The Role of the P2Y12 Receptor in Tissue Factor Induced Coagulation
Status:
Completed
Trial end date:
2010-11-01
Target enrollment:
Participant gender:
Summary
Severe sepsis still carries a high mortality rate despite advantages in intensive care
medicine and antimicrobial therapy. The inflammatory and procoagulant host response to
infection are intricately linked and interactions between platelets, leukocytes and the
endothelium play a central role in the pathogenesis of septic shock and disseminated
intravascular coagulation (DIC). Interestingly, one key player cell in coagulation, i.e. the
platelet, has been somewhat neglected as to its position in the pathogenesis of coagulation
abnormalities in sepsis. However, thienopyridines, irreversible platelet P2Y12 ADP-receptor
antagonists, e.g. prasugrel, could potentially provide beneficial anticoagulatory and
antiinflammatory effects: P2Y12 ADP-receptor antagonists reduce TF-induced coagulation
activation in various ex vivo and in vitro models. Moreover, various lines of evidence
indicate that thienopyridines may block platelet leukocyte interactions and thereby reduce
the propagation of the coagulation and inflammation process.
LPS-infusion in healthy volunteers provides a standardized model to safely study non overt
DIC and to document possible effects of therapeutic and prophylactic interventions.
The investigators hypothesize that thienopyridines, irreversible platelet P2Y12 ADP-receptor
antagonists, may blunt TF-triggered coagulation activation in humans, which will be studied
in a TF-dependent coagulation model in humans.