title: Hemodialysis patients have plasmatic hypercoagulability and decreased fibrinolytic vulnerability: role of carbon monoxide.
abstract: Chronic hemodialysis is associated with significant thrombophilia. Of interest, hemodialysis patients have increased carboxyhemoglobin (COHb) and exhaled carbon monoxide (CO), signs of upregulated heme oxygenase (Hmox) activity. Given that CO enhances plasmatic coagulation, we determined whether patients requiring chronic hemodialysis had an increase in endogenous CO, plasmatic hypercoagulability and decreased fibrinolytic vulnerability. Carbon monoxide was determined by noninvasive pulse oximetry measurement of COHb. Blood samples were obtained just before hemodialysis. Thrombelastographic methods to assess plasma coagulation kinetics, fibrinolytic kinetics, and formation of carboxyhemefibrinogen (COHF) were used. Hemodialysis patients (n = 45) had abnormally increased COHb concentrations of 2.2 ± 1.9%, indicative of Hmox upregulation. Coagulation and fibrinolytic parameter normal values were determined with normal individual (n = 30) plasma. Thirty-seven patients of the hemodialysis cohort had COHF formation (82.2%, [67.9%-92.0%]; mean, [95% confidence interval]), and many of this group of patients had abnormally great velocity of clot growth (73.3%, [58.1%-85.4%]) and strength (75.6%, [60.5%-87.1%]). Furthermore, over half of COHF positive patients had a hypofibrinolytic state, evidenced by an abnormally prolonged time to maximum rate of lysis (53.3%, [37.9%-68.6%]) and clot lysis time (64.4%, [48.8%-78.1%]). Carbon monoxide enhanced coagulation and diminished fibrinolytic vulnerability in hemodialysis patients. Future investigation of hemodialysis, CO-related thrombophilia is warranted.
authors.affiliation: From the *Department of Anesthesiology; and †Department of Medicine, University of Arizona College of Medicine, Tucson, Arizona.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Matika
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
authors.forename: Evangelina B
authors.initials: EB
authors.lastname: Steinbrenner
authors.forename: Amy N
authors.initials: AN
authors.lastname: Sussman
authors.forename: Machaiah
authors.initials: M
authors.lastname: Madhrira
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D002248:Carbon Monoxide / Q000097:blood*; D002263:Carboxyhemoglobin / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000031:analogs & derivatives / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*; D013916:Thrombelastography; D019851:Thrombophilia / Q000097:blood* / Q000209:etiology*; D055815:Young Adult
chemical_list: D002248:Carbon Monoxide; D005340:Fibrinogen; D002263:Carboxyhemoglobin