title: Derangement of hemostasis in rheumatoid arthritis: association with demographic, inflammatory and metabolic factors.
abstract: Disturbance of fibrinolysis is common in rheumatoid arthritis (RA), and it may be associated with the increased cardiovascular risk observed in this population. We aimed to assess coagulation derangement and investigate whether abnormalities are influenced by demographic, inflammatory or metabolic factors in patients with RA. Levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), fibrinogen, prothrombin fragment 1 + 2 (PF1 + 2), thrombomodulin (TM), protein C and Von Willebrand factor (vWF) were compared between 141 RA patients and 50 healthy hospital controls. Within RA, coagulation factors were assessed alongside several demographic, inflammation and metabolic indicators. RA patients had higher levels of coagulation factors than controls. After correction for age and sex, having RA predicted increased tPA (B = 0.15, P < 0.001), PAI-1 (B = 0.21, P < 0.001), fibrinogen (B = 0.86, P < 0.001), PF1 + 2 (B = 0.20, P < 0.001), and TM (B = 0.01, P = 0.03) levels. CRP correlated positively with tPA (P < 0.05), fibrinogen (P < 0.001), TM (P < 0.05), PF1 + 2 (P < 0.001) and vWF (P < 0.001). Metabolic factors linked with coagulation factors were hypertriglyceridaemia (tPA, P < 0.05; PAI-1, P < 0.05; protein C, P < 0.05) and insulin resistance (tPA, P < 0.01; PAI-1, P < 0.01; vWF, P < 0.05). Imbalance of coagulation and fibrinolytic mechanisms is common in RA and associates with age, inflammation, and metabolic factors. Further studies may determine whether these abnormalities are the consequence of acute inflammation or markers of vascular dysfunction.
authors.affiliation: Department of Rheumatology, Dudley Group of Hospitals, NHS FT, Dudley, West Midlands, DY1 2HQ, UK. dimitroul@hotmail.com
authors.forename: Theodoros
authors.initials: T
authors.lastname: Dimitroulas
authors.forename: Karen M J
authors.initials: KM
authors.lastname: Douglas
authors.forename: Vasileios F
authors.initials: VF
authors.lastname: Panoulas
authors.forename: Tracey
authors.initials: T
authors.lastname: Toms
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Smith
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Treharne
authors.forename: Peter
authors.initials: P
authors.lastname: Nightingale
authors.forename: James
authors.initials: J
authors.lastname: Hodson
authors.forename: George D
authors.initials: GD
authors.lastname: Kitas
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000503:physiopathology; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000150:complications; D003430:Cross-Sectional Studies; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011486:Protein C / Q000378:metabolism; D011516:Prothrombin; D012044:Regression Analysis; D012307:Risk Factors; D018180:Thrombomodulin / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; C051321:SERPINE1 protein, human; D018180:Thrombomodulin; C045879:prothrombin fragment 1.2; D014841:von Willebrand Factor; D011516:Prothrombin; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator