Hemostatic responses to exercise, dehydration, and simulated bleeding in heat-stressed humans

Matthew A. Borgman, Morten Zaar, James K. Aden, Zachary J. Schlader, Daniel Gagnon, Eric Rivas, Jena Kern, Natalie J. Koons, Victor A. Convertino, Andrew P. Cap, Craig G Crandall

Research output: Contribution to journalArticle

Abstract

Heat stress followed by an accompanying hemorrhagic challenge may influence hemostasis. We tested the hypothesis that hemostatic responses would be increased by passive heat stress, as well as exercise-induced heat stress, each with accompanying central hypovolemia to simulate a hemorrhagic insult. In aim 1, subjects were exposed to passive heating or normothermic time control, each followed by progressive lower-body negative pressure (LBNP) to presyncope. In aim 2 subjects exercised in hyperthermic environmental conditions, with and without accompanying dehydration, each also followed by progressive LBNP to presyncope. At baseline, pre-LBNP, and post-LBNP (<1, 30, and 60 min), hemostatic activity of venous blood was evaluated by plasma markers of hemostasis and thrombelastography. For aim 1, both hyperthermic and normothermic LBNP (H-LBNP and N-LBNP, respectively) resulted in higher levels of factor V, factor VIII, and von Willebrand factor antigen compared with the time control trial (all P < 0.05), but these responses were temperature independent. Hyperthermia increased fibrinolysis [clot lysis 30 min after the maximal amplitude reflecting clot strength (LY30)] to 5.1% post-LBNP compared with 1.5% (time control) and 2.7% in N-LBNP ( P = 0.05 for main effect). Hyperthermia also potentiated increased platelet counts post-LBNP as follows: 274 K/µl for H-LBNP, 246 K/µl for N-LBNP, and 196 K/µl for time control ( P < 0.05 for the interaction). For aim 2, hydration status associated with exercise in the heat did not affect the hemostatic activity, but fibrinolysis (LY30) was increased to 6-10% when subjects were dehydrated compared with an increase to 2-4% when hydrated ( P = 0.05 for treatment). Central hypovolemia via LBNP is a primary driver of hemostasis compared with hyperthermia and dehydration effects. However, hyperthermia does induce significant thrombocytosis and by itself causes an increase in clot lysis. Dehydration associated with exercise-induced heat stress increases clot lysis but does not affect exercise-activated or subsequent hypovolemia-activated hemostasis in hyperthermic humans. Clinical implications of these findings are that quickly restoring a hemorrhaging hypovolemic trauma patient with cold noncoagulant fluids (crystalloids) can have serious deleterious effects on the body's innate ability to form essential clots, and several factors can increase clot lysis, which should therefore be closely monitored.

Original languageEnglish (US)
Pages (from-to)R145-R156
JournalAmerican journal of physiology. Regulatory, integrative and comparative physiology
Volume316
Issue number2
DOIs
StatePublished - Feb 1 2019

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Lower Body Negative Pressure
Hemostatics
Dehydration
Hot Temperature
Hemorrhage
Hypovolemia
Hemostasis
Fever
Syncope
Fibrinolysis
Exercise
Thrombelastography
Thrombocytosis
Factor V
Platelet Count
Heating

Keywords

  • coagulation
  • fibrinolysis
  • hyperthermia
  • hypovolemia
  • lower body negative pressure

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Hemostatic responses to exercise, dehydration, and simulated bleeding in heat-stressed humans. / Borgman, Matthew A.; Zaar, Morten; Aden, James K.; Schlader, Zachary J.; Gagnon, Daniel; Rivas, Eric; Kern, Jena; Koons, Natalie J.; Convertino, Victor A.; Cap, Andrew P.; Crandall, Craig G.

In: American journal of physiology. Regulatory, integrative and comparative physiology, Vol. 316, No. 2, 01.02.2019, p. R145-R156.

Research output: Contribution to journalArticle

Borgman, MA, Zaar, M, Aden, JK, Schlader, ZJ, Gagnon, D, Rivas, E, Kern, J, Koons, NJ, Convertino, VA, Cap, AP & Crandall, CG 2019, 'Hemostatic responses to exercise, dehydration, and simulated bleeding in heat-stressed humans', American journal of physiology. Regulatory, integrative and comparative physiology, vol. 316, no. 2, pp. R145-R156. https://doi.org/10.1152/ajpregu.00223.2018
Borgman, Matthew A. ; Zaar, Morten ; Aden, James K. ; Schlader, Zachary J. ; Gagnon, Daniel ; Rivas, Eric ; Kern, Jena ; Koons, Natalie J. ; Convertino, Victor A. ; Cap, Andrew P. ; Crandall, Craig G. / Hemostatic responses to exercise, dehydration, and simulated bleeding in heat-stressed humans. In: American journal of physiology. Regulatory, integrative and comparative physiology. 2019 ; Vol. 316, No. 2. pp. R145-R156.
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