In a severely ill patient, the sudden occurrence of bleeding from a venipuncture or incision site, gastrointestinal or pulmonary hemorrhage, petechiae, or ecchymosis or evidence of periph-V
T: AT III Fibrin eral gangrene or thrombosis suggests the diagnosis of DIC.
Treatment. The treatment of DIC is challenging. General guidelines include the following: treat the disorder inducing the DIC first; support the patient by correcting hypoxia, acidosis, and poor perfusion; and replace depleted blood-clotting factors, platelets, and anticoagulant proteins by transfusion.
Heparin may be used to treat significant arterial or venous thrombotic disease unless sites of life-threatening bleeding coexist.
Etiology. A hereditary predisposition to thrombosis (see Table 151-1) may be caused by a deficiency of an anticoagulant protein (protein C or S, antithrombin, or plasminogen) (Fig. 151-5), by an abnormality of a procoagulant protein making it resistant to proteolysis by its respective inhibitor (factor 5 Leiden), by a mutation resulting in an increased level of a procoagulant protein (prothrombin 20210), or by damage to endothelial cells (homocysteinemia). Neonates with deficiency syndromes may be particularly vulnerable to thrombosis. Neonates with homozygous protein C deficiency present with purpura fulminans or thrombosis of the major arteries and veins or both. Many individuals with an inherited predisposition to thrombosis exhibit symptoms in adolescence or early adulthood. Protein C deficiency presenting in adulthood usually is inherited as an autosomal dominant trait, whereas the homozygous form usually is autosomal recessive. Protein S and antithrombin III deficiencies are inherited as autosomal dominant traits. Factor 5 Leiden is the most common hereditary cause of a predisposition to thrombosis, appearing in 3% to 5% of whites. Acquired antiphospholipid antibodies (anticardiolipin and lupus anticoagulant) also predispose to thrombosis.
Clinical Manifestations. Neonates and adolescents are the most likely pediatric patients to present with thromboembolic disease. Indwelling catheters, vasculitis, sepsis, immobilization, nephrotic syndrome, coagulopathy, trauma, infection, surgery, inflammatory bowel disease, oral contraceptive agents, pregnancy, and abortion all predispose to thrombosis.
Figure 151-5 Formation of the hemostatic plug at the site of vascular injury. Three major physiologic anticoagulant mechanisms— antithrombin III (AT III), protein C, and the fibrinolytic system—are activated to limit clot formation to the site of damage and to prevent generalized thrombosis. T, Thrombin. (From Schafer A: The hypercoagulable state, Ann Intern Med 102:814–828, 1985.)
The manifestations of pulmonary emboli vary from no findings to chest pain, diminished breath sounds, a loud S2, cyanosis, tachypnea, and hypoxemia.
Diagnostic and Imaging Studies. Venous thrombosis can be detected noninvasively by ultrasound Doppler flow compression studies. The gold standard for diagnosis is the venogram. An abnormal (high probability) ventilation-perfusion scan or detection of an intravascular thrombus on helical computed tomography (CT) is diagnostic of pulmonary emboli. There are no appropriate screening studies for thrombotic disorders. Diagnosis of a congenital or acquired predisposition to thrombosis requires a battery of specific assays.