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In vitro norepinephrine significantly activates isolated platelets from healthy volunteers and critically ill patients following severe traumatic brain injury.

Tschuor C, Asmis LM, Lenzlinger PM, Tanner M, Härter L, Keel M, Stocker R, Stover JF - Crit Care (2008)

Bottom Line: During the first week following TBI, norepinephrine-mediated stimulation of isolated platelets was significantly reduced compared with volunteers (control).In the second week, the number of P-selectin- and microparticle-positive platelets was significantly decreased by 60% compared with the first week and compared with volunteers.This, however, was associated with a significantly increased susceptibility to norepinephrine-mediated stimulation, exceeding changes observed in volunteers and TBI patients during the first week.

View Article: PubMed Central - HTML - PubMed

Affiliation: Surgical Intensive Care Medicine, University Hospital Zuerich, Raemistrasse 100, CH 8091 Zuerich, Switzerland.

ABSTRACT

Introduction: Norepinephrine, regularly used to increase systemic arterial blood pressure and thus improve cerebral perfusion following severe traumatic brain injury (TBI), may activate platelets. This, in turn, could promote microthrombosis formation and induce additional brain damage.

Methods: The objective of this study was to investigate the influence of norepinephrine on platelets isolated from healthy volunteers and TBI patients during the first two post-traumatic weeks. A total of 18 female and 18 male healthy volunteers of different age groups were recruited, while 11 critically ill TBI patients admitted consecutively to our intensive care unit were studied. Arterial and jugular venous platelets were isolated from norepinephrine-receiving TBI patients; peripheral venous platelets were studied in healthy volunteers. Concentration-dependent functional alterations of isolated platelets were analyzed by flow cytometry, assessing changes in surface P-selectin expression and platelet-derived microparticles before and after in vitro stimulation with norepinephrine ranging from 10 nM to 100 microM. The thrombin receptor-activating peptide (TRAP) served as a positive control.

Results: During the first week following TBI, norepinephrine-mediated stimulation of isolated platelets was significantly reduced compared with volunteers (control). In the second week, the number of P-selectin- and microparticle-positive platelets was significantly decreased by 60% compared with the first week and compared with volunteers. This, however, was associated with a significantly increased susceptibility to norepinephrine-mediated stimulation, exceeding changes observed in volunteers and TBI patients during the first week. This pronounced norepinephrine-induced responsiveness coincided with increased arterio-jugular venous difference in platelets, reflecting intracerebral adherence and signs of cerebral deterioration reflected by elevated intracranial pressure and reduced jugular venous oxygen saturation.

Conclusion: Clinically infused norepinephrine might influence platelets, possibly promoting microthrombosis formation. In vitro stimulation revealed a concentration- and time-dependent differential level of norepinephrine-mediated platelet activation, possibly reflecting changes in receptor expression and function. Whether norepinephrine should be avoided in the second post-traumatic week and whether norepinephrine-stimulated platelets might induce additional brain damage warrant further investigations.

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Changes in expression of surface P-selectin in platelets isolated from severe traumatic brain injury patients compared with healthy controls. The relative number of P-selectin-positive arterial and jugular venous platelets was significantly decreased during the second week. * P <0.05 versus controls and first week; analysis of variance on ranks.
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Figure 3: Changes in expression of surface P-selectin in platelets isolated from severe traumatic brain injury patients compared with healthy controls. The relative number of P-selectin-positive arterial and jugular venous platelets was significantly decreased during the second week. * P <0.05 versus controls and first week; analysis of variance on ranks.

Mentions: During the second post-traumatic week, the number of P-selectin-positive cells expressed as the relative amount of all gated platelets was significantly reduced compared with healthy controls and the first week (Figure 3). Similar changes were also observed for CD61-positive microparticles (data not shown). Incubation with TRAP, however, maximally increased the relative amount of P-selectin-positive (Figure 4) and microparticle-positive (data not shown) platelets, which was mostly sustained in platelets isolated during the second week (Figure 4). Overall, there was no significant difference between arterial and jugular venous platelets (Figures 3 and 4).


In vitro norepinephrine significantly activates isolated platelets from healthy volunteers and critically ill patients following severe traumatic brain injury.

Tschuor C, Asmis LM, Lenzlinger PM, Tanner M, Härter L, Keel M, Stocker R, Stover JF - Crit Care (2008)

Changes in expression of surface P-selectin in platelets isolated from severe traumatic brain injury patients compared with healthy controls. The relative number of P-selectin-positive arterial and jugular venous platelets was significantly decreased during the second week. * P <0.05 versus controls and first week; analysis of variance on ranks.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2481479&req=5

Figure 3: Changes in expression of surface P-selectin in platelets isolated from severe traumatic brain injury patients compared with healthy controls. The relative number of P-selectin-positive arterial and jugular venous platelets was significantly decreased during the second week. * P <0.05 versus controls and first week; analysis of variance on ranks.
Mentions: During the second post-traumatic week, the number of P-selectin-positive cells expressed as the relative amount of all gated platelets was significantly reduced compared with healthy controls and the first week (Figure 3). Similar changes were also observed for CD61-positive microparticles (data not shown). Incubation with TRAP, however, maximally increased the relative amount of P-selectin-positive (Figure 4) and microparticle-positive (data not shown) platelets, which was mostly sustained in platelets isolated during the second week (Figure 4). Overall, there was no significant difference between arterial and jugular venous platelets (Figures 3 and 4).

Bottom Line: During the first week following TBI, norepinephrine-mediated stimulation of isolated platelets was significantly reduced compared with volunteers (control).In the second week, the number of P-selectin- and microparticle-positive platelets was significantly decreased by 60% compared with the first week and compared with volunteers.This, however, was associated with a significantly increased susceptibility to norepinephrine-mediated stimulation, exceeding changes observed in volunteers and TBI patients during the first week.

View Article: PubMed Central - HTML - PubMed

Affiliation: Surgical Intensive Care Medicine, University Hospital Zuerich, Raemistrasse 100, CH 8091 Zuerich, Switzerland.

ABSTRACT

Introduction: Norepinephrine, regularly used to increase systemic arterial blood pressure and thus improve cerebral perfusion following severe traumatic brain injury (TBI), may activate platelets. This, in turn, could promote microthrombosis formation and induce additional brain damage.

Methods: The objective of this study was to investigate the influence of norepinephrine on platelets isolated from healthy volunteers and TBI patients during the first two post-traumatic weeks. A total of 18 female and 18 male healthy volunteers of different age groups were recruited, while 11 critically ill TBI patients admitted consecutively to our intensive care unit were studied. Arterial and jugular venous platelets were isolated from norepinephrine-receiving TBI patients; peripheral venous platelets were studied in healthy volunteers. Concentration-dependent functional alterations of isolated platelets were analyzed by flow cytometry, assessing changes in surface P-selectin expression and platelet-derived microparticles before and after in vitro stimulation with norepinephrine ranging from 10 nM to 100 microM. The thrombin receptor-activating peptide (TRAP) served as a positive control.

Results: During the first week following TBI, norepinephrine-mediated stimulation of isolated platelets was significantly reduced compared with volunteers (control). In the second week, the number of P-selectin- and microparticle-positive platelets was significantly decreased by 60% compared with the first week and compared with volunteers. This, however, was associated with a significantly increased susceptibility to norepinephrine-mediated stimulation, exceeding changes observed in volunteers and TBI patients during the first week. This pronounced norepinephrine-induced responsiveness coincided with increased arterio-jugular venous difference in platelets, reflecting intracerebral adherence and signs of cerebral deterioration reflected by elevated intracranial pressure and reduced jugular venous oxygen saturation.

Conclusion: Clinically infused norepinephrine might influence platelets, possibly promoting microthrombosis formation. In vitro stimulation revealed a concentration- and time-dependent differential level of norepinephrine-mediated platelet activation, possibly reflecting changes in receptor expression and function. Whether norepinephrine should be avoided in the second post-traumatic week and whether norepinephrine-stimulated platelets might induce additional brain damage warrant further investigations.

Show MeSH
Related in: MedlinePlus