Disseminated Intravascular Coagulation

DIC
An

acquired syndrome characterized by systemic intravascular coagulation

Thrombosis
Platelet Red Blood Cell

Fibrin

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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 Plasminogen Activator Tissue thromboplastin/Tissue factor

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Coagulation Pathways
Intrinsic Pathway Extrinsic Pathway

Coagulation

Contact

IX

TF Pathway

XI XIIa HKa

TF-VII a PL PL (Tenase) VIIIa

Tissue Factor + VII X

Common Pathway

Intrinsic Pathway Extrinsic Pathway Common Pathway Contact Pathway Tissue Factor Pathway
Primary

Prothrombin XIa IXa Xa PL Va Thrombin Fibrinogen Fibrin

(weak)

XIII

(Prothrombinase) Protein C, Protein S, Antithrombin III

XIIIa

Fibrin
(strong)

factor in DIC

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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.

Coagulation Pathways
Intrinsic Pathway Contact Extrinsic Pathway

IX

TF Pathway

XI XIIa HK a XIa IXa

TF-VIIa PL PL (Tenase) VIIIa

Tissue Factor + VII X

Common Pathway

Prothrombin PL Va Thrombin Fibrinogen Fibrin

(weak)

Activity

is enhanced by

Xa

XIII

(Prothrombinase) Protein C, Protein S, Antithrombin III

heparin.

XIIIa

Tissue factor pathway inhibitor TFPI

Fibrin
(strong)

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Anticlotting Mechanisms
5

Protein C
Activated

Coagulation Pathways
Intrinsic Pathway Contact Extrinsic Pathway

by Thrombin/Thrombomodulin Anticoagulant and fibrinolytic activity. Vitamin K and Protein S are cofactors

IX

TF Pathway

XI XIIa HKa XIa IXa

TF-VIIa PL PL (Tenase) VIIIa

Tissue Factor + VII X

Common Pathway

Prothrombin PL Va Thrombin Fibrinogen Fibrin

(weak)

Xa

XIII

(Prothrombinase) Protein C, Protein S, Antithrombin III

Protein S

XIIIa

Fibrin
(strong)

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Fibrinolytic System
7

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 Antiplasmin.

Fibrinolysis
Plasminogen Extrinsic: t-PA, urokinase Activation Intrinsic: factor XIIa, HMWK, kallikrein Exogenous: streptokinase Fibrin, fibrinogen Plasmin Fibrin, fibrinogen degradation 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.

Fibrinolysis
Plasminogen Extrinsic: t-PA, urokinase Activation Intrinsic: factor XIIa, HMWK, kallikrein Exogenous: streptokinase Fibrin, fibrinogen Plasmin Fibrin, fibrinogen degradation products

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

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Hemostatic Balance

PAI-1 Antiplasmin Tissue factor* Clotting Factors

Prot. S

Prot. C TFPI
Fibrinolytic System

ATIII

Procoagulant

Anticoagulant

DIC

SYSTEMIC ACTIVATION OF COAGULATION

An acquired syndrome characterized by systemic intravascular coagulation Coagulation is always the initial event DIC is not a disease but a sign of an underlying condition

Intravascular deposition of fibrin

Depletion of platelets and coagulation factors

Thrombosis of small and midsize vessels

Bleeding

Organ failure

DEATH

pathological activation of coagulation (blood clotting) mechanisms that happens in response to a variety of diseases Is an alteration in the blood clotting mechanism:abnormal acceleration of the coagulation cascade, resulting in thrombosis DIC leads to the formation of small blood clots inside the 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 were taken), the gastrointestinal tract, the respiratory tract and surgical wounds.

Conditions Associated With DIC

Malignancy
Leukemia Metastatic

Pulmonary
ARDS Pulmonary

disease Lung , pancrease, prostrate,

embolism

Infectious/Septicemia
Bacterial

Cardiovascular
Post

cardiac arrest Acute MI Prosthetic devices

Gm - / Gm +

Viral

CMV Varicella Hepatitis

Fungal

Conditions Associated With DIC

Miscellaneous;
Intravascular

Tissue Injury
Trauma Burns extensive

hemolysis Acute Liver Disease Severe acidosis Severe anoxia Collagen vascular disease Anaphylaxis snake bite

surgery tissue necrosis head trauma

Obstetric
Amniotic

fluid emboli Placental abruption Eclampsia Missed abortion

Pathophysiology
In DIC, a systemic activation of the coagulation system Platelets and clotting factors are consumed to form the microthrombi (compromising blood supply to various organs) and exhaustion of platelets and coagulation factors (results in hemorrhage). This is a disruption of body homeostasis.

Pathophysiology
Fibrinolysis-period of Thrombosis-brief period of hypocoagulability (the hypercoagulability hemorrhagic phase) 1) Coagulation cascade is initiated, causing widespread 1) Activates the complement system fibrin formation 2) Microthrombi are deposited 2) Byproducts of fibrinolysis (fibrin/fibrin degradation throughout he products(FDP)) further microcirculatory enhance bleeding by 3) Fibrin deposits result in tissue interfering with platelet ischemia, hypoxia, necrosis aggregation, fibrin 4) Leads to multi organ polymerization, & thrombin dysfunction activity 3) Leads to Hemorrhage

Pathophysiology

(Porth, 2004)

Clinical Manifestations of DIC

Ischemic Findings are earliest!

ORGAN Skin CNS Renal Cardiovascular Pulmonary GI Endocrine

ISCHEMIC
Pur. Fulminans Gangrene Acral cyanosis Delirium/Coma Infarcts Oliguria/Azotemia Cortical Necrosis Myocardial Dysfxn Dyspnea/Hypoxia Infarct Ulcers, Infarcts Adrenal infarcts

HEMOR.
Petechiae Echymosis Oozing Intracranial bleeding Hematuria

Hemorrhagic lung Massive hemorrhage.

Bleeding is the most obvious clinical finding

Clinical Manifestations of DIC

Microscopic findings in DIC

Fragments Schistocytes Paucity of platelets

Test Platelet count Factor assay Fibrinogen

Diagnosis/Lab Findings Abnormality

Decreased Decreased Decreased Increased Increased

Fibrin degradation product (FDP) D-dimer Prothrombin time (PT) Activated PTT Thrombin time Antithrombin

Prolonged Prolonged Prolonged Decreased

Laboratory diagnosis

Thrombocytopenia
plat

count <100,000 or rapidly declining

Prolonged clotting times (PT, APTT) Presence of Fibrin degradation products or positive D-dimer Low levels of coagulation inhibitors
AT

III, protein C V,VIII,X,XIII

Low levels of coagulation factors

Factors

Fibrinogen levels not useful diagnostically

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

Platelet therapy

Indications
Active

bleeding Patient requiring invasive procedures Patient at high risk for bleeding complications

Platelets
approximate

dose 1 unit/10kg

Plasma therapy

Indications
Active

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

Blood

Replaced as needed to maintain adequate oxygen delivery.

Blood

loss due to bleeding RBC destruction (hemolysis)

Coagulation Inhibitor Therapy

Antithrombin III Protein C concentrate Tissue Factor Pathway Inhibitor (TFPI) Heparin

Antithrombin III

The major inhibitor of the coagulation cascade

Levels

are decreased in DIC. Anticoagulant and antiinflammatory properties

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

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

Heparin
May be indicated in patients with clinical evidence of fibrin deposition or significant thrombosis. Generally contraindicated in patients with significant bleeding and CNS insults. Dosing and route of administration varies. Requires normal levels of ATIII.

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

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 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 with platelet 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

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.