title: The influence of corticosteroids on hemostasis in healthy subjects.
abstract: BACKGROUND
  Corticosteroids have been associated with an increased risk of venous thromboembolism in patients treated for inflammatory diseases. It is unclear whether the thrombotic risk is induced by the inflammation of the underlying inflammatory diseases or whether corticosteroids are prothrombotic as well. Considering the widespread use of corticosteroids in clinical practise, it is critical to know whether corticosteroids enhance coagulation.
  
  
  OBJECTIVE
  To investigate whether a 10-day prednisolone burst therapy activates hemostasis in healthy individuals.
  
  
  METHODS
  Healthy subjects received either 0.5 mg kg(-1) day(-1) of oral prednisolone or placebo. Venous blood was collected at baseline, day 1 and day 10 and tested for thrombin-antithrombin complexes (TATc), D-dimer, plasmin-alpha2-antiplasmin complexes (PAPc), plasminogen-activator inhibitor type-1 (PAI-1), von Willebrand factor (VWF) and thrombin generation (peak thrombin, velocity index and endogenous thrombin potential [ETP]).
  
  
  RESULTS
  Fifteen subjects received prednisolone and 16 placebo (median age 29 vs. 22 years, female subjects 33% vs. 56%, respectively). Peak thrombin and velocity index were higher in the placebo group at baseline. After 10 days of treatment, peak thrombin, velocity index, PAI-1 and VWF increased in the oral prednisolone group as compared with the placebo group (15.8 [SD 16.3] vs. -0.1 [SD 16.1], 41.2 [SD 41.3] vs. -2.3 [SD 42.7], 18.0 [IQR 8.0-37.0] vs. 0.5 [IQR -18.5-13.0], 4.0 [IQR -1.0-12.0] vs. 0.0 [IQR -2.5-1.5], respectively). No changes were observed for TATc, ETP, PAPc and D-dimer.
  
  
  CONCLUSIONS
  Oral prednisolone induces a procoagulant state in healthy subjects, suggesting that corticosteroid treatment may increase the thromboembolic risk in patients with inflammatory diseases.
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: Majoor
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: M M S
authors.initials: MM
authors.lastname: Sneeboer
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: de Kievit
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.|Department of Plasma Proteins, Sanquin Research, Amsterdam, the Netherlands.
authors.forename: J C M
authors.identifier: http://orcid.org/0000-0002-4198-6780
authors.initials: JC
authors.lastname: Meijers
authors.affiliation: Center of Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, Amsterdam, the Netherlands.|Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Lutter
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: E H
authors.initials: EH
authors.lastname: Bel
authors.affiliation: Department of Vascular Medicine, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: P W
authors.initials: PW
authors.lastname: Kamphuisen
mesh_terms: D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000009:adverse effects*; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry; D005342:Fibrinolysis / Q000187:drug effects; D064368:Healthy Volunteers; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000150:complications; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011239:Prednisolone / Q000009:adverse effects*; D013917:Thrombin / Q000737:chemistry; D054556:Venous Thromboembolism / Q000139:chemically induced; D055815:Young Adult; D014841:von Willebrand Factor / Q000737:chemistry
chemical_list: D000305:Adrenal Cortex Hormones; D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C036309:fibrin fragment D; D014841:von Willebrand Factor; D011239:Prednisolone; D013917:Thrombin
keywords: corticosteroids; fibrinolysis; healthy volunteers; hemostasis; pulmonary embolism; therapy