Platelets retain inducible alpha granule secretion by P‐selectin expression but exhibit mechanical dysfunction during trauma‐induced coagulopathy
Author(s): ,
Alexander E. St. John
Affiliations:
Department of Emergency Medicine, University of Washington, Seattle, USA. Bloodworks Northwest Research Institute, Seattle, USA
Correspondence: Dr. Alexander St. John, 325 9th Ave, Box 359702, Seattle, WA 98104, USA|Tel.: +1 206 744 4099|E‐mail: aestjohn@uw.edu
,
Jason C. Newton
Affiliations:
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, USA
,
Erika J. Martin
Affiliations:
Coagulation Advancement Laboratory, Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University, Richmond, USA
,
Bassem M. Mohammed
Affiliations:
Coagulation Advancement Laboratory, Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University, Richmond, USA. Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt
,
Daniel Contaifer
Affiliations:
Coagulation Advancement Laboratory, Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University, Richmond, USA
,
Jessica L. Saunders
Affiliations:
Coagulation Advancement Laboratory, Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University, Richmond, USA
,
Gretchen M. Brophy
Affiliations:
Coagulation Advancement Laboratory, Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University, Richmond, USA. Department of Neurosurgery, Virginia Commonwealth University, Richmond, USA
,
Bruce D. Spiess
Affiliations:
Department of Anesthesiology, University of Florida, Gainesville, USA
,
Kevin R. Ward
Affiliations:
Michigan Center for Integrative Research in Critical Care, University of Michigan, Ann Arbor, USA
,
Donald F. Brophy
Affiliations:
Coagulation Advancement Laboratory, Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University, Richmond, USA
,
José A. López
Affiliations:
Bloodworks Northwest Research Institute, Seattle, USA. Division of Hematology, University of Washington, Seattle, USA
Nathan J. White
Affiliations:
Department of Emergency Medicine, University of Washington, Seattle, USA. Bloodworks Northwest Research Institute, Seattle, USA
ISTH Academy. St. John A. May 1, 2019; 273603
Alexander St. John
Alexander St. John
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Journal Abstract
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Background
Trauma‐induced coagulopathy (TIC) is a common and deadly bleeding disorder. Platelet dysfunction is present during TIC, but its mechanisms remain unclear. Platelets are currently thought to become “exhausted,” a state in which they have released their granule contents and can no longer aggregate or contract.
Methods
This prospective observational cohort study tested the hypothesis that platelet exhaustion is present during TIC and characterized the early time course of platelet dysfunction. Blood was collected from 95 adult trauma patients at a Level I trauma center at time of Emergency Department arrival and several time points over 72 h. Platelet activation state and function were characterized using CD62P (P‐selectin) and PAC‐1 surface membrane staining, platelet function analyzer (PFA‐100), aggregometry, viscoelastic platelet mapping, and, to test for exhaustion, their ability to express CD62P after ex vivo adenosine diphosphate (ADP) agonism. Platelet function was compared between patients with and without TIC, defined by prothrombin time ≥18 s.
Results
Platelets in TIC showed no initial increase in their level of surface activation markers or impairment of their capacity to express CD62P in response to ADP stimulation. However, TIC platelets were impaired in nearly all functional assays, spanning adhesion, aggregation, and contraction. These effects largely remained after controlling for platelet count and fibrinogen concentration and resolved after 8 h.
Conclusion
The TIC platelets exhibit early impairment of adhesion, aggregation, and contraction with retained alpha granule secretion ability, suggesting a specific mechanism of cytoskeletal or integrin dysfunction that is not a result of more general platelet exhaustion.
Keyword(s)
blood platelet disorders, hemorrhagic disorders, platelet activation, platelet aggregation, trauma
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