i.v. i.v. 大肠杆菌或变形杆菌大肠杆菌或变形杆菌滤液滤液 RatRat died of died of shockshock

DIC and shockDIC and shock

haemorrhagic infarcthaemorrhagic infarct

Mechanism:Mechanism:

长期大量应用糖皮质激素长期大量应用糖皮质激素 ,, 反复感染或严重肝反复感染或严重肝疾病 疾病 ↓↓ the function of MPS the function of MPS ↑DIC↑DIC

(2) Severe Liver Disease Some causes (Ag-Ab complex, drugs) of the disease may Some causes (Ag-Ab complex, drugs) of the disease may

directly activate coagulationdirectly activate coagulation Acute severe hepatitis release TF and Acute severe hepatitis release TF and lysosome enzymelysosome enzyme; there ; there

is is gutdrived endotoxemia at the gutdrived endotoxemia at the late stage of hepatocirrhosis late stage of hepatocirrhosis Impaired synthesis of some clotting factors such as FII, FVII, Impaired synthesis of some clotting factors such as FII, FVII,

FV, FIX and FX also Antithrombin ,Proteins C (PC) and S FV, FIX and FX also Antithrombin ,Proteins C (PC) and S (PS)(PS)

Impaired synthesis anti-clotting factors such as of PC, PS and Impaired synthesis anti-clotting factors such as of PC, PS and antithrombin can lead to susceptibility to DICantithrombin can lead to susceptibility to DIC

The damaged liver reduces the clearance of activated clotting The damaged liver reduces the clearance of activated clotting factors such as F a and F a.Ⅹ Ⅱfactors such as F a and F a.Ⅹ Ⅱ

Often associated with bleedingOften associated with bleeding

(3) Hypercoagulable state of blood

Primary: Primary: inherited lack of AT- , PC and PS Ⅲinherited lack of AT- , PC and PS Ⅲor PC-resisting syndrome or PC-resisting syndrome

Secondary: Secondary:

1) Pregnancy: the blood in pregnancy after 3 months begins to increase the blood in pregnancy after 3 months begins to increase

coagulability, which is most marked in the terminal stage of coagulability, which is most marked in the terminal stage of pregnancypregnancy

a) PL and clotting factors (F , F ,F , F , F , F , F ) are Ⅰ Ⅱ Ⅴ Ⅶ Ⅸ Ⅹ Ⅻa) PL and clotting factors (F , F ,F , F , F , F , F ) are Ⅰ Ⅱ Ⅴ Ⅶ Ⅸ Ⅹ Ⅻincreasedincreased

b) the substances with the action of anticoagulation (AT- ) and Ⅲb) the substances with the action of anticoagulation (AT- ) and Ⅲwith the activity of fibrinolysis (t-PA, u-PA)are decreasedwith the activity of fibrinolysis (t-PA, u-PA)are decreased

c) fibrinolysis inhibitors are increasedc) fibrinolysis inhibitors are increased

→ → form the hypercoagulable state of blood in pregnancyform the hypercoagulable state of blood in pregnancy Therefore, Therefore, obstetrical suddenness (such as amniotic fluid embolism, obstetrical suddenness (such as amniotic fluid embolism,

early separation of placenta, died fetus) is very easy to induce early separation of placenta, died fetus) is very easy to induce DIC DIC

2) Acidosis: acidosis causes the reducing of pH of the blood →

a) VEC can be damaged by increased [Ha) VEC can be damaged by increased [H++]] d) The activity of heparin is decreased.d) The activity of heparin is decreased. c) activity of clotting factors and platelets is c) activity of clotting factors and platelets is

increasedincreased d) disturbance the vessel movement activity and d) disturbance the vessel movement activity and

hemorheology:↑vessel permeability, blood hemorheology:↑vessel permeability, blood oozing oozing , , → high blood viscosity, → high blood viscosity,

vasodilation, slow blood flow vasodilation, slow blood flow velocity.velocity.

→ → hypercoagulable state of bloodhypercoagulable state of blood

Vessel’s movement and reaction↓ disorders of hemorheologyVEC was damagedTissue was damagedInflammation and inflammatory mediaMultiple Organs dysfunction → formation of DIC

(4)Microcirculation dysfunctionLocal: vessel movement, blood, acidosis, VEC, WBC

Systemic: shock→

(5) Others

Old age, smoking, late stage of pregnancy, diabetes , Old age, smoking, late stage of pregnancy, diabetes , unapt using of unapt using of inhibitorinhibitor →→decreased activity of decreased activity of

fibrinolysisfibrinolysis systemsystem

stress → impaired movement of vessel

Experiment: alive animalEndotoxin or thrombin i.v. →microthrombosis is temporal, about 1hPlus fibrinolytic inhibitor or NE → the reservation of microthrombosis

三、 Pathophysiology of DIC

Activation of Blood CoagulationActivation of Blood Coagulation The changes of vessel’s movement and The changes of vessel’s movement and

hemodynamics hemodynamics （血液动力学）（血液动力学） Impaired FibrinolysisImpaired Fibrinolysis

The course of DIC occurrence :To trigger coagulation →the deposit and reserve of Fbn

（一） Activation of Blood Coagulation

11 、、 Tissue injuryTissue injury 22 、、 VEC injuryVEC injury 33 、、 Other pathwaysOther pathways

causescauses ：： sever trauma, burn, major operation, sever trauma, burn, major operation, malignant necrosismalignant necrosis

mechanismmechanism ：： tissue factor enters into bloodtissue factor enters into blood

lysosome enzyme lysosome enzyme (may activate clotting factors)(may activate clotting factors)

1.Severe tissue injury →to activate extrinsic 1.Severe tissue injury →to activate extrinsic coagulation systemcoagulation system

2. Extensive damage of VEC→loss of balance between coagulation and anticoagulation

causescauses ：： infection, hypoxia, acidosis,infection, hypoxia, acidosis, antigen-antibody complex Fbnantigen-antibody complex Fbn

Mechanism:Mechanism: Damaged Damaged VEC (micro-V. and Capi) express TFVEC (micro-V. and Capi) express TF →→ to to trigger trigger

extrinsic coagulation systemextrinsic coagulation system VEC was damaged→blood contacts with exposed collagen to VEC was damaged→blood contacts with exposed collagen to

activate F to form F a → intrinsic clotting cascade is Ⅻ Ⅻactivate F to form F a → intrinsic clotting cascade is Ⅻ Ⅻtriggered. triggered.

WBC :TNF, IL-1, PAF, superoxide, C3a C5a →↑the injury of WBC :TNF, IL-1, PAF, superoxide, C3a C5a →↑the injury of VECVEC

Anticoagulation and fibrinolysis activity are decreased:Anticoagulation and fibrinolysis activity are decreased:

anticoagulants(TFPI , TM, AT- ) ↓, PAI↑ Ⅲanticoagulants(TFPI , TM, AT- ) ↓, PAI↑ Ⅲ ET ↑, / NO ↓, PGIET ↑, / NO ↓, PGI22 ↓ ↓

Platelet activation.Platelet activation.

PL adhesion to damaged VECNomal VEC （ scanning electron microscope ）

3. Other pathways to induce coagulation

Activated mononuclear phagocyteActivated mononuclear phagocyte ：： TF, TF, lysosome lysosome enzymeenzyme

Malignant tumors:TF,Malignant tumors:TF, cancer procoagulantcancer procoagulant （★（★ F ) ⅩF ) Ⅹ Trypsin Trypsin (( 胰蛋白酶胰蛋白酶 ): hemorrhagic acute pancreatitis, ): hemorrhagic acute pancreatitis,

pancreas malignant tumor→ Trypsin → pancreas malignant tumor→ Trypsin → ★★FⅡFⅡ Exogenous toxin Exogenous toxin ：： snake venom , bee venomsnake venom , bee venom → → ★★F , F , FⅩ Ⅱ ⅠF , F , FⅩ Ⅱ Ⅰ Severe haemolysisSevere haemolysis: : ADP ADP （★（★ PL), PL), 红细胞素具红细胞素具 TFTF 样作用 样作用

( 二 ) The changes of vessel’s movement and hemodynamics sympatho-adrenomedullary system (SAS)sympatho-adrenomedullary system (SAS) Damaged VEC: NO↓, PGIDamaged VEC: NO↓, PGI22↓/ ET ↑ ↓/ ET ↑

activated platelet:TXAactivated platelet:TXA22↑↑

PAF, histamine, Bradykinin→ ↑ capillary PAF, histamine, Bradykinin→ ↑ capillary permeability →blood viscosity ↑permeability →blood viscosity ↑

( 三 ) Impaired Fibrinolysis

11 、、 Decreased fibriolysis:Decreased fibriolysis: Damaged VEC: negative charge ↓, Damaged VEC: negative charge ↓, the expression and absorbing of TFPI↓, AT- ↓, Ⅲthe expression and absorbing of TFPI↓, AT- ↓, Ⅲ TM↓, t-PA↓, PAI-1↑TM↓, t-PA↓, PAI-1↑ 22 、、 Secondary increased fibriolysis:Secondary increased fibriolysis: coagulation→ F aⅡcoagulation→ F aⅡ Fbn →VEC release t-PAFbn →VEC release t-PA the activation of fibriolysis → FgDP/ FDP: ↑anticlottingthe activation of fibriolysis → FgDP/ FDP: ↑anticlotting → →bleedingbleeding

四、 Clinical Manifestations of DIC

BleedingBleeding ShockShock MODSMODS Microangiopathic hemolytic anemiaMicroangiopathic hemolytic anemia

1 、 bleeding ： is the most obvious clinical finding, is seen in 70~80% of DIC case, is life threatening.

Mechanism of bleeding in DICMechanism of bleeding in DIC (1) Consumption of coagulative factors ((1) Consumption of coagulative factors ( Ⅰ Ⅰ 、、ⅡⅡ、、ⅤⅤ、、ⅧⅧ 、、ⅩⅩ ) and platelet) and platelet

(2) Secondary activation of fibrinolysis system:(2) Secondary activation of fibrinolysis system:

plasminogen → plasmin:plasminogen → plasmin:

fibrin fibrin 、 、 fibrinogenfibrinogen FDPFDP Ⅱ Ⅱaa 、、ⅤⅤ、、ⅧⅧ 、、ⅫⅫ a consumptiona consumption

(3) Formation of FDP→ anticoagulation (3) Formation of FDP→ anticoagulation fibrinogenfibrinogen plasmin plasmin XX 、、 AA 、、 BB

YY 、、 D FgDP/FDPD FgDP/FDP DD 、、 EE

fibrinfibrin plasminplasmin X′X′ 、、 Y′Y′ 、、 DD 、、 E′E′

XX 、、 YY 、、 DD ：： inhibit fibrin monomer aggregationinhibit fibrin monomer aggregationYY 、、 EE ：： have anti-thrombin actionhave anti-thrombin actionMost of themMost of them ： ： inhibit platelet aggregation and releaseinhibit platelet aggregation and release

Water-solubleSmall peptide

(4) (4) Vessel was damaged:Vessel was damaged: primary factorsprimary factors secondary factors: hypoxia, acidosis, secondary factors: hypoxia, acidosis,

free radicalfree radical

2. Microcirculation disturbance -shock2. Microcirculation disturbance -shock(1) microthrombi → the blood return ↓(1) microthrombi → the blood return ↓(2) excess bleeding → blood volume ↓(2) excess bleeding → blood volume ↓(3) Cardiac output ↓:heart or lung thrombi, acidosis(3) Cardiac output ↓:heart or lung thrombi, acidosis(4) Vasodilation and permeability of capillary↑ (4) Vasodilation and permeability of capillary↑ (a) activation of complement and kinin system→histamine, kinin (a) activation of complement and kinin system→histamine, kinin

releaserelease

peripheral resistance ↓ peripheral resistance ↓ permeability of capillary ↑ permeability of capillary ↑

A,B,C → ↑ histamine, kininA,B,C → ↑ histamine, kinin (b)FDP (b)FDP vasodilationvasodilation permeability of capillary ↑permeability of capillary ↑

(1) (1) primary disease primary disease →cause organ dysfunction→cause organ dysfunction

(2) extensive microthrombi in organs →(2) extensive microthrombi in organs →

serious ischemic tissue damage serious ischemic tissue damage

(3) interaction between organs :(3) interaction between organs :

e.g. pulmonary infection →DIC, pulm. dysfunction e.g. pulmonary infection →DIC, pulm. dysfunction

→ → PaO2PaO2↓↓, PaCO, PaCO22↑↑

pulmonary artery pressure ↑ → heart dysfunctionpulmonary artery pressure ↑ → heart dysfunction

→→aggravate microcirculation disturbanceaggravate microcirculation disturbance

3. Multiple organ dysfunction syndrome (MODS)

4. microangiopathic hemolytic

anemia ( 微血管病性溶血性贫血 )

Microscopic findings in DIC

FragmentsFragments Schistocytes Schistocytes （裂体细胞）（裂体细胞） Paucity of plateletsPaucity of platelets

RBC hanging on fibrin strands （ scan electron microscope ， left2000 ， right5200 ）

五、 The Stages and Types of DIC11 、 、 Stages of DICStages of DIC

1.Hypercoagulable stage: clotting system is activated, 1.Hypercoagulable stage: clotting system is activated, thrombin in blood, microthrombithrombin in blood, microthrombi

2.Hypocoagulable stage: clotting factors and PL↓,2.Hypocoagulable stage: clotting factors and PL↓, bleedingbleeding3.Secondary fibrinolytic stage3.Secondary fibrinolytic stage FgDP/FDP→inhibit PL aggregation and fibrin formation FgDP/FDP→inhibit PL aggregation and fibrin formation

→ bleeding↑, shock ,MODS→ bleeding↑, shock ,MODS

2 、 types of DIC

六、 Diagnosis and Treatment of DIC

1. Diagnosis of DIC

Presence of disease associated with DICPresence of disease associated with DIC Appropriate clinical settingAppropriate clinical setting

Clinical evidence of thrombosis, hemorrhage or both.Clinical evidence of thrombosis, hemorrhage or both. Laboratory studiesLaboratory studies

no single test is accurateno single test is accurate serial test are more helpful than single testserial test are more helpful than single test

Conditions Associated With DIC

MalignancyMalignancy LeukemiaLeukemia

CardiovascularCardiovascular cardiac arrestcardiac arrest Acute MIAcute MI

Hypothermia/HyperthermiaHypothermia/Hyperthermia

PulmonaryPulmonary ARDSARDS Pulmonary embolismPulmonary embolism

Severe acidosisSevere acidosis Severe anoxiaSevere anoxia AnaphylaxisAnaphylaxis

Conditions Associated With DIC

Infectious/SepticemiaInfectious/Septicemia BacterialBacterial

Gm - / Gm +Gm - / Gm +

ViralViral HepatitisHepatitis

FungalFungal

Intravascular hemolysisIntravascular hemolysis Acute Liver DiseaseAcute Liver Disease

Tissue InjuryTissue Injury traumatrauma extensive surgeryextensive surgery tissue necrosistissue necrosis head traumahead trauma

ObstetricObstetric Amniotic fluid emboliAmniotic fluid emboli Placental abruptionPlacental abruption died fetusdied fetus

Clinical Manifestations of DICORGAN ISCHEMI

C HEMOR.

Skin Gangrene Acral cyanosis

Petechiae Oozing

CNS Delirium/Coma Infarcts

Intracranial bleeding

Renal Oliguria/Azotemia

Hematuria

Cardiovascular

Cardial Dysfunction

Pulmonary

Dyspnea/Hypoxia Infarct

Hemorrhagic lung

GI

Ulcers, Infarcts

Massive hemorrhage.

Ischemic Findingsare earliest!

Bleeding is the most obvious

clinical finding

2. Treatment of DIC2. Treatment of DIC

1) 1) 早期诊断和早期治疗早期诊断和早期治疗 2) 2) 积极防治原发病积极防治原发病 3) 3) 抗凝治疗抗凝治疗 , , 补充支持疗法补充支持疗法 , , 抗纤溶疗抗纤溶疗法法 4) 4) 脏器功能的维持和保护脏器功能的维持和保护

Summary

DIC is an DIC is an acquiredacquired syndrome characterized syndrome characterized systemic systemic intravascular coagulation.intravascular coagulation.

Coagulation is the initial event. Coagulation is the initial event. TF entering into bloodTF entering into blood is is primary triggering factor of coagulation. primary triggering factor of coagulation.

BleedingBleeding is the most common clinical manifestation due is the most common clinical manifestation due to the consumption (of coagulation factors and platelet) to the consumption (of coagulation factors and platelet) and secondary activation of and secondary activation of fibrinolyticfibrinolytic systemsystem

Morbidity and mortality remain high.Morbidity and mortality remain high.

The Concept of DICThe Concept of DIC The Causes and Influencing factors of DICThe Causes and Influencing factors of DIC The Pathophysiology of DICThe Pathophysiology of DIC Clinical Manifestations of DICClinical Manifestations of DIC The Stages and Types of DICThe Stages and Types of DIC The Diagnosis and Treatment of DCThe Diagnosis and Treatment of DC

典型病例 患者，女， 29 岁。因胎盘早期剥离急诊入院。 妊娠 8 个多月，昏迷，牙关紧闭，手足强直；眼球结膜有出血斑，身体多处有瘀点、瘀斑，消化道出血，血尿；血压 50/80mmHg ，脉搏 95 次 / 分、细数；尿少。 实验室检查（括号内是正常值）： Hb70g/L （ 110~150 ），RBC2.71012/L （ 3.5~5.0 12/L ），外周血见裂体细胞；血小板 85 109/L （ 100~300 109/L ），纤维蛋白原1.78g/L （ 2~4g/L ）；凝血酶原时间 20.9 秒（ 12~14 ），鱼精蛋白副凝试验（ 3P 试验）阳性（阴性）。尿蛋白 +++ ， RBC++ 。 4h 后复查血小板 75 109/L ，纤维蛋白原 1.6g/L 。 试分析该病例 DIC的 证据、发病机制、诱发因素和分期。