Dataset Information

Importance of catecholamine signaling in the development of platelet exhaustion after traumatic injury.

ABSTRACT:

Background

Impaired ex vivo platelet aggregation is common in trauma patients. The mechanisms driving these impairments remain incompletely understood, but functional platelet exhaustion due to excessive in vivo activation is implicated. Given platelet adrenoreceptors and known catecholamine surges after injury, impaired ex vivo platelet aggregation in trauma patients may be linked to catecholamine-induced functional platelet exhaustion.

Objective

To determine the relationship of catecholamines with platelet-dependent hemostasis after injury and to model catecholamine-induced functional platelet exhaustion in healthy donor platelets.

Patients/methods

Whole blood was collected from 67 trauma patients as part of a prospective cohort study. Platelet aggregometry and rotational thromboelastometry were performed, and plasma epinephrine (EPI) and norepinephrine (NE) concentrations were measured. The effect of catecholamines on healthy donor platelets was examined in a microfluidic model, with platelet aggregometry, and by flow cytometry examining surface markers of platelet activation.

Results

In trauma patients, EPI and NE were associated with impaired platelet aggregation (both p < 0.05), and EPI was additionally associated with decreased viscoelastic clot strength, increased fibrinolysis, and mortality (all p < 0.05). In healthy donors, short duration incubation with EPI enhanced platelet aggregation, platelet adhesion under flow, and increased glycoprotein IIb/IIIa activation, while weaker effects were observed with NE. Compared with short incubation, longer incubation with EPI resulted in decreased platelet adhesion, platelet aggregation, and surface expression of glycoprotein IIb/IIIa.

Conclusions

These findings suggest sympathoadrenal activation in trauma patients contributes to impaired ex vivo platelet aggregation, which mechanistically may be explained by a functionally exhausted platelet phenotype under prolonged exposure to high plasma catecholamine levels.

SUBMITTER: Matthay ZA

PROVIDER: S-EPMC10450647 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Importance of catecholamine signaling in the development of platelet exhaustion after traumatic injury.

Matthay Zachary A ZA Fields Alexander T AT Nunez-Garcia Brenda B Park John J JJ Jones Chayse C Leligdowicz Aleksandra A Hendrickson Carolyn M CM Callcut Rachael A RA Matthay Michael A MA Kornblith Lucy Z LZ

Journal of thrombosis and haemostasis : JTH 20220530 9

<h4>Background</h4>Impaired ex vivo platelet aggregation is common in trauma patients. The mechanisms driving these impairments remain incompletely understood, but functional platelet exhaustion due to excessive in vivo activation is implicated. Given platelet adrenoreceptors and known catecholamine surges after injury, impaired ex vivo platelet aggregation in trauma patients may be linked to catecholamine-induced functional platelet exhaustion.<h4>Objective</h4>To determine the relationship of ...[more]

PMID: 35592998

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Dataset Information

Importance of catecholamine signaling in the development of platelet exhaustion after traumatic injury.

Background

Objective

Patients/methods

Results

Conclusions

Publications

Importance of catecholamine signaling in the development of platelet exhaustion after traumatic injury.

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