title: Plasmatic hypercoagulation in patients with breast cancer: role of heme oxygenase-1.
abstract: Breast cancer is an important health threat to women worldwide, and is associated with a 9-14% incidence of thrombophilia. Of interest, patients with breast cancer have been noted to have an increase in endogenous carbon monoxide production via upregulation of heme oxygenase-1 activity. Given that it has been demonstrated that carbon monoxide enhances plasmatic coagulation in vitro and in vivo, we sought to determine whether patients with breast cancer had an increase in endogenous carbon monoxide and concurrent plasmatic hypercoagulability. Breast cancer patients who were not smokers scheduled to undergo partial or complete mastectomy (n = 18) had 15 ml of whole blood collected via an indwelling intravenous catheter and anticoagulated with sodium citrate. Whole blood was centrifuged and citrated plasma assessed with a thromboelastometric method to measure coagulation kinetics and the formation of carboxyhemefibrinogen. Breast cancer patients were determined to have an abnormally increased carboxyhemoglobin concentration of 2.5 ± 1.3%, indicative of heme oxygenase-1 upregulation. Breast cancer patient plasma on average clotted 73% more quickly and had 32% stronger thrombus strength than normal individual (n = 30) plasma. Further, 44% of breast cancer patients had plasma clot strength that exceeded the 95% confidence interval value observed in normal individuals, and 75% of this hypercoagulable subgroup had carboxyhemefibrinogen formation. Future investigation of the role played by heme oxygenase-1-derived carbon monoxide in the pathogenesis of breast cancer-related thrombophilia is warranted.
authors.affiliation: aThe Department of Anesthesiology bThe Department of Surgery, The University of Arizona College of Medicine, Tucson, Arizona, USA.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
authors.forename: Michele L B
authors.initials: ML
authors.lastname: Ley
authors.forename: Amy L
authors.initials: AL
authors.lastname: Waer
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Alger
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Matika
authors.forename: Evangelina B
authors.initials: EB
authors.lastname: Steinbrenner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001780:Blood Coagulation Tests; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery / Q000628:therapy; D002248:Carbon Monoxide / Q000378:metabolism; D002263:Carboxyhemoglobin / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000473:pathology / Q000601:surgery / Q000628:therapy; D018275:Carcinoma, Lobular / Q000201:enzymology* / Q000473:pathology / Q000601:surgery / Q000628:therapy; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015409:Mastectomy, Radical; D015412:Mastectomy, Segmental; D008875:Middle Aged; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D002248:Carbon Monoxide; D005340:Fibrinogen; D002263:Carboxyhemoglobin; D051547:Heme Oxygenase-1