title: Circadian rhythms of hemostatic factors in tetraplegia: a double-blind, randomized, placebo-controlled cross-over study of melatonin.
abstract: METHODS
  This is a double-blind, randomized, placebo-controlled cross-over study of melatonin in complete tetraplegia.
  
  
  OBJECTIVE
  Tetraplegic patients have an increased risk of venous thrombosis despite prophylaxis, blunted variations in melatonin and altered circadian variation of several hemostatic markers. To examine whether melatonin could modify the regulation of hemostasis, we measured plasma melatonin and several markers of hemostasis in tetraplegic subjects with or without melatonin supplement.
  
  
  METHODS
  The study was conducted in the Section for Spinal Cord Injury, Sunnaas Hospital, Nesoddtangen, Norway.
  
  
  METHODS
  Six subjects with long-standing complete tetraplegia were included in this cross-over study with 2 mg of melatonin or placebo given 4 days before sampling. We also included six able-bodied men without any intervention. Plasma samples were then collected frequently during a 24-h awake/sleep cycle. The plasma concentrations of melatonin and the various markers were analyzed using linear mixed models.
  
  
  RESULTS
  The 24-h profiles of prothrombin fragment 1+2 and von Willebrand factor, but not D-dimer, activated FVII, tissue factor pathway inhibitor and plasminogen activator inhibitor type 1, differed (P<0.05) between tetraplegic patients and able-bodied subjects. The absolute plasma concentration of activated FVII was higher (P<0.05) among the able-bodied compared with the tetraplegic groups. Supplementation of melatonin had no impact on these findings.
  
  
  CONCLUSIONS
  We found differences in circadian variation of several hemostatic markers between able-bodied and tetraplegics. These differences were apparently unrelated to fluctuations in the melatonin concentrations, suggesting little or no role of melatonin in the regulation of hemostasis in tetraplegia.
  
  
  BACKGROUND
  Financial support was provided from the Throne Holst Foundation.
authors: Sunnaas Hospital, Nesoddtangen, Norway.
authors: E
authors: E
authors: Kostovski
authors: 1] Akershus University Hospital, Nordbyhagen, Norway [2] Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors: A E A
authors: AE
authors: Dahm
authors: 1] Institute of Clinical Medicine, University of Oslo, Oslo, Norway [2] Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
authors: M C
authors: MC
authors: Mowinckel
authors: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors: A
authors: A
authors: Stranda
authors: 1] Institute of Clinical Medicine, University of Oslo, Oslo, Norway [2] Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
authors: G
authors: G
authors: Skretting
authors: Institute of Medical Biology, Faculty of Health Sciences, The Arctic University of Norway, Tromsø, Norway.
authors: B
authors: B
authors: Østerud
authors: 1] Institute of Clinical Medicine, University of Oslo, Oslo, Norway [2] Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway [3] Department of Hematology, Oslo University Hospital, Oslo, Norway.
authors: P M
authors: PM
authors: Sandset
authors: 1] Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway [2] Department of Hematology, Oslo University Hospital, Oslo, Norway.
authors: P O
authors: PO
authors: Iversen
mesh_terms: D000328:Adult; D002491:Central Nervous System Agents / Q000097:blood / Q000627:therapeutic use*; D066193:Cervical Cord / Q000293:injuries; D002940:Circadian Rhythm / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008550:Melatonin / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D009664:Norway; D011782:Quadriplegia / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D013119:Spinal Cord Injuries / Q000097:blood / Q000150:complications / Q000188:drug therapy
chemical_list: D002491:Central Nervous System Agents; D008550:Melatonin
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