Etiology

Any life-threatening severe systemic disease associated with hypoxia, acidosis, tissue necrosis, shock, and/or endothelial damage may trigger DIC. A large number of conditions have been reported to be associated with DIC (Table 477-1). Although the clinical symptoms are more often hemorrhagic, the initiating event is usually excessive activation of clotting that consumes both the physiologic anticoagulants (protein C, protein S, and antithrombin III) and procoagulants, resulting in a deficiency of factor V, factor VIII, prothrombin, fibrinogen, and platelets. Commonly, the clinical result of this sequence of events is hemorrhage. The hemostatic dysregulation may also result in thromboses in the skin, kidneys, and other organs. Better understanding of the pathophysiology of hemostasis has lead to an appreciation of the critical interaction of the coagulation pathways with the innate immune system and inflammatory response that likely contributes to the widespread dysregulation present in DIC.

Clinical Manifestations

DIC accompanies a severe systemic disease process, usually with shock. Bleeding frequently first occurs from sites of venipuncture or surgical incision. The skin may show petechiae and ecchymoses. Tissue necrosis may involve many organs and can be most spectacularly seen as infarction of large areas of skin, subcutaneous tissue, or kidneys. Anemia caused by hemolysis may develop rapidly, owing to microangiopathic hemolytic anemia.

Laboratory Findings

There is no well-defined sequence of events. Certain coagulation factors (factors II, V, and VIII, and fibrinogen) and platelets may be consumed by the ongoing intravascular clotting process, with resultant prolongation of the prothrombin, partial thromboplastin, and thrombin times. Platelet counts may be profoundly depressed. The blood smear may contain fragmented and burr- and helmet-shaped red blood cells (schistocytes). In addition, because the fibrinolytic mechanism is activated, fibrinogen degradation products (FDPs, D-dimers) appear in the blood. The D-dimer is formed by fibrinolysis of a cross-linked fibrin clot. The D-dimer assay is as sensitive as the FDP test and more specific for activation of coagulation and fibrinolysis.

Treatment

The 1st 2 steps in the treatment of DIC are the most critical: (1) treat the trigger that caused DIC and (2) restore normal homeostasis by correcting the shock, acidosis, and hypoxia that usually complicate DIC. If the underlying problem can be controlled and the patient stabilized, bleeding quickly ceases, and there is improvement of the abnormal laboratory findings. Blood components are used for replacement therapy in patients with hemorrhage and may consist of platelet infusions (for thrombocytopenia), cryoprecipitate (for hypofibrinogenemia), and/or fresh frozen plasma (for replacement of other coagulation factors and natural inhibitors).

In DIC associated with sepsis, a controlled trial of drotrecogin alpha (activated protein C concentrate [APC]) in adults with sepsis showed a statistically significant survival advantage in those treated with APC. Clinical trials using protein C concentrate in purpura fulminans and APC in children with sepsis syndrome have not shown a statistically significant improvement.

The role of heparin in DIC is limited to patients who have vascular thrombosis in association with DIC or who require prophylaxis because they are at high risk for venous thromboembolism. Such individuals should be treated as outlined in Chapter 473.1, with careful attention to replacement therapy to maintain an adequate platelet count and thus limit bleeding complications.

The prognosis of patients with DIC is primarily dependent on the outcome of the treatment of the primary disease and prevention of end-organ damage.