Extracellular vesicle–associated procoagulant activity is highest the first 3 hours after trauma and thereafter declines substantially: A prospective observational pilot study

Rognes, Ingrid Nygren; Hellum, Marit; Ottestad, William; Bache, Kristi G; Eken, Torsten; Henriksson, Carola E.

doi:10.1097/ta.0000000000003333

Cited by 5 publications

(5 citation statements)

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“…These authors also demonstrated that ADP promotes calcium release from intracellular stores, which in turn is responsible for the regulation of proplatelet formation and subsequent enhancement of platelet function [11]. This ADPdependent platelet activation relies on the increase in cytosolic calcium concentrations [13,15]. Their studies confirmed that pharmacologic blockade of the increase in intracellular calcium prevented the natural platelet response to ADP, thus interfering with the release of platelet factors which augment platelet aggregation [11].…”

Section: Discussionmentioning

confidence: 86%

“…This increase in intracellular calcium is essential for platelet production and activation [14]. Mks develop cytoplasmic filaments called proplatelets; which, under the influence of various enzymes, produce platelets [15]. This process is stimulated by the release of Adenosine Diphosphate (ADP) from the dense bodies, further augmenting platelet formation [16].…”

Section: Discussionmentioning

confidence: 99%

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The Role of Calcium in Augmenting the Efficacy of Primary Homeostasis after Hemorrhagic Shock

JM,

AM,

2023

annhematoloncol

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Background: Traumatic Hemorrhagic Shock (THS) causes hypocalcemia (Ca). This study assesses how low Ca affects platelet (Plt) function. Study Design: A research registry was queried for 555 studies on 341 patients (pts) with THS requiring 14.2 units RBC, 8.4 units FFP, 3.6 units Plt, and 18.9 mEq Ca by end of O.R. (7.3 hours). Factors analyzed included Plt count, Ca, Bleeding Time (BT), Plt aggregation with ADP (PAadp) and collagen (PAcol), including Max PA, T1/2 PA, and rate PA, plus platelet release factors, beta thromboglobulin (BTG) and Plt PF-4. Studies were made in O.R. (26 pts) during fluid uptake phase II at 29 hours (216 pts), during fluid mobilization phase III at 56 hours (283 pts), and as outpatients (30 pts). Results: THS caused low Plts (1x10 SD) in O.R (107 ± 43), in phase II (96 ± 35), and in phase III (105 ± 59) and low Ca in O.R. (1.6 ± 0.3), in phase II (1.8 ± 0.2), and in phase III (2.1 ± 0.2). Low Plt and Ca correlated (p=<0.05) with PAadp and PAcol in O.R., phase II, and phase III. Ca correlated directly with Plt count, aggregation, BTG and PF-4, and inversely with BT. All outpatient studies were normal. Conclusion: THS causes Ca which leads to low Plt and impaired function. Routine Ca supplementation is recommended for THS.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

The Role of Calcium in Augmenting the Efficacy of Primary Homeostasis after Hemorrhagic Shock

JM,

AM,

2023

annhematoloncol

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“…This indicates a balance shift toward fibrinolysis during recovery which could be detrimental. EVs also have a transient hypercoagulable function and may play a role in the early phase of haemostasis after injury in trauma patients, with an increased concentration in the first 3 h after injury (Rognes et al., 2021 ). The altered temporal profiles of clotting cascade factors in ME/CFS EVs post‐exercise reveals a disruption in the haemostatic balance between clot formation and fibrinolysis.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases and sedentary controls in response to maximal exercise

Giloteaux,

Glass,

Germain

et al. 2024

J of Extracellular Vesicle

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In healthy individuals, physical exercise improves cardiovascular health and muscle strength, alleviates fatigue and reduces the risk of chronic diseases. Although exercise is suggested as a lifestyle intervention to manage various chronic illnesses, it negatively affects people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), who suffer from exercise intolerance. We hypothesized that altered extracellular vesicle (EV) signalling in ME/CFS patients after an exercise challenge may contribute to their prolonged and exacerbated negative response to exertion (post‐exertional malaise). EVs were isolated by size exclusion chromatography from the plasma of 18 female ME/CFS patients and 17 age‐ and BMI‐matched female sedentary controls at three time points: before, 15 min, and 24 h after a maximal cardiopulmonary exercise test. EVs were characterized using nanoparticle tracking analysis and their protein cargo was quantified using Tandem Mass Tag‐based (TMT) proteomics. The results show that exercise affects the EV proteome in ME/CFS patients differently than in healthy individuals and that changes in EV proteins after exercise are strongly correlated with symptom severity in ME/CFS. Differentially abundant proteins in ME/CFS patients versus controls were involved in many pathways and systems, including coagulation processes, muscle contraction (both smooth and skeletal muscle), cytoskeletal proteins, the immune system and brain signalling.

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“…Our study also did not demonstrate a difference in the levels of EVs between severely and minimally injured patients. Other investigators have shown that lower levels of phosphatidylserine-expressing EVs on admission were associated with higher transfusion rates and mortality (13)(14)(15)(16)27). This may be due to lower levels of procoagulant EVs and especially of platelet-derived extracellular vesicles (PEVs), being involved in a consumptive process such that PEVs cannot be accurately measured systemically.…”

Section: Discussionmentioning

confidence: 99%

Trauma-Derived Extracellular Vesicles Are Sufficient to Induce Endothelial Dysfunction and Coagulopathy

Zeineddin

Dong

et al. 2022

Shock

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Introduction: Although a number of studies have demonstrated increased release of extracellular vesicles (EVs) and changes in their origin differentials after trauma, the biologic significance of EVs is not well understood. We hypothesized that EVs released after trauma/hemorrhagic shock (HS) contribute to endotheliopathy and coagulopathy. To test this hypothesis, adoptive transfer experiments were performed to determine whether EVs derived from severely injured patients in shock were sufficient to induce endothelial dysfunction and coagulopathy. Methods: Total EVs were enriched from plasma of severely injured trauma/HS patients or minimally injured patients by ultracentrifugation and characterized for size and numbers. Under isoflurane anesthesia, noninjured naive C57BL/6J mice were administered EVs at varying concentrations and compared with mice receiving equal volume vehicle (phosphate-buffered saline (PBS)) or to mice receiving EVs from minimally injured patients. Thirty minutes after injection, mice were sacrificed, and blood was collected for thrombin generation (thrombin-antithrombin, thrombin-antithrombin complex [TAT] assay) and syndecan-1 by enzyme-linked immunoabsorbent assay (ELISA). Lungs were harvested for examination of histopathologic injury and costained with von Willebrand factor and fibrin to identify intravascular coagulation. Bronchial alveolar lavage fluid was aspirated from lungs for protein measurement as an indicator of the endothelial permeability. Data are presented as mean ± SD, P < 0.05 was considered significant, and t test was used. Results: An initial proof-of-concept experiment was performed in naive mice receiving EVs purified from severely injured trauma/HS patients (Injury Severity Score [ISS], 34 ± 7) at different concentrations (5 Â 10 6 to 3.1 Â 10 9 /100 μL/mouse) and compared with PBS (control) mice. Neither TAT nor syndecan-1 levels were significantly different between groups at 30 minutes after EV infusion. However, lung vascular permeability and histopathologic injury were significantly higher in the EV group, and lung tissues demonstrated intravascular fibrin deposition. Based on these data, EVs from severely injured trauma/HS patients (ISS, 32 ± 6) or EVs from minimally injured patients (ISS, 8 ± 3) were administered to naive mice at higher concentrations (1 Â 10 9 to 1 Â 10 10 EV/100 μL/mouse). Compared with mice receiving EVs from minimally injured patients, plasma TAT and syndecan-1 levels were significantly higher in the trauma/HS EV group. Similarly, bronchial alveolar lavage protein and lung histopathologic injury were higher in the trauma/HS EV group, and lung tissues demonstrated enhanced intravascular fibrin deposition. Conclusion: These data demonstrate that trauma/HS results in the systemic release of EVs, which are capable of inducing endotheliopathy as demonstrated by elevated syndecan-1 and increased permeability and coagulopathy as demonstrated by increased TAT and intravascular fibrin deposition. Targeting trauma-induced EVs may represent a novel ther...

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Extracellular vesicle–associated procoagulant activity is highest the first 3 hours after trauma and thereafter declines substantially: A prospective observational pilot study

Abstract: Supplemental digital content is available in the text.

Cited by 5 publications

References 53 publications

The Role of Calcium in Augmenting the Efficacy of Primary Homeostasis after Hemorrhagic Shock

The Role of Calcium in Augmenting the Efficacy of Primary Homeostasis after Hemorrhagic Shock

Dysregulation of extracellular vesicle protein cargo in female myalgic encephalomyelitis/chronic fatigue syndrome cases and sedentary controls in response to maximal exercise

Trauma-Derived Extracellular Vesicles Are Sufficient to Induce Endothelial Dysfunction and Coagulopathy

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