Platelet dynamics during natural and pharmacologically induced torpor and forced hypothermia

Edwin L de Vrij; Pieter C Vogelaar; Maaike Goris; Martin C Houwertjes; Annika Herwig; George J Dugbartey; Ate S Boerema; Arjen M Strijkstra; Hjalmar R Bouma; Robert H Henning

doi:10.1371/journal.pone.0093218

Platelet dynamics during natural and pharmacologically induced torpor and forced hypothermia

PLoS One. 2014 Apr 10;9(4):e93218. doi: 10.1371/journal.pone.0093218. eCollection 2014.

Affiliations

¹ Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
² Sulfateq BV, Groningen, the Netherlands.
³ Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁴ Zoological Institute, University of Hamburg, Hamburg, Germany.
⁵ Department of Chronobiology, University of Groningen, Center for Behaviour & Neurosciences, Groningen, The Netherlands; Department of Molecular Neurobiology, University of Groningen, Center for Behavior & Neurosciences, Groningen, The Netherlands; Department of Nuclear Medicine & Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁶ Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Chronobiology, University of Groningen, Center for Behaviour & Neurosciences, Groningen, The Netherlands.
⁷ Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Abstract

Hibernation is an energy-conserving behavior in winter characterized by two phases: torpor and arousal. During torpor, markedly reduced metabolic activity results in inactivity and decreased body temperature. Arousal periods intersperse the torpor bouts and feature increased metabolism and euthermic body temperature. Alterations in physiological parameters, such as suppression of hemostasis, are thought to allow hibernators to survive periods of torpor and arousal without organ injury. While the state of torpor is potentially procoagulant, due to low blood flow, increased viscosity, immobility, hypoxia, and low body temperature, organ injury due to thromboembolism is absent. To investigate platelet dynamics during hibernation, we measured platelet count and function during and after natural torpor, pharmacologically induced torpor and forced hypothermia. Splenectomies were performed to unravel potential storage sites of platelets during torpor. Here we show that decreasing body temperature drives thrombocytopenia during torpor in hamster with maintained functionality of circulating platelets. Interestingly, hamster platelets during torpor do not express P-selectin, but expression is induced by treatment with ADP. Platelet count rapidly restores during arousal and rewarming. Platelet dynamics in hibernation are not affected by splenectomy before or during torpor. Reversible thrombocytopenia was also induced by forced hypothermia in both hibernating (hamster) and non-hibernating (rat and mouse) species without changing platelet function. Pharmacological torpor induced by injection of 5'-AMP in mice did not induce thrombocytopenia, possibly because 5'-AMP inhibits platelet function. The rapidness of changes in the numbers of circulating platelets, as well as marginal changes in immature platelet fractions upon arousal, strongly suggest that storage-and-release underlies the reversible thrombocytopenia during natural torpor. Possibly, margination of platelets, dependent on intrinsic platelet functionality, governs clearance of circulating platelets during torpor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Diphosphate / chemistry
Animals
Arousal / physiology
Blood Platelets / cytology*
Body Temperature
Cricetinae
Female
Hibernation
Hypothermia, Induced*
Male
Mesocricetus
Mice
Mice, Inbred C57BL
P-Selectin / metabolism
Rats
Rats, Wistar
Seasons
Thrombocytopenia / physiopathology
Time Factors
Torpor*

Substances

P-Selectin
Adenosine Diphosphate

Grants and funding

An MD/PhD grant was provided by the University Medical Center Groningen on behalf of Hjalmar Bouma. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.