Disseminated Intravascular Dic Auto Saved]

8/3/2019 Disseminated Intravascular Dic Auto Saved]

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Presented by

Chandika Dahal

Bsc.mlt 6th sem

Nobel college


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CONTENTS

y Introduction

y Causes

y Pathophysiologyy Coagulation

y Signs and symptoms(clinical features)

y Conditions

y

Diagnosisy Treatment

y Summary

y References


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INTRODUCTIONy Also known as disseminated intravascular coagulopathy or

consumptive coagulopathy.

y It is pathological activation of coagulation(blood clotting)mechanism that happens in response to a variety ofdiseases.

y It is a hemorrhagic disorder in which the diffuse

intravascular coagulation causes haemostatic defect.y DIC leads to the formation of small blood clots inside the

blood vessels throughout the body.


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An acquired syndrome characterized by the intravascularactivation of coagulation with loss of localization arising

from different causes. It can originate from and causedamage to the microvasculature, which if sufficientlysevere, can produce organ dysfunction

Taylor, FB, et al. Thromb Haemost 2001;86:1327


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DICy An acquired syndrome

characterized bysystemic intravascular

coagulationy Coagulation is always the

initial event.y Most morbidity and

mortality depends on

extent of intravascularthrombosisy Multiple causes

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ThrombosisThrombosis

FibrinFibrin

Red Blood CellRed Blood Cell

PlateletPlatelet

WWW. Coumadin.com


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DICy An acquired syndrome

characterized bysystemic

intravascularcoagulation

y Coagulation is always theinitial event

SYSTEMIC ACTIVATION

OF COAGULATION

Intravascular deposition

offibrin

Depletionofplateletsandcoagulation

factors

Thrombosisofsmalland

midsizevesselsBleeding

OrganfailureDEATHDEATH


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CAUSES

y It may be acute ,subacute or chronic.

y Cancers of lungs,pancreas,prostate,and stomach as well as

acute myeloid leukemia(particularlyAPML).y Obstetric:abruptio placentae,pre-eclampsia,amniotic fluid

embolism.

y Massive tissue injury:Trauma,burns,extensive surgery.

y Infections: Gram negative sepsis,Neisseriameningitidis,streptococcuspneumoniae,malaria,histoplasmosis,asperillosis,Rockeymountain spotted fever.


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y Miscellaneous: liver disease, snakes bites,shock,heatstroke,vasculitis,aortic aneurysm, serotonin syndrome.

yViral: Arena viruses causing Argentine hemorrhagic fever orBolivian hemorrhagic fever.


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PATHOPHYSIOLOGY

DIC may caused by:

1. Release or entry of tissue factors that act as coagulant

into the blood stream.2. Extensive endothelial damage.

Released coagulants are normally inactivated bynaturally occurring circulating inhibitors and are clearedby RE system.

The occurrence of intravascular coagulation isaugmented by the stasis which prevents the circulatinginhibitors by reaching the coagulants and by REblockade.


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Pathophysiology ofDICy Activation of Blood Coagulation

y Suppression of PhysiologicAnticoagulant Pathways

y Impaired Fibrinolysisy Cytokines


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Pathophysiology ofDICy Activation of Blood Coagulation

y Tissue factor/factor VIIa mediated thrombin generation via

the extrinsic pathwayy complex activates factor IXand X

y TF

y endothelial cells

y monocytes

y Extravascular:

y lung

y kidney

y epithelial cells


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Pathophysiology ofDICy Suppression of PhysiologicAnticoagulant Pathways

y reduced antithrombin III levels

y reduced activity of the protein C-protein S systemy Insufficient regulation of tissue factor activity by tissue factor

pathway inhibitor (TFPI)

y inhibits TF/FVIIa/Fxa complex activity


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Pathophysiology ofDICy Impaired Fibrinolysis

y relatively suppressed at time of maximal activation of

coagulation due to increased plasminogen activatorinhibitor type 1


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Coagulationy Intrinsic Pathwayy Extrinsic Pathwayy Common Pathwayy Contact Pathwayy

Tissue Factor Pathwayy Primary factor in DIC

5

Contact Tissue Factor + VIITissue Factor + VII

XIIIXIIIaa

XIIIXIII

ThrombinThrombin

FibrinFibrin(strong)(strong)

FibrinogenFibrinogen FibrinFibrin(weak)(weak)

IXIX

XIXI

XIXIaa

IXIXaa

XXaaVVaa

XIIXIIaa

ProthrombinProthrombin

TF-VIITF-VIIaa

(Prothrombinase)(Prothrombinase)

PLPL

PLPL

(Tenase)(Tenase)

VIIIVIIIaa

PLPL

XX

Intrinsic Pathway

HKHKaa

Extrinsic Pathway

Common Pathway

TF Pathway

Coagulation PathwaysCoagulation Pathways

Protein C, ProteinS, Antithrombin III

Www.coumadin.com


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Anticlotting Mechanismsy Antithrombin III (ATIII):

y The major inhibitor of thecoagulation cascade.

y Inhibits Thrombiny Inhibits activated Factors IX, X,

XI, and XII.

y Activity is enhanced by heparin.

y Tissue factor pathway inhibitorTFPI

5


XIIIXIIIaa

XIIIXIII

ThrombinThrombin



IXIX

XIXI

XIXIaa

IXIXaa

XXaaVVaa

XIIXIIaa


TF-VIITF-VIIaa


PLPL

PLPL

(Tenase)(Tenase)

VIIIVIIIaa

PLPL

XX

Intrinsic Pathway

HKHKaa

Extrinsic Pathway

Common Pathway

TF Pathway


Protein C, Protein

S, Antithrombin III

Www.coumadin.com


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Anticlotting Mechanismsy Protein C

y Activated byThrombin/Thrombomodulin

y Anticoagulant and fibrinolyticactivity.

y Vitamin K and Protein S arecofactors

y Protein S

5


XIIIXIIIaa

XIIIXIII

ThrombinThrombin



IXIX

XIXI

XIXIaa

IXIXaa

XXaaVVaa

XIIXIIaa


TF-VIITF-VIIaa


PLPL

PLPL

(Tenase)(Tenase)

VIIIVIIIaa

PLPL

XX

Intrinsic Pathway

HKHKaa

Extrinsic Pathway

Common Pathway

TF Pathway


Protein C, ProteinS, Antithrombin III

Www.coumadin.com


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Fibrinolytic Systemy Plasmin

y Produced fromPlasminogen by Tissue

Plasminogen activator(TPA)

y Degrades Fibrin andFibrinogen (Fibrindegradation products,

FDP)y Degrades Factors V, VIII,IX, XI, and XII.

y Activity is inhibited byAntiplasmin.

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FibrinolysisFibrinolysisPlasminogen

Plasmin

Fibrin, fibrinogenFibrin, fibrinogen

ActivationActivation

Extrinsic: t-PA,Extrinsic: t-PA, urokinaseurokinase

Intrinsic: factor XIIa, HMWK,Intrinsic: factor XIIa, HMWK, kallikreinkallikrein

Exogenous:Exogenous: streptokinasestreptokinase


degradation productsdegradation products

Www.coumadin.com


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Fibrinolytic Inhibitorsy Antiplasmin

y Inactivates plasmin rapidly.

y Acts slowly on plasminsequestered in the fibrin

clot.

y Inactivates factors XI and XIIslowly.

y Plasminogen -ActivatorI

nhibitor-1(PAI

-1)y Inhibits the function of TPAy Also has some inhibitory

activity against urokinase,plasmin, thrombin, activatedProtein C, factors and XII, and

kallikrein

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FibrinolysisF

ibrinolysisPlasminogen

Plasmin


ActivationActivation

Extrinsic: t-PA,Extrinsic: t-PA, urokinaseurokinase

Intrinsic: factor XIIa, HMWK,Intrinsic: factor XIIa, HMWK, kallikreinkallikrein

Exogenous:Exogenous: streptokinasestreptokinase

Fibrin, fibrinogenFibrin, fibrinogendegradation productsdegradation products

Www.coumadin.com


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CLINICALFEATURES

Two main clinical features of DIC

1.Bleeding

2.Organ damage


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Clinical Manifestations ofDICORGAN ISCHEMIC HEMOR.

Skin Pur. FulminansGangrene

Acral cyanosis

Petechiae

Echymosis

OozingCNS Delirium/Coma

Infarcts

Intracranial

bleeding

Renal Oliguria/AzotemiaCortical Necrosis

Hematuria

Cardiovascular MyocardialDysfxn

Pulmonary Dyspnea/HypoxiaInfarct

Hemorrhagiclung

GI

Endocrine

Ulcers, Infarcts

Adrenal infarcts

Massive

hemorrhage.

Ischemic Findingsareearliest!

Bleedingisthemos obviousclinicalfinding


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Clinical Manifestations ofDIC


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Conditions Associated With DICy Malignancy

y Leukemia

y Metastatic diseasey Cardiovascular

y Post cardiac arrest

y Acute MI

y Prosthetic devicesy Hypothermia/Hyperthermi

a

y Pulmonary

y ARDS/RDS

y Pulmonary embolismy Severe acidosis

y Severe anoxia

y Collagen vascular disease

y Anaphylaxis


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Conditions Associated With DICy Infectious/Septicemia

y Bacterialy

Gm - / Gm +y Viral

y CMV

y Varicella

y Hepatitis

y Fungal

y Intravascular hemolysis

y Acute Liver Disease

y Tissue Injuryy trauma

y

extensive surgeryy tissue necrosis

y head trauma

y Obstetricy Amniotic fluid emboli

y Placental abruption

y Eclampsia

y Missed abortion


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Microscopic findings in DIC

y Fragments

y Schistocytesy Paucity of platelets


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Laboratory diagnosisy Thrombocytopeniay plat count


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Differential Diagnosisy Severe liver failure

yVitamin K deficiency

y Liver diseasey Thrombotic thrombocytopenic purpura

y Congenital abnormalities of fibrinogen

y HELLP syndrome


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Laboratory Tests Used in DICy D-dimer*

y Antithrombin III*

y F. 1+2*y FibrinopeptideA*

y Platelet factor 4*

y Fibrin Degradation Prod

y Platelet count

y Protamine test

y Thrombin time

y Fibrinogen

y Prothrombin timey Activated PTT

y Protamine test

y Reptilase time

y Coagulation factor levels

*Most reliable test


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Treatment ofDICy Stopthetriggeringprocess .

y The only proven treatment!

y Supportive therapyy No specific treatments

y Plasma and platelet substitution therapy

y Anticoagulants

y Physiologic coagulation inhibitors


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Plasma therapyy Indications

y Active bleeding

y Patient requiring invasive procedures

y Patient at high risk for bleeding complications

y Prophylactic therapy has no proven benefit.

y Cons:

y Fresh frozen plasma(FFP):y provides clotting factors, fibrinogen, inhibitors, and platelets in

balanced amounts.y Usual dose is 10-15 ml/kg


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Platelet therapyy Indications

y Active bleeding

y Patient requiring invasive proceduresy Patient at high risk for bleeding complications

y Platelets

y approximate dose 1 unit/10kg


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Bloody Replaced as needed to maintain adequate oxygen delivery.

y Blood loss due to bleeding

y

RBC destruction (hemolysis)


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Summaryy DIC is a syndrome characterized systemic intravascular

coagulation.

y

Coagulation is the initial event and the extent of intravascularthrombosis has the greatest impact on morbidity and mortality.

y Important link between inflammation and coagulation.

y Morbidity and mortality remain high.

y The only proven treatment is reversal or control of the

underlying cause.


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REFERENCES

y De Gruchys Clinical haematology in medical practice 5th

edu.

y

www.coumdin.com.y Teachers note.


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y

THA

NK YOU

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