Disseminated Intravascular Coagulation (DIC)

Essentials of Diagnosis

• Associated with cancer, infection, trauma, and obstetrical patients

• Prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT)

• Thrombocytopenia

• Low/declining fibrinogen levels

General Considerations

• Results from uncontrolled local or systemic activation of coagulation, which leads to depletion of coagulation factors and fibrinogen and often results in thrombocytopenia as platelets are activated and consumed

• Numerous disorders are associated with DIC

  • Sepsis (in which coagulation is activated by presence of lipopolysaccharide)

  • Cancer

  • Trauma

  • Burns

  • Pregnancy-associated complications (in which tissue factor is released)

• Aortic aneurysm and cavernous hemangiomas may promote localized intravascular coagulation

• Snake bites may result in DIC due to the introduction of exogenous toxins

• The HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is a severe form of DIC with a particularly high mortality rate that occurs in peripartum women

Symptoms and Signs

• Bleeding usually occurs at multiple sites, such as intravenous catheters or incisions, and may be widespread (purpura fulminans)

• Malignancy-related DIC may manifest principally as thrombosis (Trousseau syndrome)

Differential Diagnosis

• Severe liver disease

• Thrombotic thrombocytopenic purpura

• Sepsis-induced thrombocytopenia or anemia

• Heparin-induced thrombocytopenia

• Other microangiopathic hemolytic anemia (eg, prosthetic valve hemolysis)

Laboratory Tests

• Thrombocytopenia

• In early DIC

  • Platelet count and serum fibrinogen levels often initially remain within the normal range

  • Progressive thrombocytopenia (rarely severe)

  • Prolongation of PT

  • Decrease in fibrinogen levels

  • Elevation in aPTT

  • D-dimer levels typically elevated

  • Schistocytes on the blood smear in 10–20% of patients

• In the HELLP syndrome

  • Elevated liver transaminases

  • Kidney injury due to gross hemoglobinuria and pigment nephropathy

• Malignancy-related DIC may feature normal platelet counts and coagulation studies but a dropping platelet count and fibrinogen, with a rising INR, are often seen

Medications

• Underlying causative disorder must be treated (eg, antimicrobials, chemotherapy, surgery, or delivery of conceptus)

• If clinically significant bleeding is present, hemostasis must be achieved; following is a strategy of managing DIC:

  • Assess for underlying cause of DIC and treat

  • Establish baseline platelet count, PT, aPTT, D-dimer, fibrinogen

  • Transfuse blood products if ongoing bleeding or high risk of bleeding

    • Platelets: goal > 20,000/mcL (most patients) or > 50,000/mcL (severe bleeding, eg, intracranial hemorrhage)

    • Cryoprecipitate: goal fibrinogen level > 80–100 mg/dL

    • Fresh frozen plasma: goal PT and aPTT < 1.5 × normal

    • Packed red blood cells: goal hemoglobin > 8 g/dL or improvement in symptomatic anemia

  • Follow platelets, aPTT/PT, fibrinogen every 4–6 hours or as clinically indicated

  • Heparin (initial infusion, 5–10 units/kg/h)

    • May be considered when bleeding is persistent

    • Do not administer bolus

    • Contraindicated if platelets cannot be maintained at > 50,000/mcL, in cases of gastrointestinal or central nervous system (CNS) bleeding, in conditions that may require surgical management, or placental abruption

  • Follow laboratory parameters every 4–6 hours until DIC resolved and underlying condition successfully treated

• Goal platelet count with platelet infusion therapy is > 20,000–30,000/mcL for most cases or > 50,000/mcL for serious bleeding, such as intracranial bleeding

• Fresh frozen plasma (FFP) should be given only to patients with prolonged aPTT and PT and significant bleeding

• Cryoprecipitate may be given for bleeding and for fibrinogen levels < 80–100 mg/dL

• In some cases of refractory bleeding

  • A low-dose heparin infusion (eg, 5 units/kg/h, with no bolus) can be considered and uptitrated as clinically appropriate

  • However, heparin is contraindicated if the platelet count cannot be maintained at ≥ 50,000/mcL and in cases of CNS hemorrhage, gastrointestinal bleeding, placental abruption, and any other condition that is likely to require imminent surgery

  • Fibrinolysis inhibitors may be considered in some cases

• Patients with Trousseau syndrome require

  • Treatment of the underlying malignancy

  • Administration of unfractionated heparin or subcutaneous therapeutic-dose LMWH

• Oral anti-Xa agents or oral direct thrombin inhibitors can be considered once patient is stabilized with parenteral heparin or LMWH

• Immediate initiation of medical therapy (usually within 24 hours of diagnosis) is required for patients with acute promyelocytic leukemia (APL)–associated DIC, along with administration of blood products as clinically indicated

Therapeutic Procedures

• Treatment of underlying disorder

• Mild DIC requires no specific therapy

• Treatment of the HELLP syndrome must include evacuation of the uterus (eg, delivery of a term or near-term infant or removal of retained placental or fetal fragments)

Follow-Up

• PT, aPTT, fibrinogen level, and platelet count should be monitored at least every 6–8 hours in acutely ill patients with DIC

Prognosis

• Prognosis is that of the underlying disease

When to Refer

• Patients with diffuse bleeding that is unresponsive to administration of blood products should be evaluated by a hematologist

• All patients should be cared for by a hematologist before starting treatment with heparin or LMWH

When to Admit

• Most patients with DIC are hospitalized when it is detected