ABSTRACT
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.
KEYWORD
Disseminated intravascular coagulation - DIC - tissue factor - endothelium - thrombin
- tissue factor pathway inhibitor - TFPI
