Coagulation
Acquired bleeding disorders
Disseminated intravascular coagulation (DIC)

Author: Kendall Crookston, M.D., Ph.D, Lizabeth Rosenbaum, M.D. and Julie Gober-Wilcox, M.D. (see Authors page)

Revised: 2 March 2016, last major update August 2010

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Disseminated intravascular coagulation [title]
Definition / General
  • A common acquired syndrome arising from various causes (see etiology below), characterized by massive, sustained and excessive activation of coagulation with the eventual inundation (overwhelming) of the anticoagulant and fibrinolytic systems
  • Leads to disseminated microthrombi and tissue ischemia; consumption of platelets, coagulation factors and natural anticoagulants; and variable bleeding
  • Activation of inflammatory pathways via cytokines also plays a role
  • Ultimately free, circulating, unopposed thrombin and plasmin are generated (the two key agents responsible for DIC) which then leads to:
    • Activation and consumption of platelets, coagulation factors, fibrinogen and fibrin
    • Consumption and depletion of anticoagulant proteins (protein C, protein S and antithrombin)
    • Generation of D-dimers and fibrin degradation productsn
    • Formation of microthrombi leading to tissue ischemia (large thrombi can also be formed, particularly in cancer patients)
    • Schistocytes (fragmented red blood cells) are formed as red blood cells are severed flowing through fibrin strands (microthrombi within vasculature)
    • Variable bleeding
Diagrams / Tables

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Key events in DIC

Epidemiology
  • 1% of hospitalized patients are estimated to develop DIC
  • 20% of patients with Acute Respiratory Distress Syndrome (ARDS) develop DIC and 20% of patients with DIC develop ARDS
  • 20% of patients with gram-negative sepsis develop DIC

  • Other causes:
    • Infection / sepsis: most common cause, includes bacterial, viral, fungal, rickettsial and protozoal organisms
    • Tissue damage: trauma, burns
    • Malignancy: solid and hematologic
    • Obstetric complications: abruptio placentae, retained dead fetus syndrome, preeclampsia / eclampsia, amniotic fluid embolism, acute fatty liver of pregnancy, septic abortion
    • Miscellaneous: near drowning, fat embolism, snake bites, aortic aneurism, acute hemolytic transfusion reaction, adult respiratory distress syndrome, giant hemangioma, homozygous protein C deficiency)
Clinical Features
  • Patients can have either bleeding or thrombosis or both
  • Septic patients are more likely to have thrombosis than bleeding
  • If severe and prolonged, will eventually lead to multiorgan dysfunction/failure
  • Causes of DIC can be acute (meningococcemia) or chronic (retained dead fetus), localized (abdominal aortic aneurysm) or systemic (acute promyelocytic leukemia)
  • Chronic causes of DIC are typically malignancy, liver disease, retained dead fetus syndrome, abdominal aortic aneurysm, giant hemangioma and head trauma
  • Bleeding can present as surgical site, venipuncture site or mucocutaneous bleeding (most common)
    • Gastrointestinal bleeding, CNS bleeding, hematuria or ecchymoses
  • Thrombosis can present as purpura fulminans (manifestation of subdermal microthrombi with skin necrosis)
    • Cold, pulseless limb
    • Sudden loss of vision
    • Oliguria
    • Mental status changes, seizures, behavioral changes or adrenal insufficiency
Laboratory
  • Prolonged PT and PTT
  • Elevated D-dimers (Am J Clin Pathol 2004;122:178) and other fibrin degradation products (but D-dimer may be falsely positive in HIV+ Castleman’s disease due to interference from monoclonal gammopathy (Arch Pathol Lab Med 2004;128:328)
  • Fall in platelet count (usually not lower than 30,000 - 40,000 x 109/L)
  • Drop in fibrinogen
  • Presence of schistocytes on peripheral blood smear (not specific for DIC)
  • With chronic causes, fibrinogen and platelets may actually be elevated as acute phase reactants
  • All coagulation factors may be variably decreased due to factor activation and consumption
  • Multiorgan dysfunction may manifest as elevated cardiac enzymes or elevated BUN / creatinine
  • Baseline coagulation studies and serial follow-up are needed to follow the trends
Prognostic Factors
  • One multicenter study of critically ill patients with DIC found that the 28 day mortality was 21.9%, which was significantly higher than non-DIC patients (11.2%) (Crit Care Med 2008;36:145)
  • Another study found the mortality rate was significantly higher in sepsis patients than trauma patients (Thromb Haemost 2008;100:1099)
Case Reports
Treatment
  • Treat underlying disease
  • Keep fibrinogen levels above 100 mg/dL with cryoprecipitate or fresh frozen plasma
  • Monitor PT, PTT, platelet count, fibrinogen and possibly antithrombin levels
  • If bleeding predominates, replace coagulation factors and fibrinogen with fresh frozen plasma (FFP) and cryoprecipitate
    • Consider plasmapheresis, platelet-transfusions and immunoabsorption
  • If platelet count is lower than 50,000 x 109/L with active bleeding, or lower than 10,000 x 109/L, give platelet infusion
  • If thrombosis predominates (chronic DIC), heparinization should be considered
Micro Images

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Amniotic fluid embolism, uterine wall

Differential Diagnosis
  • Dilutional coagulopathy: may coexist with DIC
  • HELLP syndrome (H → hemolysis, EL → elevated liver enzymes, LP → low platelets)
    • Can also degenerate to DIC
  • Severe hepatic cirrhosis
  • TTP / HUS