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DIC (Disseminated intravascular coagulation)

is characterized by excess thrombin generation with activation of the fibrinolytic system, which results in degradation of clotting factors and platelet membrane glycoproteins. Consumption of coagulation factors may occur in severe cases.

SX:
Typically, patients with DIC bleed from several sites and may experience spontaneous thrombotic manifestations.

Causes of DIC:
1. Events that initiate DIC:

• Massive tissue destruction:
  Burns, hemolytic transfusion reaction (usually ABO mismatch), tumor products, crush injury, complicated & extensive surgery, severe intracranial damage, retained conception products, placental abruption, amniotic fluid embolism, certain snake bites, acute promyelocytic leukemia.
  
• Extensive destruction of endothelial surfaces, exposure to foreign surfaces:
  Vasculitis (meningococcemia, Gram negative septicemia -is the most common cause of DIC), heatstroke, malignant hyperthermia, eclampsia, giant hemangiomas, immune complexes (?postvaricella purpura gangrenosa), certain snake bites.

2. Events that complicate & propagate DIC:  shock, complement pathway activation

Conditions Associated With Disseminated Intravascular Coagulation

• Infections: Gram-negative bacteremia,  Gram-positive bacteremia;
  Rocky Mountain spotted fever;  Typhoid fever
• Metabolic disorders:  Hypotension, Hypoxia, Hyper/hypothermia
• Obstetric complications: Abruptio placentae, Eclampsia, Amniotic fluid embolism, Retained dead fetus
• Tumors: Adenocarcinomas, Bulky lymphomas, tumor lysis syndrome, Acute promyelocytic, myelomonocytic, or monocytic leukemia
• Trauma: Crush injuries, Head injuries
• Toxins: Viper venom bites

Diagnosis:

• Smear of microangiopathic RBC - circulating schistocytes in up to 50%.
• Low platelet counts
• Prolonged Protime, PTT, & Thrombin time
• Low fibrinogen level
• Positive fibrin degradation product (FDP - Protamine test), also
• Positive fibrin D dimer test (not detected in primary fibrinolysis)

During DIC, plasmin is generated through the direct release of t-PA from perturbed or damaged endothelial cells. This is accompanied by plasminogen consumption, depletion of a2-antiplasmin (the specific inhibitor of plasmin), and the generation of circulating fibrinogen/fibrin degradation products (FDP and Fdp, respectively) and D-dimers from degraded cross-linked fibrin . Plasmin also inactivates factor VIII and degrades vWF.

TREATMENT OF DIC - is necessarily individualized
It is aimed primarily at the treatment of the underlying etiologic disease process and secondarily at the coagulopathy that results in the thrombotic and hemorrhagic manifestations.
In general, heparin is administered only for clinically significant DIC when the cause of the coagulopathy is ongoing; it is used as a stopgap measure while awaiting initiation of the benefits of definitive therapy (for example, induction chemotherapy for acute promyelocytic leukemia). Lower doses of heparin (50 U/kg bolus followed by continuous intravenous infusions at 400 to 750 U/h) are used to reduce hemorrhagic risks and should be adjusted appropriately to achieve increases in platelet counts and fibrinogen concentrations.

Very rarely, heparin resistance is encountered if AT-III levels are markedly decreased; in these circumstances, replenishment of AT-III levels with AT-III concentrates might be useful, although adequate prospective, controlled studies have not been conducted to confirm this premise.
Cryoprecipitate should be infused in severe hypofibrinogenemia to minimize potential bleeding, and
platelet transfusions are usually used to maintain counts greater than 20,000/µL or to reverse active thrombocytopenic bleeding complications. Both may be used in conjunction with low doses of heparin.
The use of antifibrinolytic agents such as e-aminocaproic acid or tranexamic acid is controversial because of their potential to exaggerate the thrombotic component of DIC by inhibiting fibrinolysis. However, their use in acute promyelocytic leukemia has been recommended to reduce bleeding complications associated with decreased levels of a2-antiplasmin.

REF:
ACP Library on Disk 2- (c) 1997 - American College of Physicians
E-Medicine   DIC  

DISSEMINATED INTRAVASCULAR COAGULATION
A primer for primary care physicians
PostgradMed March 2002

06092002