Relevance of hemolysis-induced tissue factor expression on monocytes in soft clot formation in alcohol-containing...

The fluidity of cadaveric blood is an important characteristic in the post-mortem examination of cases of asphyxial death. Although it is empirically known that soft blood clots are present in cadaveric blood containing alcohol, the relationship between such clots and blood alcohol is unclear. We addressed this issue through in vitro studies using blood collected from healthy volunteers. Assessment of global hemostasis by rotational thromboelastometry revealed that ethanol treatment enhanced the procoagulant activity of whole blood. However, ethanol inhibited epinephrine-induced platelet aggregation, whereas plasma levels of von Willebrand factor and the activity of coagulation factors VIII and IX were unaffected. In contrast, tissue factor (TF) activity was higher in plasma obtained from ethanol-treated whole blood than that in plasma from untreated blood. Ethanol induced hemolysis of red blood cells, and the consequent hemoglobin (Hb) release promoted de novo synthesis of TF in isolated monocytes, as determined by real-time reverse transcription PCR, western blotting, and flow cytometry. However, ethanol itself did not induce TF expression in monocytes. Given that TF activates the extrinsic coagulation pathway and amplifies hemostatic reactions, Hb-induced TF expression in monocytes might contribute to soft blood clot formation.