title: D-dimer predicts major bleeding, cardiovascular events and all-cause mortality during warfarin treatment.
abstract: OBJECTIVE
  Previous studies have shown that biomarkers in blood plasma can predict bleeding complications during anticoagulant treatment as well as thromboembolic events and may improve existing risk stratification schemes in patients on or considered for oral anticoagulant treatment. The aim of this study was to investigate if levels of d-dimer, tissue plasminogen activator (tPA) and its complex with plasminogen inhibitor type 1 (tPA/PAI-1 complex) can predict major bleedings, cardiovascular events and all-cause mortality in patients with warfarin treatment.
  
  
  METHODS
  In a longitudinal cohort study, 719 patients on oral anticoagulant treatment were followed for a total of 3001 treatment years. Major bleeding, stroke, arterial emboli, myocardial infarction and death were recorded and classified. Blood samples collected at baseline were analyzed for d-dimer, tPA, and tPA/PAI-1 complex.
  
  
  RESULTS
  In multivariate Cox regression analysis, high levels of d-dimer were associated with major bleeding (HR 1.27 per SD; 95% CI: 1.01-1.60), cardiovascular events (HR 1.23 per SD; 95% CI: 1.05-1.45) and all-cause mortality (HR 1.25 per SD; 95% CI: 1.06-1.47). Neither tPA nor the tPA/PAI-1 complex was associated with major bleeding, cardiovascular events or all-cause mortality.
  
  
  CONCLUSIONS
  We conclude that high levels of d-dimer predict major bleeding, cardiovascular events and all-cause mortality during warfarin treatment.
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. Electronic address: Marcus.lind@vll.se.
authors.forename: Marcus
authors.initials: M
authors.lastname: Lind
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Kurt
authors.initials: K
authors.lastname: Boman
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Johansson
authors.affiliation: Department of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
authors.forename: Torbjörn K
authors.initials: TK
authors.lastname: Nilsson
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Lisbeth Slunga
authors.initials: LS
authors.lastname: Järvholm
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Jan-Håkan
authors.initials: JH
authors.lastname: Jansson
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006470:Hemorrhage / Q000139:chemically induced* / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D016016:Proportional Hazards Models; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; C036309:fibrin fragment D; D014859:Warfarin
keywords: Bleeding; Cardiovascular events; Mortality; PAI-1; Warfarin; d-dimer