DESCRIPTION

• Disseminated intravascular coagulopathy (DIC) is an acquired hemorrhagic and thrombotic syndrome characterized by systemic activation of coagulation pathways resulting in intravascular fibrin formation, microangiopathic thrombosis, and subsequent depletion of coagulation factors and platelets.
• DIC is always secondary to an underlying etiology.
  • Widespread deposition of microthrombi can compromise perfusion and lead to organ failure.
  • Ongoing activation and consumption of coagulant factors and platelets can result in diffuse and profuse bleeding.
  • DIC can progress rapidly into life-threatening multiorgan failure; identifying the underlying etiology is vital to management.

EPIDEMIOLOGY

• Most commonly secondary to infection, hematologic malignancy, and head trauma
• DIC may occur in 30–60% of patients with sepsis (>50% of patients with septic shock) and in 30–40% of patients with head trauma and develops in an estimated 1% of all hospitalized patients.
• DIC occurs at all ages and in all races, and no particular sex predisposition has been established.

ETIOLOGY

Most common causes are sepsis (particularly gram-negative), hypotensive shock, and trauma.

• Sepsis/severe infection
  • Bacterial: gram-negative and gram-positive
  • Malaria: Plasmodium falciparum
  • Fungal: Aspergillus
  • Rickettsial: Rocky Mountain spotted fever
  • Viral
• Trauma
  • Multiple fractures with fat emboli
  • Massive soft tissue injury
  • Severe head trauma
  • Multiple gunshot wounds
• Malignancies
  • Acute promyelocytic leukemia
  • Widespread solid tumors (e.g., neuroblastoma, adenocarcinoma)
• Obstetric
  • Retained intrauterine fetal demise
  • Preeclampsia/eclampsia
  • Amniotic fluid embolism
  • Abruptio placentae
  • Posthemorrhagic shock
• Neonatal
  • Necrotizing enterocolitis
  • Perinatal asphyxia
  • Amniotic fluid aspiration
  • Obstetric complications (see above)
  • Sepsis (bacterial and viral)
  • Erythroblastosis fetalis
  • Respiratory distress syndrome
• Vascular malformations
  • Kasabach-Merritt syndrome
  • Large vascular aneurysms
• Miscellaneous
  • Acute hemolytic transfusion reaction
  • Snake bite
  • Homozygous protein C or S deficiency (purpura fulminans)
  • Transplant rejection
  • Severe collagen vascular disease
  • Recreational drugs
  • Profound shock or asphyxia
  • Hypothermia or hyperthermia
  • Extensive burn injuries
  • Fulminant hepatitis/hepatic failure
  • Severe pancreatitis

PATHOPHYSIOLOGY

• Not an isolated disorder in itself; occurs as a result of various initiating events
• May be acute (e.g., meningococcemia) or chronic (e.g., malignancy/leukemia)
• Dysregulated activation of the coagulation system and platelets, along with dysregulation of the endothelium, results in consumptive coagulopathy and microvascular thrombosis.
  • There is a systemic intravascular deposition of fibrin as a result of increased thrombin generation, platelet activation, suppression of anticoagulant pathways, impaired or enhanced fibrinolysis (depending on the underlying etiology), and activation of inflammatory pathways.
  • The initiation of coagulation activation leading to thrombin formation in DIC is mediated via the tissue factor/factor VIIa pathway.
  • The tissue factor/factor VIIa pathway is activated via tissue factor expression from damaged endothelial cells.
  • Anticoagulant pathways are diminished because of a decrease in the plasma levels of antithrombin and the protein C system through impaired production and increased destruction.
  • The endothelium loses its anticoagulant properties by losing glycocalyx, reducing nitric oxide (NO), prostaglandin I2 (PG I2), and tissue factor pathway inhibitor (TFPI) release.
  • Hypofibrinolysis is mediated by increased plasminogen activator inhibitor-1 (PAI-1) release from damaged endothelium and platelets as well as TFPI activity.
  • Complement-mediated lysis of cells and/or bacterial pathogens release damage-associated molecular patterns (DAMPs) that directly activate platelets, leading to further activation of coagulation, thrombin formation, and thrombocytopenia.
  • Increased release of von Willebrand factor and decreased circulating levels of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) also contribute to increased platelet adhesion during sepsis.
  • Activated platelets bind to neutrophils and induce neutrophil extracellular traps (NETs).
  • Extracellular vesicles from damaged endothelium and activated platelets and leukocytes contribute to activation of inflammation and coagulation.