The tissue factor pathway in disseminated intravascular coagulation

Area of Science:

• Hematology
• Pathophysiology

Background:

• Tissue factor (TF) is the primary initiator of disseminated intravascular coagulation (DIC) in most cases.
• TF originates from peripheral monocytes and subendothelial structures, becoming accessible through cell activation or endothelial damage.
• Elevated TF levels are observed in conditions like abruptio placentae, sepsis, and pregnancy toxemia.

Purpose of the Study:

• To elucidate the role of tissue factor (TF) in the initiation and perpetuation of disseminated intravascular coagulation (DIC).
• To investigate the sources and mechanisms of TF exposure in various pathophysiological states.
• To understand the contribution of TF-containing microparticles in DIC, particularly in meningococcal sepsis.

Main Methods:

• Review of existing literature on TF, coagulation, and DIC.
• Analysis of TF expression in monocytes and subendothelial cells.
• Examination of TF-containing microparticles in meningococcal sepsis.

Main Results:

• TF exposure from monocytes and subendothelial sources drives DIC initiation and progression.
• Excessive TF overwhelms tissue factor pathway inhibitor (TFPI), causing uncontrolled thrombin and fibrin generation.
• Monocyte-derived TF-containing microparticles, exposing phosphatidylserine, are implicated in DIC during meningococcal sepsis.
• Endothelial cell TF expression in vivo is limited and unlikely to significantly contribute to DIC.

Conclusions:

• TF is the central mediator in the pathogenesis of DIC.
• Understanding TF sources and regulation is crucial for managing DIC.
• TF-bearing microparticles represent a significant procoagulant factor in specific DIC contexts.