Reduced peak, but no diurnal variation, in thrombin generation upon melatonin supplementation in tetraplegia

Per Ole Iversen; Anders Dahm; Grethe Skretting; Marie-Christine Mowinckel; Annicke Stranda; Bjarne Østerud; Per Morten Sandset; Emil Kostovski

doi:10.1160/TH15-05-0396

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 114(05): 964-968
DOI: 10.1160/TH15-05-0396

Coagulation and Fibrinolysis

Schattauer GmbH

Reduced peak, but no diurnal variation, in thrombin generation upon melatonin supplementation in tetraplegia

A randomised, placebo-controlled study

Per Ole Iversen

¹Department of Nutrition, IMB, University of Oslo, Oslo, Norway

²Department of Haematology, Oslo University Hospital, Oslo, Norway

,

Anders Dahm

³Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway

⁴Department of Haematology, Akershus University Hospital, Oslo, Norway

⁵Institute of Clinical Medicine, University of Oslo, Oslo, Norway

,

Grethe Skretting

²Department of Haematology, Oslo University Hospital, Oslo, Norway

³Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway

,

Marie-Christine Mowinckel

²Department of Haematology, Oslo University Hospital, Oslo, Norway

,

Annicke Stranda

¹Department of Nutrition, IMB, University of Oslo, Oslo, Norway

,

Bjarne Østerud

⁶Jebsen TREC, IMB, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway

,

Per Morten Sandset

²Department of Haematology, Oslo University Hospital, Oslo, Norway

³Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway

⁵Institute of Clinical Medicine, University of Oslo, Oslo, Norway

,

Emil Kostovski

⁵Institute of Clinical Medicine, University of Oslo, Oslo, Norway

⁷Sunnaas Rehabilitation Hospital, Nesoddtangen, Norway

› Author Affiliations

Abstract

Summary

Tetraplegic patients have increased risk of venous thrombosis despite anti-thrombotic prophylaxis. Moreover, they have blunted plasma variations in melatonin and altered diurnal variation of several haemostatic markers, compared with able-bodied. However, whether healthy individuals and tetraplegic patients, with or without melatonin, display abnormalities in thrombin generation during a 24-hour (h) cycle, is unknown. We therefore used the Calibrated Automated Thrombogram (CAT) assay to examine diurnal variations and the possible role of melatonin in thrombin generation. Six men with long-standing complete tetraplegia were included in a randomised placebo-controlled cross-over study with melatonin supplementation (2 mg, 4 consecutive nights), whereas six healthy, able-bodied men served as controls. Ten plasma samples were collected frequently during a 24-h awake/sleep cycle. No significant diurnal variation of any of the measured CAT indices was detected in the three study groups. Whereas endogenous thrombin potential (ETP) was independent (p > 0.05) of whether the tetraplegic men received melatonin or placebo, melatonin decreased (p = 0.005) peak values in tetraplegia compared with those given placebo. Able-bodied men had lower (p = 0.019) ETP and Lag-Time (p = 0.018) compared with tetraplegics receiving placebo. Neither the Time-to-Peak nor the Start-Tail was affected (p > 0.05) by melatonin in tetraplegia. In conclusion, indices of thrombin generation are not subjected to diurnal variation in healthy able-bodied or tetraplegia, but peak thrombin generation is reduced in tetraplegic men receiving oral melatonin.

Keywords

Diurnal rhythm - haemostasis - melatonin - nervous system - thrombin

Full Text

References

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