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Disseminated Intravascular

Coagulation

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DIC

An acquired

syndrome

characterized bysystemic

intravascular

coagulation

ThrombosisThrombosis

FibrinFibrin

Red Blood CRed Blood C

PlateletPlatelet

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Hemostasis Review

Coagulation cascade

Vascular Endothelium

Anticlotting Mechanisms

Fibrinolytic System Platelets

Blood Flow Dynamics

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Vascular Endothelium

Vascular endothelium

expresses: Thrombomodulin

Tissue PlasminogenActivator

Tissue

thromboplastin/Tissue

factor

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Coagulation

Intrinsic Pathway

Extrinsic Pathway

Common Pathway

Contact Pathway

Tissue Factor Pathway

Primary factor in DIC

Contact Tissue Factor + VIITissue Factor + VII

XIIIXIIIaa

XIIIXIII

ThrombinThrombin

FiFi(st(st

FibrinogenFibrinogen FibrinFibrin(weak)(weak)

IXIX

XIXI

XIXIaa

IXIXaa

XXaaVVaa

XIIXIIaaProthrombinProthrombin

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, Protein

S, Antithrombin III

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Anticlotting Mechanisms

Antithrombin III (ATIII): The major inhibitor of the

coagulation cascade.

Inhibits Thrombin

Inhibits activated Factors

IX, X, XI, and XII.

Activity is enhanced by

heparin.

Tissue factor pathwayinhibitor TFPI

Contact Tissue Factor + VIITissue Factor + VII

XIIIXIIIaa

XIIIXIII

ThrombinThrombin

FF(s(s

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, Protein

S, Antithrombin III

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Anticlotting Mechanisms

Protein C

Activated by

Thrombin/Thrombomodulin

Anticoagulant and fibrinolytic

activity.

Vitamin K and Protein S are

cofactors

Protein S

Contact Tissue Factor + VIITissue Factor + VII

XIIIXIIIaa

XIIIXIII

ThrombinThrombin

FibrinFibrin(strong(strong

FibrinogenFibrinogen FibrinFibrin(weak)(weak)

IXIX

XIXI

XIXIaaIXIXaa

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, Protein

S, Antithrombin III

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Fibrinolytic System

Plasmin

Produced from

Plasminogen by Tissue

Plasminogen activator

(TPA)Degrades Fibrin and

Fibrinogen (Fibrin

degradation products,

FDP)

Degrades Factors V, VIII,

IX, XI, and XII.

Activity is inhibited by

Anti lasmin.

FibrinolysisFibrinolysis

Plasminogen

Plasmin

Fibrin, fibrinogenFibrin, fibrinogen

ActivationActivation

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

Intrinsic: factor XIIa, HMWK,Intrinsic: factor XIIa, HMWK, kallkall

Exogenous:Exogenous: streptokinasestreptokinase

Fibrin, fibrinogenFibrin, fibrinogendegradation productsdegradation products

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Fibrinolytic Inhibitors

Antiplasmin Inactivates plasmin rapidly.

Acts slowly on plasmin

sequestered in the fibrin clot.

Inactivates factors XI and XII

slowly.

Plasminogen -Activator

Inhibitor-1(PAI-1) Inhibits the function of TPA

Also has some inhibitory

activity against urokinase,

plasmin, thrombin, activated

Protein C, factors and XII, and

kallikrein

FibrinolysisFibrinolysis

Plasminogen

Plasmin

Fibrin, fibrinogenFibrin, fibrinogen

ActivationActivation

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

Intrinsic: factor XIIa, HMWK,Intrinsic: factor XIIa, HMWK, kallkall

Exogenous:Exogenous: streptokinasestreptokinase

Fibrin, fibrinogenFibrin, fibrinogen

degradation productsdegradation products

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Hemostatic Balance

ATIIIClotting Factors

Tissue factor*

PAI-1

Antiplasmin

TFPI

Prot. C

Prot. S

Procoagulant Anticoagulant

Fibrinolytic System

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DIC

An acquired syndrome

characterized by systemic

intravascular

coagulation Coagulation is always the

initial event

DIC is not a disease but a

sign of an underlyingcondition

SYSTEMIC ACTIVATION

OF COAGULATION

Intravascular

deposition of

fibrin

Depletion of

platelets and

coagulationfactors

Thrombosis of

small and midsize

vessels

Bleeding

Organ failure DEATH

h l i l i i f l i (bl d l i )

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pathological activation of coagulation (blood clotting)

mechanisms that happens in response to a variety of

diseases

Is an alteration in the blood clotting mechanism:abnormacceleration of the coagulation cascade, resulting in

thrombosis

DIC leads to the formation of small blood clots inside t

blood vessels throughout the body. As the small clots

consume coagulation proteins and platelets, normal

coagulation is disrupted and abnormal bleeding occurs

from the skin (e.g. from sites where blood samples wertaken), the gastrointestinal tract, the respiratory tract an

surgical wounds.

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Conditions Associated With DIC

Malignancy

Leukemia

Metastatic disease

Lung , pancrease, prostrate, Cardiovascular

Post cardiac arrest

Acute MI

Prosthetic devices

Pulmonary

ARDS

Pulmonary embolism

Infectious/Septicemia Bacterial

Gm - / Gm +

Viral

CMV

Varicella

Hepatitis

Fungal

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Conditions Associated With DIC

Miscellaneous;

Intravascular hemolysis

Acute Liver Disease

Severe acidosis

Severe anoxia

Collagen vascular disease

Anaphylaxis

snake bite

Tissue Injury Trauma

Burns

extensive surgery

tissue necrosis

head trauma

Obstetric

Amniotic fluid emboli

Placental abruption

Eclampsia

Missed abortion

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Pathophysiology

In DIC, a systemic activation of the coagulationsystem

Platelets and clotting factors are consumed to

form the microthrombi (compromising bloodsupply to various organs) and

exhaustion of platelets and coagulation factors(results in hemorrhage). This is a disruption of

body homeostasis.

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Pathophysiology

Thrombosis-brief period ofhypercoagulability

1) Coagulation cascade isinitiated, causing widespreadfibrin formation

2) Microthrombi are depositedthroughout hemicrocirculatory

3) Fibrin deposits result in tissueischemia, hypoxia, necrosis

4) Leads to multi organdysfunction

Fibrinolysis-period ofhypocoagulability (the

hemorrhagic phase)1) Activates the complement

system

2) Byproducts of fibrinolysis(fibrin/fibrin degradation

products(FDP)) furtherenhance bleeding byinterfering with plateletaggregation, fibrinpolymerization, & thrombin

activity3) Leads to Hemorrhage

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Pathophysiology

(Porth, 2004)

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Clinical Manifestations of DIC

ORGAN ISCHEMIC HEMOR.

Skin Pur. FulminansGangrene

Acral cyanosis

Petechiae

Echymosis

Oozing

CNS Delirium/ComaInfarcts

Intracranial

bleeding

Renal Oliguria/AzotemiaCortical Necrosis

Hematuria

Cardiovascular MyocardialDysfxn

Pulmonary Dyspnea/HypoxiaInfarct

Hemorrhagic

lung

GI

Endocrine

Ulcers, Infarcts

Adrenal infarcts

Massive

hemorrhage.

Ischemic Findings

are earliest!

Bleeding is the m

obvious

clinical findin

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Clinical Manifestations of DIC

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Microscopic findings in DIC

Fragments

Schistocytes

Paucity of platelets

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Diagnosis/Lab FindingsTestPlatelet count

Factor assay

Fibrinogen

Fibrin degradation product

(FDP)

D-dimer

Prothrombin time (PT)

Activated PTT

Thrombin time

Antithrombin

Abnormality

Decreased

Decreased

Decreased

Increased

Increased

Prolonged

Prolonged

Prolonged

Decreased

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Laboratory diagnosis

Thrombocytopenia

plat count

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Treatment of DIC

Stop the triggering process .

The only proven treatment!

Supportive therapy

No specific treatments

Plasma and platelet substitution therapy

Anticoagulants

Physiologic coagulation inhibitors

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Platelet therapy

Indications

Active bleeding

Patient requiring invasive procedures

Patient at high risk for bleeding complications

Platelets

approximate dose 1 unit/10kg

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Plasma therapy

IndicationsActive bleeding

Patient requiring invasive procedures

Patient at high risk for bleeding complications

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

balanced amounts.

Usual dose is 10-15 ml/kg

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Blood

Replaced as needed to maintain adequate oxygen

delivery.

Blood loss due to bleeding

RBC destruction (hemolysis)

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Coagulation Inhibitor Therapy

Antithrombin III

Protein C concentrate

Tissue Factor Pathway Inhibitor (TFPI)

Heparin

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The major inhibitor of the coagulation cascade Levels are decreased in DIC.

Anticoagulant and antiinflammatory properties

Antithrombin III

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Protein C Concentrates

Inhibits Factor Va, VIIa and PAI-1 in conjunction with

thrombomodulin

Cryoprecipitate is given to replace fibrinogen and factors V and VII;

If fibrinogen is below 100mg/Dl

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Tissue Factor Pathway Inhibitor

Tissue factor is expressed on endothelial cells and

macrophages

TFPI complexes with TF, Factor VIIa,and Factor Xa to

inhibit generation of thrombin from prothrombin TF inhibition may also have antiinflammatory effects

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Heparin

May be indicated in patients with clinical

evidence of fibrin deposition or significant

thrombosis.

Generally contraindicated in patients withsignificant bleeding and CNS insults.

Dosing and route of administration varies.

Requires normal levels of ATIII.

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Antifibrinolytic Therapy

Rarely indicated in DIC

Fibrinolysis is needed to clear thrombi from the micro

circulation.

Use can lead to fatal disseminated thrombosis.

May be indicated for life threatening bleeding under the

following conditions:

bleeding has not responded to other therapies and:

laboratory evidence of overwhelming fibrinolysis.

evidence that the intravascular coagulation has ceased.

Agents: tranexamic acid, EACA

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NURSING DIAGNOSES Risk for deficient fluid volume related to bleeding

Risk for impaired skin integrity related to ischemia

or bleeding

Potential for excess fluid volume related to

excessive blood/ factor component replacement Ineffective tissue perfusion related to microthrombi

Anxiety and fear of the unknown and possible death

Acute pain r/t bleeding Ineffective tissue perfusion r/t bleeding, decre bld

flow

Avoid procedures/activities that can increase

i i l ( hi

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intracranial pressure (eg, coughing,

straining to have a bowel movement).

2. Monitor vital signs closely, including

neurologic checks:

a. Monitor hemodynamics

b. Monitor abdominal girth

c. Monitor urine output

3. Avoid medications that interfere withplatelet function if possible (eg, ASA,

NSAIDs, beta-lactam antibiotics).

4. Avoid rectal probes, rectal medications.

5. Avoid IM injections.6. Monitor amount of external bleeding

carefully

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Summary

DIC is a syndrome characterized systemic intravascular

coagulation.

Coagulation is the initial event and the extent of intravascular

thrombosis has the greatest impact on morbidity and mortality.

Important link between inflammation and coagulation.

Morbidity and mortality remain high.

The only proven treatment is reversal or control of the

underlying cause.