Mechanisms of Action of Anesthetics for the Modulation of Perioperative Thrombosis: Evidence for Immune Mechanisms from Basic and Clinical Studies
Toshiharu Azma, Florin Tuluc, Taishin Ito, Chikako Aoyama-Mani, Shinji Kawahito and Hiroyuki Kinoshita
Affiliation: Department of Anesthesiology & Pain Medicine, Kohnodai Hospital, National Center for Global Health and Medicine, Kohnodai 1-7-1, Ichikawa, Chiba 272-8516, Japan.
Thrombotic events occurring in either arteries or veins are the primary causes of fatal perioperative cardiovascular events. Risk
factors for deep vein thrombosis, several of which are evidently associated with specific surgical procedures, are quite different from
those for arterial thrombosis (e.g., aging or atherosclerotic diseases). Thrombus formed in arteries consists mainly of platelets coated with
fibrin (i.e., white thrombus), while venous thrombus formed at relatively lower shear stress consists of all blood components including
erythrocytes as well as leukocytes infiltrated with fibrin (red thrombus). Clinical evidence indicates beneficial roles of neuraxial anesthesia/
analgesia in the prevention of VTE for patients undergoing high risk surgical procedures. To date, mechanisms of action of drugs used
for neuraxial anesthesia/analgesia to prevent venous thrombosis are uncertain. However, accumulation of clinical as well as experimental
findings points to the involvement of immune cells (especially monocytes) in red thrombus generation and to the interaction of anesthetics
with these cells. We also suggest that adhesion molecules associated with the formation of monocyte platelet aggregates as well as
substance P: neurokinin-1 receptor (SP/NK1R) pathway that involves neurogenic inflammation are crucial. Local anesthetics and NK1R
antagonists are candidate drugs that may possess the capability to prevent venous thrombotic disorders in perioperative settings.
Keywords: Perioperative thrombosis, neuraxial anesthesia/analgesia, substance P, neurokinin-1 receptor, microparticle, tissue factor, monocyte,
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