DESCRIPTION

• Normal coagulation: Series of local reactions among blood vessels, platelets, and clotting factors
• Disseminated intravascular coagulation (DIC) is systemic activation of coagulation and fibrinolysis by some other primary disease process.
• Coagulation system activation results in systemic circulation of thrombin and plasmin.
• Role of thrombin in DIC:
  • Tissue factor/factor VIII(a) activate the extrinsic pathway, leads to thrombin formation.
  • Thrombin circulates and converts fibrinogen to fibrin monomer.
  • Fibrin monomer polymerizes into fibrin (clot) in the circulation.
  • Clots cause microvascular and macrovascular thrombosis with resultant peripheral ischemia and end organ damage.
  • Platelets become trapped in clot with resultant thrombocytopenia.
• Role of plasmin in DIC:
  • Plasmin circulates systemically converting fibrinogen into fibrin degradation products (FDPs).
  • FDPs combine with fibrin monomers.
  • FDP-monomer complexes interfere with normal polymerization and impair hemostasis.
  • FDPs also interfere with platelet function.
• Role of impaired anticoagulation in DIC.
  • Failure of physiologic anticoagulation is necessary for DIC to occur.
  • Antithrombin III, protein C system, and tissue factor pathway inhibitor all impaired.
• Acute DIC—uncompensated form:
  • Clotting factors used more rapidly than body can replace them
  • Hemorrhage predominant clinical feature, which overshadows ongoing thrombosis
• Chronic DIC—compensated form:
  • Body able to keep up with pace of clotting factor consumption
  • Thrombosis predominant clinical feature

ETIOLOGY

• Precipitated by many disease states
• Complications of pregnancy:
  • Retained fetus
  • Amniotic fluid embolism
  • Placental abruption
  • Abortion
  • Eclampsia
  • HELLP syndrome
• Sepsis:
  • Gram negative (endotoxin-mediated meningococcemia)
  • Gram positive (mucopolysaccharide-mediated)
  • Other microorganisms (e.g., viruses, parasites)
• Trauma:
  • Crush injury
  • Severe burns
  • Severe head injury
  • Fat embolism
• Malignancy:
  • Solid tumor or metastatic disease
  • Hematologic malignancy (e.g., leukemia)
• Intravascular hemolysis:
  • Transfusion reactions
  • Massive transfusion
• Organ destruction:
  • Severe pancreatitis
  • Severe hepatic failure
• Vascular abnormalities:
  • Kasabach–Merritt syndrome
  • Large vascular aneurysm
• Thrombocytopenia:
  • Thrombotic thrombocytopenic purpura
  • Idiopathic thrombocytopenic purpura
• Miscellaneous:
  • Snake bites
  • Recreational drugs

[Outline]

• DESCRIPTION
• ETIOLOGY

SIGNS AND SYMPTOMS

• Excessive bleeding:
  • Petechiae
  • Purpura
  • Hemorrhagic bullae
  • Wound bleeding
  • Bleeding from venipuncture/arterial lines
  • Epistaxis
  • Hemoptysis
  • GI bleeding
• Excessive thrombosis:
  • Large vessels
  • Microvascular thrombosis and end organ dysfunction
  • Cardiac, pulmonary, renal, hepatic, CNS
  • Thrombophlebitis
  • Pulmonary embolus
  • Nonbacterial thrombotic endocarditis
  • Gangrene
  • Ischemic infarcts of kidney, liver, CNS, bowel
• Acute DIC:
  • Hemorrhagic complications predominate.
• Chronic DICL:
  • Thrombotic complications predominate.

History

• Previous history of bleeding disorder
• Pregnancy/last menstrual period
• History of malignancy or immunocompromised

Physical Exam

• Neurologic:
  • Altered MS, confusion, lethargy
• Cardiovascular:
  • Hypotension, tachycardia
• Respiratory:
  • Tachypnea, rhonchi, rales
• GI:
  • Upper or lower GI bleeding, abdominal distension
• GU:
  • Oliguria, hematuria
• Skin:
  • Petechiae, purpura, jaundice, necrosis

ESSENTIAL WORKUP

• Depends on precipitating illness
• Diagnosis generally not made in ED

DIAGNOSIS TESTS & INTERPRETATION

Lab

• Platelet count:
  • Important to note rapid decrease
  • < 100,000/mm³
  • May be normal in chronic DIC
• Prothrombin time (PT)/partial thromboplastin time (PTT):
  • Increased
  • May be normal in chronic DIC
• Fibrinogen:
  • Decreased
  • < 150 mg/dL in 70%
  • Low sensitivity, as levels can remain normal
  • May be normal in chronic DIC
• FDPs:
  • Increased
  • > 40 µg/mL
• D-dimer increased
• CBC/peripheral smear:
  • Red cell fragments
  • Low platelets
  • Peripheral smear confirms disease in chronic DIC
• Electrolytes, BUN, creatinine, glucose:
  • Elevated BUN, creatinine owing to renal insufficiency
• ABGs:
  • Oxygen, acid–base status
• ISTH scoring system
  • Underlying disorder associated with DIC
    • no = 0, yes = 2
  • Platelet count
    • > 100 = 0, < 100 = 1, < 50 = 2
  • Fibrin markers (D-dimer, FDP)
    • Normal = 0, moderate increase = 1, strong increase = 2
  • Prolonged PT
    • < 3 = 0, > 3 but < 6 = 1, > 6 = 2
  • Fibrinogen
    • 1 g/L = 0, < 1 g/L = 1
  • Score > 5 overt DIC, associated with increased mortality.

Imaging

• CXR for suspected pneumonia
• Head CT for altered mental status
• OB US in pregnant patients

DIFFERENTIAL DIAGNOSIS

• Inherited coagulation disorders:
  • Factor deficiencies
• Other acquired coagulation disorders:
  • Anticoagulant therapy
  • Drugs
  • Hepatic disease
  • Vitamin K deficiency
  • Massive blood loss
• Platelet dysfunction:
  • TTP/HUS
  • HIT
  • ITP
• Platelet dysfunction:
  • TTP/HUS
  • HI

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

INITIAL STABILIZATION/THERAPY

• Airway management and resuscitation measures:
  • Control bleeding
  • Establish IV access
  • Restore and maintain circulating blood volume.
• Initiate therapy of precipitating disease:
  • Antibiotics in sepsis
  • Evacuate uterus of retained products of conception
  • Chemotherapy in malignancy
  • Débridement of devitalized tissue in trauma

ED TREATMENT/PROCEDURES

• Therapy of DIC is controversial and should be individualized based on:
  • Age
  • Hemodynamic status
  • Severity of hemorrhage
  • Severity of thrombosis
• Involve admitting service before initiating specific DIC therapy.
• Replace depleted blood components:
  • Fresh frozen plasma (FFP):
    • For prolonged PT
    • Provides clotting factors and volume replacement
    • Dose: 2 U or 10–15 mL/kg
  • Platelets:
    • If platelet count < 20,000 or platelet count < 50,000 with ongoing bleeding
    • Dose: 1 U/10 kg body weight
  • Cryoprecipitate:
    • Higher fibrinogen content than whole plasma
    • For severe hypofibrinogenemia (< 50 mg/dL) or for active bleeding with fibrinogen < 100 g/dL
    • Dose: 8 U
  • Recombinant factor VIIa
    • Successful use reported, benefit and safety unknown.
  • Washed packed cells
  • Albumin
  • Nonclotting volume expanders
• Inhibit intravascular clotting with heparin:
  • Use is controversial.
  • Consider when thrombosis predominates.
  • May be effective in mild to moderate DIC
  • Efficacy undetermined in severe DIC. Possible indications:
    • Purpura fulminans (gangrene of digits, extremities)
    • Acute promyelocytic leukemia
    • Dead fetus syndrome—several weeks after intrauterine fetal death
    • Thromboembolic complications of large vessels
    • Before surgery with metastatic carcinoma
  • Administer activated protein C (controversial):
    • No mortality benefit.
  • Antithrombin
    • No mortality benefit found in patients also receiving heparin.
    • Lack of evidence to support use at this time.
• Inhibit fibrinolysis:
  • Block secondary compensatory fibrinolysis that accompanies DIC
  • Use complicated by severe thrombosis
  • Use only when DIC accompanied by primary fibrinolysis:
    • Promyelocytic leukemia
    • Giant hemangioma
    • Heat stroke
    • Amniotic fluid embolism
    • Metastatic carcinoma of prostate
  • Initiate in extreme cases only:
    • Profuse bleeding not responding to replacement therapy
    • Excessive fibrinolysis present (rapid whole blood lysis/short euglobulin lysis time)
    • E-aminocaproic acid (EACA)
    • Tranexamic acid

MEDICATION

Specific DIC treatment is usually not initiated in the ED. Underlying precipitating diseases should be treated initially:

• Heparin:
  • Low-dose regimen: 5–10 U/kg/h IV for causes where thrombosis predominates.

[Outline]

• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

DISPOSITION

Admission Criteria

Severe precipitating illness in combination with DIC requires ICU admission.

Discharge Criteria

None

FOLLOW-UP RECOMMENDATIONS

Follow-up involves following platelets and coagulation factors.

[Outline]

• DISPOSITION
• FOLLOW-UP RECOMMENDATIONS

• Suspect DIC as a complicating factor in severe, life-threatening illness.
• Establish early clinical suspicion since the sequelae of DIC can be devastating.
• Remember to consider treating the underlying cause of DIC when the thromboembolic and bleeding complications of the process seem to be dominating the clinical picture.

ICD9

286.6 Defibrination syndrome

ICD10

D65 Disseminated intravascular coagulation

[Outline]

• ICD9
• ICD10

• Bick RL. Disseminated intravascular coagulation current concepts of etiology, pathophysiology, diagnosis, and treatment. Hematol Oncol Clin North Am. 2003;17(1):149–176.
• Levi M. Disseminated intravascular coagulation. Crit Care Med. 2007;35:2191–2195.
• Levi M, Toh CH, Thachil J, et al. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol. 2009;145(1):24–33.
• Levi M, van der Poll T. Disseminated intravascular coagulation: A review for the internist. Intern Emerg Med. 2013;8:23–32.
• Rodgers GM. Acquired coagulation disorders. In: Greer JP, Foerster J, Rodgers GM, et al., eds. Wintrobe's Clinical Hematology. 12th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:1422–1455.

See Also (Topic, Algorithm, Electronic Media Element)

• Sepsis
• Idiopathic Thrombocytopenic Purpura
• Thrombotic Thrombocytopenic Purpura

Steven H. Bowman

Ernesto J. Romo