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Coagulation

Acquired bleeding disorders

Disseminated intravascular coagulation (DIC)


Reviewers: Kendall Crookston, M.D., Ph.D., University of New Mexico; Lizabeth Rosenbaum, M.D., University of New Mexico; Julie Gober-Wilcox, M.D., Resident, University of New Mexico (see Reviewers page)
Revised: 17 August 2010, last major update August 2010
Copyright: (c) 2006-2010, PathologyOutlines.com, Inc.

Definition and pathophysiology
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● 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
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Key events in DIC

Epidemiology
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● 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
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● 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
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● 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
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● 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+ Castlemanís 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
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● 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
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● 30 year old woman with DIC due to amniotic fluid embolism (Arch Pathol Lab Med 2002;126:869)

Treatment
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● 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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Schistocyte

Amniotic fluid embolism - uterine wall - figure 1: amniotic fluid debris; figure 2: lanugo hair

Differential diagnosis
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● Severe hepatic cirrhosis
● Dilutional coagulopathy (but may coexist with DIC)
● HELLP syndrome (H-hemolysis; EL-elevated liver enzymes; LP-low platelets); can also degenerate to DIC
● TTP/HUS

End of Coagulation > Acquired bleeding disorders > Disseminated intravascular coagulation (DIC)


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