DIC can be either an explosive and life-threatening bleeding disorder or a relatively mild or subclinical disorder. Although a long list of diseases can be complicated by DIC, it is most frequently associated with obstetric catastrophes, metastatic malignancy, massive trauma, and bacterial sepsis (Table 102-1). Tentative triggering mechanisms have been identified. Tumors and traumatized or necrotic tissue release tissue factor into the circulation. Endotoxin from gram-negative bacteria activates several steps in the coagulation cascade. In addition to a direct effect on the activation of Hageman factor (factor XII), endotoxin induces the expression of tissue factor on the surface of monocytes and endothelial cells. These activated cell surfaces then accelerate coagulation reactions. These potent thrombogenic stimuli cause the deposition of small thrombi and emboli throughout the microvasculature. This early thrombotic phase of DIC is then followed by a phase of procoagulant consumption and secondary fibrinolysis. Continued fibrin formation and fibrinolysis lead to hemorrhage from the coagulation factor and platelet depletion and the antihemostatic effects of fibrin degradation products (Fig. 102-2).

View Figure

FIGURE 102-2 The pathophysiology of disseminated intravascular coagulation (DIC). Shown are the interactions between coagulation and fibrinolytic pathways that result in bleeding in patients with DIC.

TABLE 102-1 Etiologic Factors and Disorders Causing Disseminated Intravascular Coagulation
________________________________________
Liberation of tissue factors Obstetric syndromes—abruptio placentae, amniotic fluid embolism, retained dead fetus, second trimester abortion
Hemolysis
Neoplasms, particularly mucinous adenocarcinomas, acute promyelocytic leukemia
Intravascular hemolysis
Fat embolism
Tissue damage—burns, frostbite, head injury, gunshot wounds
Endothelial damage Aortic aneurysm
Hemolytic uremic syndrome
Acute glomerulonephritis
Rocky Mountain spotted fever
Vascular malformation, decreased blood flow Kasabach-Merritt syndrome
Infections Bacterial: staphylococci, streptococci, pneumococci, meningococci, gram-negative bacilli
Viral: arboviruses, varicella, variola, rubella
Parasitic: malaria, kala-azar
Rickettsial: Rocky Mountain spotted fever
Mycotic: acute histoplasmosis
________________________________________
Source: Modified from RI Handin, RD Rosenberg, in Hematology, 4th ed, WS Beck (ed), Cambridge, MA, MIT Press, 1985.

The clinical presentation varies with the stage and severity of the
P.684

syndrome. Most patients have extensive skin and mucous membrane bleeding and hemorrhage from surgical incisions or venipuncture or catheter sites. Less often, patients present with peripheral acrocyanosis, thrombosis, and pregangrenous changes in digits, genitalia, and nose—areas where blood flow is markedly reduced by vasospasm or microthrombi. Some patients, particularly those with chronic DIC and malignancy, have laboratory abnormalities without any evidence of thrombosis or hemorrhage.
The laboratory manifestations include thrombocytopenia and the presence of schistocytes or fragmented red blood cells that arise from cell trapping and damage within fibrin thrombi; prolonged PT and PTT and thrombin time and a reduced fibrinogen level from depletion of coagulation proteins; and elevated fibrin degradation products (FDP) from intense secondary fibrinolysis. The D dimer immunoassay, which measures cross-linked fibrin derivatives (i.e., those that have been in blood clots), is a more specific FDP assay. Low fibrinogen levels in DIC predict more bleeding.
TREATMENT
DIC, although sometimes indolent, can cause life-threatening hemorrhage and may require emergency treatment including (1) an attempt to correct any reversible cause of DIC; (2) measures to control the major symptom, either bleeding or thrombosis; and (3) a prophylactic regimen to prevent recurrence in cases of chronic DIC. Treatment will vary with the clinical presentation. In patients with an obstetric complication such as abruptio placentae or acute bacterial sepsis, prompt delivery of the fetus and placenta or treatment with appropriate antibiotics will reverse the DIC syndrome. In patients with metastatic tumor causing DIC, control of the primary disease may not be possible, and long-term prophylaxis may be necessary.
Patients with bleeding as a major symptom should receive fresh-frozen plasma to replace depleted clotting factors and platelet concentrates to correct thrombocytopenia. Those with acrocyanosis and incipient gangrene or other thrombotic problems need immediate anticoagulation with intravenous heparin. The use of heparin in the treatment of bleeding is still controversial. Although it is a logical way to reduce thrombin generation and prevent further consumption of clotting proteins, it should be reserved for patients with thrombosis or who continue to bleed despite vigorous treatment with plasma and platelets.
Patients who initially have mild asymptomatic DIC may begin to bleed following surgery or chemotherapy. For example, mild DIC, without clinical bleeding, has been documented during saline- or prostaglandin-induced midtrimester abortions. Prophylactic treatment of patients with heparin may prevent progression of a mild DIC syndrome and has been used in the treatment of patients with acute promyelocytic leukemia and in some patients with a retained dead fetus who require surgical extraction. However, most patients with low-grade DIC can be managed with plasma and platelet replacement and do not require heparin. Chronic DIC does not respond to oral warfarin anticoagulants, but it can be controlled with long-term heparin infusion. Occasional patients with indolent tumors and severe DIC have been maintained on heparin administered by intermittent subcutaneous injection or continuous infusion with portable pumps.
Despite our detailed understanding of the pathophysiology of DIC and a vigorous approach to therapy, treatment does not usually change the natural history of the underlying disorder. Therapy will only stabilize the patient, prevent exsanguination or massive thrombosis, and permit institution of definitive therapy.