Circadian rhythms of hemostatic factors in tetraplegia: a double-blind, randomized, placebo-controlled cross-over study of melatonin

• Published in: Spinal cord Vol. 53; no. 4; pp. 285 - 290
• Main Authors: Kostovski, E, Dahm, A E A, Mowinckel, M C, Stranda, A, Skretting, G, Østerud, B, Sandset, P M, Iversen, P O
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-04-2015; Nature Publishing Group; Springer Nature
• Subjects: 631/443/1338/567; 692/699/75/567; Adult; Anatomy; Biomedical and Life Sciences; Biomedicine; Central Nervous System Agents - blood; Central Nervous System Agents - therapeutic use; Cervical Cord - injuries; Circadian Rhythm - physiology; Cross-Over Studies; Double-Blind Method; Human Physiology; Humans; Male; Melatonin - blood; Melatonin - therapeutic use; Middle Aged; Neurochemistry; Neuropsychology; Neurosciences; Norway; Original; original-article; Quadriplegia - blood; Quadriplegia - drug therapy; Quadriplegia - etiology; Spinal Cord Injuries - blood; Spinal Cord Injuries - complications; Spinal Cord Injuries - drug therapy; Norway
• ISSN: 1362-4393; 1476-5624; 1476-5624
• DOI: 10.1038/sc.2014.243

Study design:
This is a double-blind, randomized, placebo-controlled cross-over study of melatonin in complete tetraplegia.
Objectives:
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.
Setting:
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.
Sponsorship:
Financial support was provided from the Throne Holst Foundation.