Sepsis almost invariably leads to
hemostatic abnormalities, ranging from insignificant laboratory changes to severe
disseminated intravascular coagulation (
DIC). There is compelling evidence from clinical and experimental studies that
DIC is involved in the pathogenesis of microvascular dysfunction and contributes to organ failure. In addition, the massive and ongoing activation of coagulation, may deplete platelets and
coagulation factors, which may in turn cause
bleeding. Recent insights into important pathogenetic mechanisms that may lead to
DIC have resulted in novel preventive and therapeutic approaches to patients with
sepsis and a derangement of coagulation.
Thrombin generation proceeds via the (extrinsic)
tissue factor/
factor VIIa route and simultaneously occurring depression of inhibitory mechanisms, such as
antithrombin III and the
protein C system. Also, impaired
fibrin degradation, due to high circulating levels of
PAI-1, contributes to enhanced intravascular
fibrin deposition. Supportive strategies aimed at the inhibition of coagulation activation may be justified on theoretical grounds and have been found to be beneficial in experimental and initial clinical studies. These strategies comprise inhibition of
tissue factor-mediated activation of coagulation or restoration of physiological
anticoagulant pathways, by means of the administration of
antithrombin concentrate or recombinant human activated
protein C.