DIC

Question 1

Definition of disseminated intravascular coagulation (DIC)

Answer 1

• Disorder of hemostasis resulting from generation of excessive thrombin activity
• Frequently leads to bleeding (due to consumption of coagulation factors and activation of fibrinolysis system), thrombosis, and hemolytic anemia
• Usually due to too much TF in circulation
• Always a complication of another underlying disorder

Question 2

Pathogenesis of DIC

Answer 2

• Intrinsic system (activation of XII by endotoxins)
• Extrinsic system (activation of VII by TF/PL entering the circulation in massive amounts after trauma
• Common pathway (activation of X or prothrombin by snake venom)
• TF triggers almost all DIC
• DIC can be acute or chronic

Question 3

Lab manifestations of acute DIC

Answer 3

• Thrombocytopenia (precipitation of platelets due to thrombin activation)
• Hypofibrinogenemia, elevated circulating fibrin monomer due to conversion of fibrinogen to fibrin (causing a positive protamine sulfate test- soluble fibrin/fibrinogen complexes)
• Decreased levels of factors V, VIII, and XIII (thrombin activation then inactivation)
• Reduced levels of anticoagulants antithrombin, protein C/S (due to consumption or inactivation)
• Usually prolonged PT and aPTT
• Positive D-dimer test due to fibrin deposition followed by fibrinolysis (D-dimer mostly specific to activity of thrombin)

Question 4

Chronic DIC

Answer 4

• There may be normal levels of platelets, fibrinogen, coagulation factors
• Despite these being normal, bleeding can still occur
• Thrombosis is more common in chronic DIC than acute
• Thrombosis in chronic DIC are usually in major vessels, as opposed to acute DIC where thromboses are usually in the microcirculation

Question 5

Causes of DIC

Answer 5

• Infection (especially GN sepsis)
• Obstetrical conditions (most common is abrupt placenta, causing acute DIC)
• Neoplastic diseases (blast cells contain TF granules)
• Massive tissue necrosis (release of TF, especially in brain)
• Prolonged shock (hypotension leads to TF release)
• Misc (snake bites, purport fulminans)
• Localized: Kasabach-merritt (excess thrombin leads to hematoma), phlegmasia cerulean dolens (large amount of venous clotting), aortic aneurysm, transplant rejection

Question 6

Consequences of DIC

Answer 6

• Bleeding due to low platelets and coag factors (both increased consumption and fibrinolysis)
• Ischemic tissue damage (microthrombi)
• Stroke, MI due to thrombosis
• Fragmentation hemolytic anemia due to fibrin strands in microvasculature lysing the RBCs

Question 7

Management

Answer 7

• Remove underlying cause (most important)
• If bleeding is a problem then replace pt w/ cryo (fibrinogen and VII) and/or plasma for other coagulants (can use heparin in adjunctive Rx)
• If thrombosis/ischemia is a problem use heparin
• Heparin contraindicated if: cause of DIC is easily removed or short lived, no bleeding or thrombosis, bleeding is controlled w/ factor replacement alone

Question 8

Sources of TF in DIC

Answer 8

• Both monocytes/macrophages and endothelium are the major contributors to TF release
• Monos/macs release TF, ILs and TNF in response to endotoxin, Ag:Ab complexes, tumors
• Endothelium release TF in response to endotoxin, TNF and ILs

Question 9

DIC effects on coagulation

Answer 9

-Overall there is an increase in procoagulant activity and a decrease in anticoagulant activity (APC/S, antithrombin)