Definition

A complex hemostatic defect arising from a variety of inciting causes that leads to uncontrolled activation and consumption of clotting factors. It results in widespread formation of microthrombi with clinical manifestations of thrombosis and/or hemorrhage.

Pathophysiology

• DIC represents a complication of a variety of primary conditions. It begins with a hypercoagulable state that leads to microthrombi in many small vessels.
• The primary conditions primarily act through increased exposure/production of TF (Factor III) which activates the extrinsic coagulation pathway.
• TF is normally restricted from intravascular exposure. It is usually exposed when endothelium is damaged revealing subendothelial tissue, which localizes coagulation. Increased exposure/production mainly occurs through widespread endothelial injury and/or increased production secondary to inflammation.
• Inflammation activates endothelial cells, platelets, and monocytes leading to membrane expression of TF. Inflammatory cytokines also induce vesiculation of these membranes releasing large quantities of microparticles into circulation that are enriched with both TF and PS and that facilitate extensive dissemination of coagulation. Some neoplastic cells constitutively produce membrane TF and also release microparticles.
• Microparticles provide a suitable membrane surface for amplifying intrinsic and common pathway coagulation, potentially leading to uncontrolled production of thrombin that overwhelms coagulation inhibitors (AT, APC, TFPI). Thrombin's conversion of fibrinogen to fibrin contributes to vascular occlusion.
• Widespread microthrombus formation consumes coagulation factors and platelets while initiating fibrinolysis. By-products of fibrinolysis (FDPs) have anticoagulant properties and inhibit platelet function. Hemorrhage at a variety of sites can follow.
• Uncontrolled progression leads to widespread tissue hypoxia, multi-organ dysfunction, and death.

Systems Affected

Multisystemic syndrome

Genetics

N/A

Incidence/Prevalence

Associated with severe systemic disease, often in the terminal stages

Geographic Distribution

N/A

Signalment

Causes

• Gastric dilatation-volvulus
• Heart failure
• Heartworm disease
• Heat stroke
• Hemolysis, especially immune mediated
• Hemorrhagic gastroenteritis
• Infectious diseases, systemic (especially endotoxemia)
• Inflammation, severe-regardless of underlying cause
• Liver disease, if severe (e.g., ICH, xylitol toxicity in dogs; lipidosis in cats)
• Malignancies, especially hemangiosarcoma, mammary carcinoma, and pulmonary adenocarcinoma in dogs and lymphoma in cats
• Pancreatitis
• Protein-losing nephropathy (nephrotic syndrome)
• Shock, hypoxia, acidosis
• Thrombocytopenia, especially immune mediated
• Transfusion incompatibility
• Trauma
• Venom

Risk Factors

Vary with cause

Differential Diagnosis

• Key differentials: immune-mediated thrombocytopenia, anticoagulant toxicity, coagulation factor deficiency, paraproteinemia.
• Highly variable diagnostic pattern includes thrombocytopenia, prolonged clotting tests (PT, APTT), decreased fibrinogen, decreased AT, and increased fibrinolysis (FDPs, D-dimers). At least three abnormalities in animals affected by a predisposing condition (see “Causes”) is considered diagnostic.
• Suspect DIC any time thrombocytopenia and prolonged clotting tests are seen together.
• Patients showing predisposing conditions should have laboratory monitoring every 24–48 hours. A sudden drop in platelet count and a 20–30% prolongation in APTT is very suspicious for DIC.
• Hepatic insufficiency may mimic DIC pattern. Decreased production of clotting factors is common. Decreased clearance of normal fibrin(ogen)olytic by-products may increase FDP values. Mild idiopathic thrombocytopenia may also be seen. Spontaneous bleeding is uncommon unless DIC is present.

CBC/Biochemistry/Urinalysis

• Inflammatory leukogram, often with a stress component.
• Thrombocytopenia; very consistent finding in dogs, less reliable in cats.
• Anemia is possible. RBC fragmentation (schistocytes) is a supportive finding.
• Biochemical changes reflect affected organs.

Other Laboratory Tests

• Prolonged clotting tests (PT, APTT); APTT is more sensitive.
• Hypofibrinogenemia, although inflammatory increase may mask consumption.
• Increased FDPs and D-dimers. D-dimers are very sensitive. DIC is unlikely if D-dimers are low/negative. Neither test is specific enough alone to diagnose DIC.
• Decreased AT; may be a positive acute phase reactant in cats, masking consumption.
• TEG reportedly identifies hypercoagulable and hypocoagulable states in DIC. Case fatality rate is significantly higher in the hypocoagulable state.

Imaging

N/A

Diagnostic Procedures

None

Pathologic Findings

• Usually related to the primary disease or DIC-affected organs
• Petechiae common

Appropriate Health Care

• Requires intensive inpatient treatment.
• Aggressive treatment of the primary disease is essential (e.g., antimicrobials for sepsis).

Nursing Care

• Maintain tissue perfusion and oxygenation using fluids, transfusions, and oxygen therapy.
• Restore depleted factors by blood/plasma transfusions. Use fresh frozen plasma (6-20 mL/kg) to correct bleeding due to factor deficiency.

Activity

Limited by the disease severity

Diet

Maintain nutritional support as appropriate for the clinical condition of the patient.

Client Education

Inform the owner that the condition is life-threatening with a guarded to poor prognosis.

Surgical Considerations

Related to primary disease. Plasma or whole blood transfusion to restore clotting factors is a presurgical consideration. Surgery may be contraindicated with uncontrolled bleeding.

Drug(s) Of Choice

• Successful drug protocols are mostly anecdotal and traditionally use heparin to effect (clinical improvement, test results).
• Heparin binds to and potentiates the action of AT. Plasma or blood transfusions are often needed to replenish AT for heparin to be effective.
• Heparin dosage depends on severity of signs and lab changes.
• Mild to moderate disease: heparin at 5–200 U/kg SC q8h or IV (q8h or continuous infusion)
• Severe disease: heparin at 300–1,000 U/kg SC q8h or IV (q8h or continuous infusion)

Contraindications

Inhibitors of fibrinolysis should not be used. Fibrinolysis is important in the clearance of thrombi.

Precautions

• High doses of heparin may cause fatal hemorrhage.
• Watch for overhydration in cases with renal or pulmonary compromise.
• Corticosteroids impair function of mononuclear phagocytes, possibly delaying removal of activated coagulation factors and FDPs. Avoid prolonged use.
• Use of antiplatelet medications (aspirin, clopidogrel) in thrombocytopenic patients warrants caution for hemorrhage even though platelet activation is a part of DIC pathogenesis.

Possible Interactions

None

Alternative Drug(s)

Low molecular weight heparin: many forms with variable activity are available. Fewer complications reported but very expensive. Most information is anecdotal.

Patient Monitoring

• Clinical improvement and the arrest of bleeding are key positive findings.
• Daily lab testing (e.g., coagulation tests, fibrinogen, platelet counts) is warranted in severe cases to identify positive or negative trends. Less frequent testing may suffice in milder cases.
• Coagulation times and fibrinogen often return to normal more rapidly than FDPs and platelet counts.

Prevention/Avoidance

• Related to primary disease.

Possible Complications

Aside from the primary disease, DIC affected organs may have permanent dysfunction or marginal reserve capacity.

Expected Course and Prognosis

Mortality rates for dogs range from 50% to 77%. For cats, rates may be >90%.

Associated Conditions

See “Causes”

Age-Related Factors

Related to primary disease

Zoonotic Potential

None

Pregnancy/Fertility/Breeding

Unlike in humans, obstetric complications are not a common cause in dogs and cats.

Synonyms

• Consumption coagulopathy
• DIC

See Also

• Coagulation Factor Deficiency
• Thrombocytopenia

Abbreviations

• APC = activated protein C
• APTT = activated partial thromboplastin time
• AT = antithrombin
• DIC = disseminated intravascular coagulation
• FDP = fibrin degradation product
• ICH = infectious canine hepatitis
• PS = phosphatidylserine
• PT = prothrombin time
• RBC = red blood cell
• TF = tissue factor
• TFPI = tissue factor pathway inhibitor
• TEG = thromboelastography
• TNF = tumor necrosis factor

Client Education Handout Available Online