Coagulation abnormalities contribute to poor outcomes in critically ill patients. In trauma patients exposed to a hot environment, a systemic inflammatory response syndrome, elevated body temperature, and reduced central blood volume occur in parallel with changes in hemostasis and endothelial damage. The objective of this study was to evaluate whether experimentally elevated body temperature and reduced central blood volume (CBV) per se affects hemostasis and endothelial activation.
Eleven healthy volunteers were subjected to heat stress, sufficient to elevate core temperature, and progressive reductions in CBV by lower body negative pressure (LBNP). Changes in hemostasis were evaluated by whole blood haemostatic assays, standard hematologic tests and by plasma biomarkers of coagulation and endothelial activation/disruption.
Elevated body temperature and decreased CBV resulted in coagulation activation evidenced by shortened activated partial tromboplastin time (−9% [IQR −7; −4]), thrombelastography: reduced reaction time (−15% [−24; −4]) and increased maximum amplitude (+4% (2; 6)), all P < 0.05. Increased fibrinolysis was documented by elevation of D-dimer (+53% (12; 59), P = 0.016). Plasma adrenaline and noradrenaline increased 198% (83; 346) and 234% (174; 363) respectively (P = 0.006 and P = 0.003).
This experiment revealed emerging hypercoagulability in response to elevated body temperature and decreased CBV, whereas no effect on the endothelium was observed. We hypothesize that elevated body temperature and reduced CBV contributes to hypercoagulability, possibly due to moderate sympathetic activation, in critically ill patients and speculate that normalization of body temperature and CBV may attenuate this hypercoagulable response.
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- Inflammation and coagulation.Crit Care Med. 2010; 38: S26
- Fever in the critically ill: a review of epidemiology, immunology, and management.J Intensive Care Med. 2012; 27: 290
Buller MJ, Wallis DC, Karis AJ, et al. Thermal-work Strain during Marine Rifle Squad Operations in Iraq (Summer 2008). U.S. Army Research Institute of Environmental Medicine; 2008.
- Admission hypo- or hyperthermia and survival after trauma in civilian and military environments.Int J Emerg Med. 2011; 4: 35
- Volume responsiveness.Curr Opin Crit Care. 2007; 13: 549
- Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine.Chest. 1992; 101: 1644
- Hemostatic disturbances in patients with systemic inflammatory response syndrome (SIRS) and associated acute renal failure (ARF).Thromb Res. 2000; 100: 19
- The endothelial glycocalyx: composition, functions, and visualization.Pflugers Arch. 2007; 454: 345
- Effects of passive heating on central blood volume and ventricular dimensions in humans.J Physiol. 2008; 586: 293
- Hemodynamic effects of graded hypovolemia and vasodepressor syncope induced by lower body negative pressure.Am Heart J. 1968; 76: 799
- Activation of coagulation during therapeutic whole body hyperthermia.Thromb Res. 1986; 43: 353
- Early activation of the coagulation system during lower body negative pressure.Clin Physiol Funct Imaging. 2009; 29: 427
- Heat stress, plasma concentrations of adrenaline, noradrenaline, 5-hydroxytryptamine and cortisol, mood state and cognitive performance.Int J Psychophysiol. 2006; 61: 204
- Cardiovascular and autonomic responses to lower body negative pressure: do not explain gender differences in orthostatic tolerance.Clin Auton Res. 2003; 13: 36
- Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo.Eur J Haematol. 2000; 65: 357
- Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation.Med Hypotheses. 2010; 75: 564
- Effect of heat stress on cardiac output and systemic vascular conductance during simulated hemorrhage to presyncope in young men.Am J Physiol Heart Circ Physiol. 2012; 302: H1756
- Lower body negative pressure as a model to study progression to acute hemorrhagic shock in humans.J Appl Physiol. 2004; 96: 1249
- Thrombelastography and tromboelastometry in assessing coagulopathy in trauma.Scand J Trauma Resusc Emerg Med. 2009; 17: 45
- The electronic aggregometer: a novel device for assessing platelet behavior in blood.J Pharmacol Methods. 1980; 3: 135
- Detection of tPA-induced hyperfibrinolysis in whole blood by RapidTEG, KaolinTEG, and functional fibrinogenTEG in healthy individuals.Clin Appl Thromb Hemost. 2012; 18: 638
- Effect of circulating epinephrine on platelet function and hematocrit.Hypertension. 1995; 25: 1096
- Effects of changes in temperature (local and central) on plasma fibrinolytic activity.J Clin Pathol. 1973; 26: 248
- Blood coagulation activation and fibrinolysis during a downhill marathon run.Blood Coagul Fibrinolysis. 2007; 18: 435
- Thromboelastography maximum amplitude predicts postoperative thrombotic complications including myocardial infarction.Anesth Analg. 2005; 100: 1576
- Four-day antithrombin therapy does not seem to attenuate hypercoagulability in patients suffering from sepsis.Crit Care. 2006; 10: R160
- Diagnosis of hypersplenism with the epinephrine stimulation test—23 years of experience at a tertiary care hospital.Swiss Med Weekly. 2012; 141: w13324
- The hypersplenic spleen. A contractile reservoir of granulocytes and platelets.Arch Intern Med. 1985; 145: 651
- Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system.N Engl J Med. 1980; 303: 436
- Endogenous and exogenous catecholamines in critical care medicine.Crit Care Med. 1982; 10: 409
- Catecholamine-mediated injury to endothelium in rabbit perfused aorta: a quantitative analysis by scanning electron microscopy.Cor Vasa. 1985; 27: 456
- A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients.Ann Surg. 2011; 254: 194
- Acute myocardial infarction is associated with endothelial glycocalyx and cell damage and a parallel increase in circulating catecholamines.Crit Care. 2013; 17: R32
- Human endotoxemia as a model of systemic inflammation.Curr Med Chem. 2008; 15: 1697
- Discrepant fibrinolytic response in plasma and whole blood during experimental endotoxemia in healthy volunteers.PLoS One. 2013; 8: e59368
- Sympathetic overstimulation during critical illness: adverse effects of adrenergic stress.J Intensive Care Med. 2009; 24: 293
- Effect of volume loading on the Frank–Starling relation during reductions in central blood volume in heat-stressed humans.J Physiol. 2010; 588: 3333
- Fever control using external cooling in septic shock: a randomized controlled trial.Am J Respir Crit Care Med. 2012; 185: 1088
- Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis.J Trauma. 2008; 64: 1211
- Pathophysiology of early trauma-induced coagulopathy: emerging evidence for hemodilution and coagulation factor depletion.J Trauma. 2011; 70: 1401
Published online: July 01, 2013
Accepted: June 6, 2013
Received in revised form: May 20, 2013
Received: December 20, 2012
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.