Carbon monoxide: Anticoagulant or procoagulant?

Abstract

Within the past decade there have been several investigations attempting to define the impact of exogenous and endogenous carbon monoxide exposure on hemostasis.Critically, two bodies of literature have emerged, with carbon monoxide mediated platelet inhibition cited as a cause of in vitro human and in vitro/in vivo rodent anticoagulation. In contrast, interaction with heme groups associated with fibrinogen, α 2 -antiplasmin and plasmin by carbon monoxide has resulted in enhanced coagulation and decreased fibrinolysis in vitro in human and other species, and in vivo in rabbits. Of interest, the ultrastructure of platelet rich plasma thrombi demonstrates an abnormal increase in fine fiber formation and matting that are obtained from humans exposed to carbon monoxide.Further, thrombi obtained from humans and rabbits have very similar ultrastructures, whereas mice and rats have more fine fibers and matting present. In sum, there may be

HO-1/CO system in tumor growth, angiogenesis and metabolism — Targeting HO-1 as an anti-tumor therapy

“…This has to be considered in the light of studies indicating that CO can rather potentiate and not inhibit blood coagulation. In accordance this may correlate with the COHb level in patients with various cancers [100]. However, overexpression of HO-1 in A549 NSCLC adenocarcinoma cells inhibited their proliferation [104], although the similar effect has been obtained by silencing of Nrf2 in the same cells [105].…”

Protective role of hemeoxygenase-1 in gastrointestinal diseases

“…For instance free heme can activate the inflammatory cascade [151] and biliverdin/bilirubin and CO can be toxic at high levels in tissues. Biliverdin which is rapidly converted to bilirubin is neurotoxic in newborns resulting in kernicterus [152] and CO can affect hemostasis by having both anticoagulant and procoagulant functions [153]. Thus CO potential effects on coagulation is an important consideration for gastrointestinal diseases that are associated with vascular complication; for example venous or arterial thromboembolism are both well-recognized extraintestinal complications in IBD [154].…”

Gasomediators (·NO, CO, and H2S) and their role in hemostasis and thrombosis

“…Other studies indicate that nitric oxide can rapidly react with the isolated from humans and other mammalian species (rabbits, mice and 302 rats) [89]. It is interesting to note that the ultrastructure of platelet-rich 303 plasma thrombi obtained from humans exposed to CO demonstrates an 304 abnormal fine fiber formation and matting.…”

“…It is interesting to note that the ultrastructure of platelet-rich 303 plasma thrombi obtained from humans exposed to CO demonstrates an 304 abnormal fine fiber formation and matting. Furthermore, although 305 thrombi obtained from humans and rabbits demonstrate a similar ultra-306 structure, rats and mice have more fine fibers and matting present [89].…”

“…A recent study by Nielsen and Pretorius [89] notes that CO-releasing as well as the therapeutic potential of CORMs, has been provided by 332 Nielsen and Pretorius [89]. process, particularly its beneficial properties, are given by Olas [110].…”