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2206 Part XII: Hemostasis and Thrombosis Chapter 129: Disseminated Intravascular Coagulation 2207

thrombelastography (TEG) over conventional coagulation assays is that hypotension, bleeding, and renal failure. Laboratory evidence of DIC
is provides an idea of platelet function as well as fibrinolytic activity. can accompany Korean, rift valley, and dengue-related hemorrhagic
Hyper- and hypocoagulability as demonstrated with TEG was shown fevers. 173–175 Release of TF from cells in which viruses replicate and
28
to correlate with clinically relevant morbidity and mortality in sev- increased levels of proinflammatory cytokines have been suggested as
eral studies, although its superiority over conventional tests has not mechanisms for initiation of the TF pathway in these conditions. 163
147
unequivocally been established. Even though there are no systematic
studies on the diagnostic accuracy of TEG for the diagnosis of DIC,
the test may be useful for assessing the global status of the coagulation PURPURA FULMINANS
system in critically ill patients. 148 Purpura fulminans is a severe, often lethal form of DIC in which
extensive areas of the skin over the extremities and buttocks undergo
hemorrhagic necrosis. The disease affects infants and children pre-
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SPECIFIC UNDERLYING DISORDERS dominantly, and occasionally adults. 177,178 Diffuse microthrombi in
small blood vessels, necrosis, and occasionally vasculitis are pres-
INFECTIOUS DISEASES ent in biopsies of skin lesions. Onset can be within 2 to 4 weeks of a
Bacterial infections are among the most common causes of DIC. 5,149 mild infection such as scarlet fever, varicella, or rubella, or can occur
Certain patients are particularly vulnerable to infection-induced DIC, during an acute viral or bacterial infection in patients with acquired
such as immune-compromised hosts, asplenic patients whose ability to or hereditary thrombophilias affecting the protein C inhibitory path-
clear bacteria, particularly pneumococci and meningococci, is impaired, way. 156,177 Homozygous protein C deficiency presents in neonates soon
and newborns whose coagulation inhibitory systems are immature. after birth as purpura fulminans, with or without extensive thrombo-
Infections are frequently superimposed on trauma and malignancies, sis. 179,180 Patients affected by purpura fulminans are acutely ill with fever,
which themselves are potential triggers of DIC. In addition, infections hypotension, and hemorrhage from multiple sites; they frequently have
177
can aggravate bleeding and thrombosis by directly inducing thrombo- typical laboratory signs of DIC. Excision of necrotic skin areas and
cytopenia, hepatic dysfunction, and shock associated with diminished grafting are indispensable at a later stage.
blood flow in the microcirculation. Clinically overt DIC may occur
150
in 30 to 50 percent of patients with Gram-negative sepsis. 151,152 DIC is
similarly common in patients with Gram-positive sepsis. 153,154 Extreme SOLID TUMORS
examples of sepsis-related DIC are (1) group A streptococcus toxic Trousseau was the first to describe the propensity to thrombosis of
shock syndrome, characterized by deep tissue infection, vascular col- patients with cancer and cachexia, and evidence for malignancy-related
lapse, vascular leakage, and multiorgan dysfunction; a streptococcal M primary fibrinolysis and/or DIC was provided 75 years ago. 9,181,182
protein forms complexes with fibrinogen, and these complexes bind to In 182 patients with malignant disorders, excessive bleeding was
β integrins of neutrophils leading to their activation ; and (2) menin- recorded in 75 cases, venous thrombosis in 123, migratory throm-
155
2
gococcemia, a fulminant Gram-negative infection characterized by bophlebitis in 96, arterial thrombosis in 45, and arterial embolism
extensive hemorrhagic necrosis, DIC, and shock. The extent of hemo- resulting from nonbacterial thrombotic endocarditis in 31. Multifocal
183
static derangement in patients with meningococcemia correlates with hemorrhagic infarctions of the brain, caused by fibrin microemboli and
prognosis. 156,157 More frequent Gram-negative infections associated manifested as disorders of consciousness, have been described. Patients
with DIC are caused by Pseudomonas aeruginosa, E. coli, and Proteus with solid tumors and DIC are more prone to thrombosis than to bleed-
vulgaris. Patients affected by such bacteremias may have only laboratory ing, whereas patients with leukemia and DIC are more prone to hemor-
signs of activated coagulation or may present with severe DIC, espe- rhage. The incidence of DIC in consecutive patients with solid tumors
cially when shock develops. 158,159 was 7 percent. 184
Severe secondary deficiency of a disintegrin-like metalloprotease Solid-tumor cells can express different procoagulant molecules
with thrombospondin type 1 repeats (ADAMTS13), the von Willebrand including TF, which forms a complex with factor VII(a) to activate fac-
cleaving protease, occurs in patients with sepsis-induced DIC and is tors IX and X, and a cancer procoagulant, a cysteine protease with factor
associated with a high incidence of acute renal failure. 160 X activating properties. 185,186 In breast cancer, TF is expressed by vascu-
Among the Gram-positive infections, Staphylococcus aureus lar endothelial cells as well as the tumor cells. 187,188 TF also appears to
bacteremia can cause DIC accompanied by renal cortical and dermal be involved in tumor metastasis and angiogenesis. 189–191 Cancer proco-
necrosis. The mechanism by which DIC is elicited may be related to agulant is an endopeptidase that can be found in extracts of neoplastic
an α-toxin that activates platelets and induces IL-1 secretion by mac- cells but also in the plasma of patients with solid tumors. 192,193 The exact
rophages. Streptococcus pneumoniae infection is associated with the role of cancer procoagulant in the pathogenesis of cancer-related DIC
161
Waterhouse-Friderichsen syndrome, particularly in asplenic patients. is unclear.
162
Initiation of DIC in these conditions is ascribed to the capsular antigen Interactions of P- and L-selectins with mucin from mucinous
of the bacterium and to antigen–antibody complex formation. Other adenocarcinoma can induce formation of platelet microthrombi and
163
Gram-positive bacteria that can cause DIC are the anaerobic clostridia. probably constitute a third mechanism of cancer-related thrombo-
Clostridial bacteremia is a highly lethal disease characterized by septic sis. Depending on the rate and quantity of exposure or influx of shed
194
shock, DIC, renal failure, and hemolytic anemia. 164 vesicles from tumors containing TF, a nonovert or overt DIC devel-
Activation of the coagulation system has also been documented ops. 39,195,196 For instance, a patient may be asymptomatic or present
for nonbacterial pathogens, that is, viruses (causing hemorrhagic with venous thromboembolism if the tumor cells expose or release TF
fevers), 164,165 protozoa (Malaria), 166,167 and fungi. Common viral slowly or intermittently and the ensuing utilization of fibrinogen and
168
infections, such as influenza, varicella, rubella, and rubeola, rarely are platelets is compensated by increased production of these components.
associated with DIC. However, purpura fulminans associated with Conversely, massive thrombosis or severe bleeding may supervene in a
169
DIC has been reported in patients with infections and either heredi- patient whose circulation is deluged by TF. 184,186
tary thrombophilias, 170,171 or acquired antibodies to protein S. Other Another mechanism by which tumor cells may contribute to the
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viral infections can cause “hemorrhagic fevers” characterized by fever, pathogenesis of DIC is by expressing fibrinolytic proteins. 197,198 Despite

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