The tissue factor pathway in disseminated intravascular coagulation.
In most instances, tissue factor (TF) exposed to the circulation is the sole culprit underlying the initiation of disseminated intravascular coagulation (DIC), although notable exceptions because of a more direct activation of the coagulation system, by snake venoms, for example, do occur. Peripheral monocytes and subendothelial structures are the potential sources of such TF; in the former, TF emerges on the cell surface on synthesis induction and in the latter it becomes available subsequent to permeability changes or damage to the endothelium. Subendothelial TF is constitutively present in fibroblasts, pericytes, and macrophages and at a higher than normal level in tumor-associated macrophages. This scenario of coagulation activation probably describes the principal events underlying emerging acute DIC states under pathophysiological conditions such as abruptio placentae, septic abortion, amniotic fluid embolization, and pregnancy toxemia. Under disease conditions associated with DIC, the continuous exposure to excess TF typically exhausts the available tissue factor pathway inhibitor (TFPI), leading to rampant thrombin generation, persistent feedback activation of factor XI (FXI) by the generated thrombin, and hence virtually uncheckable ongoing fibrin generation (DIC). Recently, it was shown that patients subject to meningococcal sepsis had comparatively large amounts of mainly monocyte-derived circulating TF-containing microparticles. Because phosphatidylserine (PS) is exposed on such particles, in addition to TF, they probably contribute crucially to DIC during meningococcal sepsis. Although endothelial cells (EC) have been shown to express large amounts of TF in vitro, this observation hardly relates to the situation in vivo, where, in contrast, synthesis and exposure of EC TF is very limited and not likely to be of any significance in emerging and ongoing DIC.
Østerud
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Department of Biochemistry, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Tromsø, Norway. Bjarne.Osterud@fagmed.uit.no
Bjørklid
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D000818:Animals; D001777:Blood Coagulation; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D011247:Pregnancy; D015398:Signal Transduction; D013925:Thromboplastin / Q000502:physiology*
D013925:Thromboplastin