The most common abnormality of hemostasis in the critically ill patient is DIC. This is an acquired condition which is commonly associated with sepsis, extensive surgery, hemorrhage, acute cardiovascular insult, malignancy, and obstetric complications. The clinical consequences of DIC are a potentially devastating consumptive thrombohemorrhagic disorder. Recent advances suggest a key role for cytokines such as tumor necrosis factor and interleukin 1 (IL-1) in the pathogenesis of DIC. These cytokines are expressed very early following an acute insult and have the ability to influence a variety of cellular processes. Two hemostatic pathways appear to be particularly prone to modulation by these cytokines. One is the tissue-factor-mediated pathway of coagulation. Because tissue factor is a potent initiator of coagulation, its expression is highly regulated. It is constitutively expressed in cells corresponding to biological boundary layers such as the skin epidermis, adventitia around blood vessels, mucosal epithelium lining the gut, and capsules surrounding organs. Thus tissue factor forms a 'hemostatic envelope' encasing blood vessels, organ structures, and the entire organism. Cells which are normally in direct contact with blood (e.g. leukocytes) do not express tissue factor. However, in vitro studies show that monocytes and endothelial cells can express tissue factor following exposure to bacterial endotoxins, tumor necrosis factor, IL-1, activated complement, and immune complexes. These inflammatory mediators further exacerbate the procoagulant state by downregulating thrombomodulin expression on the endothelium, thereby inactivating the protein C anticoagulant pathway. Such a procoagulant state is likely to overwhelm other control mechanisms and is believed to be the basis of DIC. There are in vivo data to support this theory. Monocytes recovered from the blood and other anatomical sites (e.g. peritoneum) of rabbits treated with endotoxin express strong tissue factor activity. In baboons, injection of endotoxins results in fatal DIC which can be ameliorated by prior infusion of an anti-tissue-factor antibody. Specific blockers of tumor necrosis factor and IL-1 also diminish mortality in experimental endotoxic shock models. In humans, elevation of monocyte tissue factor expression is associated with septicemia, malignancies, and obstructive jaundice; these are all conditions with a high incidence of DIC. Patients suffering from meningococcal septicemia have an acquired protein C deficiency. The prognosis in these patients is generally poor, but infusion of protein C concentrates has led to a rapid perceived improvement in the patient's condition. Another mechanism which downregulates the protein C pathway is related to the fact that protein S forms a reversible inactive complex with C4b binding protein. C4b binding protein is an acute phase reactant whose levels increase during inflammation resulting in a decrease in active protein S.
The laboratory abnormalities found in DIC and other disorders commonly seen in the intensive care unit are summarized in Table.!. Bibliography
Mannucci, P.M. and Giangrande, P.L.F. (1994). Acquired disorders of coagulation. In Haemostasis and thrombosis, Vol. 2 (ed. A.L. Bloom, C.D. Forbes, D.P. Thomas, and E.G.D. Tuddenham), pp. 949-68. Churchill Livingstone, Edinburgh.
Staudinger, T., Locker, G.J., and Frass, M. (1996). Management of acquired coagulation disorders in emergency and intensive care medicine. Seminars in Thrombosis and Hemostasis, 22, 93-104.
10.2.2 Disseminated intravascular coagulation
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