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Article ; Online: Platelets in Hemostasis, Thrombosis, and Inflammation After Major Trauma.

Vulliamy, Paul / Armstrong, Paul C

Arteriosclerosis, thrombosis, and vascular biology

2024 Volume 44, Issue 3, Page(s) 545–557

Abstract: Trauma currently accounts for 10% of the total global burden of disease and over 5 million deaths per year, making it a leading cause of morbidity and mortality worldwide. Although recent advances in early resuscitation have improved early survival from ... ...

Abstract	Trauma currently accounts for 10% of the total global burden of disease and over 5 million deaths per year, making it a leading cause of morbidity and mortality worldwide. Although recent advances in early resuscitation have improved early survival from critical injury, the mortality rate in patients with major hemorrhage approaches 50% even in mature trauma systems. A major determinant of clinical outcomes from a major injury is a complex, dynamic hemostatic landscape. Critically injured patients frequently present to the emergency department with an acute traumatic coagulopathy that increases mortality from bleeding, yet, within 48 to 72 hours after injury will switch from a hypocoagulable to a hypercoagulable state with increased risk of venous thromboembolism and multiple organ dysfunction. This review will focus on the role of platelets in these processes. As effectors of hemostasis and thrombosis, they are central to each phase of recovery from injury, and our understanding of postinjury platelet biology has dramatically advanced over the past decade. This review describes our current knowledge of the changes in platelet behavior that occur following major trauma, the mechanisms by which these changes develop, and the implications for clinical outcomes. Importantly, supported by research in other disease settings, this review also reflects the emerging role of thromboinflammation in trauma including cross talk between platelets, innate immune cells, and coagulation. We also address the unresolved questions and significant knowledge gaps that remain, and finally highlight areas that with the further study will help deliver further improvements in trauma care.
MeSH term(s)	Humans ; Inflammation/complications ; Thrombosis/complications ; Hemostasis ; Blood Coagulation Disorders ; Hemorrhage/etiology ; Blood Platelets
Language	English
Publishing date	2024-01-18
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.123.318801
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Article ; Online: ASGBI trauma committee position statement: a national audit of trauma laparotomy in the UK - an unmet need.

Shepherd, Joanna M / Vulliamy, Paul / Marsden, Max E R / Hancorn, Kate

British journal of anaesthesia

2024 Volume 132, Issue 5, Page(s) 849–850

Abstract: Patients who undergo laparotomy for major trauma are amongst the most critically unwell patients, and they have high morbidity and mortality rates. Despite 20 yr of improvements in resuscitation practices, those who present with hypotension continue to ... ...

Abstract	Patients who undergo laparotomy for major trauma are amongst the most critically unwell patients, and they have high morbidity and mortality rates. Despite 20 yr of improvements in resuscitation practices, those who present with hypotension continue to have mortality rates of up to 50%. Currently there is no mechanism for capturing national audit data on these patients, leading to their exclusion from potential quality improvement initiatives. We argue that there is an unmet need for quality assurance in this patient cohort and outline possible mechanisms to address this.
MeSH term(s)	Humans ; Laparotomy ; Medical Audit ; Quality Improvement ; Hypotension ; United Kingdom ; Retrospective Studies
Language	English
Publishing date	2024-03-26
Publishing country	England
Document type	Editorial
ZDB-ID	80074-0
ISSN	1471-6771 ; 0007-0912
ISSN (online)	1471-6771
ISSN	0007-0912
DOI	10.1016/j.bja.2024.03.001
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Article ; Online: Does pre-injury clopidogrel use increase the risk of intracranial haemorrhage post head injury in adult patients? A systematic review and meta-analysis.

Moffatt, Samuel / Venturini, Sara / Vulliamy, Paul

Emergency medicine journal : EMJ

2022 Volume 40, Issue 3, Page(s) 175–181

Abstract: Background: Several current guidelines do not include antiplatelet use as an explicit indication for CT scan of the head following head injury. The impact of individual antiplatelet agent use on rates of intracranial haemorrhage is unclear. The primary ... ...

Abstract	Background: Several current guidelines do not include antiplatelet use as an explicit indication for CT scan of the head following head injury. The impact of individual antiplatelet agent use on rates of intracranial haemorrhage is unclear. The primary objective of this systematic review was to assess if clopidogrel monotherapy was associated with traumatic intracranial haemorrhage (tICH) on CT of the head within 24 hours of presentation following head trauma compared with no antithrombotic controls. Methods: Eligible studies were non-randomised studies with participants aged ≥18 years old with head injury. Studies had to have conducted CT of the head within 24 hours of presentation and contain a no antithrombotic control group and a clopidogrel monotherapy group.Eight databases were searched from inception to December 2020. Assessment of identified studies against inclusion criteria and data extraction were carried out independently and in duplicate by two authors.Quality assessment and risk of bias (ROB) were assessed using the Newcastle-Ottawa Quality Assessment tool and Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Meta-analysis was conducted using a random-effects model and reported as an OR and 95% CI. Results: Seven studies were eligible for inclusion with a total of 21 898 participants that were incorporated into the meta-analysis. Five studies were retrospective. Clopidogrel monotherapy was not significantly associated with an increase in risk of tICH compared with no antithrombotic controls (OR 0.97, 95% CI 0.54 to 1.75). Heterogeneity was high with an I Conclusion: Included studies were vulnerable to confounding and several were small-scale studies. The results should be interpreted with caution given the ROB identified. This study does not provide statistically significant evidence that clopidogrel monotherapy patients are at increased risk of tICH after head injury compared with no antithrombotic controls. Prospero registration number: CRD42020223541.
MeSH term(s)	Humans ; Adult ; Adolescent ; Clopidogrel ; Retrospective Studies ; Platelet Aggregation Inhibitors ; Craniocerebral Trauma/complications ; Intracranial Hemorrhage, Traumatic/chemically induced ; Intracranial Hemorrhage, Traumatic/complications
Chemical Substances	Clopidogrel (A74586SNO7) ; Platelet Aggregation Inhibitors
Language	English
Publishing date	2022-09-30
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	2040124-3
ISSN	1472-0213 ; 1472-0205
ISSN (online)	1472-0213
ISSN	1472-0205
DOI	10.1136/emermed-2021-212225
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Article ; Online: Sensitivity Analysis Does Not Alter Conclusions.

Foley, Megan Power / Walsh, Stewart R / Doolan, Nathalie / Vulliamy, Paul / McMonagle, Morgan / Aylwin, Christopher

European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery

2023 Volume 67, Issue 3, Page(s) 520–522

Language	English
Publishing date	2023-12-15
Publishing country	England
Document type	Letter
ZDB-ID	1225869-6
ISSN	1532-2165 ; 1078-5884
ISSN (online)	1532-2165
ISSN	1078-5884
DOI	10.1016/j.ejvs.2023.12.007
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Article ; Online: Bouveret syndrome: a rare cause of gastric outlet obstruction.

Smith, Christopher / Singh, Shailendra / Vulliamy, Paul / Mukherjee, Samrat

BMJ case reports

2021 Volume 14, Issue 4

Abstract: Bouveret syndrome is a rare cause of gastric outlet obstruction. It is characterised by the presence of an obstructing gallstone in the pylorus or proximal duodenum, which has travelled to its obstructing position via an acquired fistula. Our case ... ...

Abstract	Bouveret syndrome is a rare cause of gastric outlet obstruction. It is characterised by the presence of an obstructing gallstone in the pylorus or proximal duodenum, which has travelled to its obstructing position via an acquired fistula. Our case involves a 73-year-old man presenting to the acute surgical take with a 2-day history of right-sided abdominal pain and vomiting. His medical history included perforated cholecystitis treated with antibiotics and percutaneous gall bladder drainage, 1 year earlier. Examination and blood tests were suggestive of gastric outlet obstruction. CT abdomen and pelvis demonstrated a large gallstone obstructing the duodenum, confirming a diagnosis of Bouveret syndrome. The patient improved following gastrolithotomy, and was discharged 2 weeks postoperatively. Fistula formation is a complication of chronic cholecystitis and therefore Bouveret syndrome should be considered in patients with a background of gallstone disease presenting with gastric outlet obstruction.
MeSH term(s)	Aged ; Duodenum ; Gallstones/complications ; Gallstones/diagnostic imaging ; Gallstones/surgery ; Gastric Outlet Obstruction/etiology ; Gastric Outlet Obstruction/surgery ; Humans ; Male ; Pylorus ; Syndrome
Language	English
Publishing date	2021-04-22
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2020-240236
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Article ; Online: A new global fibrinolysis capacity assay for the sensitive detection of hyperfibrinolysis and hypofibrinogenemia in trauma patients.

Rossetto, Andrea / Torres, Tracy / Platton, Sean / Vulliamy, Paul / Curry, Nicola / Davenport, Ross

Journal of thrombosis and haemostasis : JTH

2023 Volume 21, Issue 10, Page(s) 2759–2770

Abstract: Background: Conventional clotting tests are not expeditious enough to allow timely targeted interventions in trauma, and current point-of-care analyzers, such as rotational thromboelastometry (ROTEM), have limited sensitivity for hyperfibrinolysis and ... ...

Abstract	Background: Conventional clotting tests are not expeditious enough to allow timely targeted interventions in trauma, and current point-of-care analyzers, such as rotational thromboelastometry (ROTEM), have limited sensitivity for hyperfibrinolysis and hypofibrinogenemia. Objectives: To evaluate the performance of a recently developed global fibrinolysis capacity (GFC) assay in identifying fibrinolysis and hypofibrinogenemia in trauma patients. Methods: Exploratory analysis of a prospective cohort of adult trauma patients admitted to a single UK major trauma center and of commercially available healthy donor samples was performed. Lysis time (LT) was measured in plasma according to the GFC manufacturer's protocol, and a novel fibrinogen-related parameter (percentage reduction in GFC optical density from baseline at 1 minute) was derived from the GFC curve. Hyperfibrinolysis was defined as a tissue factor-activated ROTEM maximum lysis of >15% or LT of ≤30 minutes. Results: Compared to healthy donors (n = 19), non-tranexamic acid-treated trauma patients (n = 82) showed shortened LT, indicative of hyperfibrinolysis (29 minutes [16-35] vs 43 minutes [40-47]; p < .001). Of the 63 patients without overt ROTEM-hyperfibrinolysis, 31 (49%) had LT of ≤30 minutes, with 26% (8 of 31) of them requiring major transfusions. LT showed increased accuracy compared to maximum lysis in predicting 28-day mortality (area under the receiver operating characteristic curve, 0.96 [0.92-1.00] vs 0.65 [0.49-0.81]; p = .001). Percentage reduction in GFC optical density from baseline at 1 minute showed comparable specificity (76% vs 79%) to ROTEM clot amplitude at 5 minutes from tissue factor-activated ROTEM with cytochalasin D in detecting hypofibrinogenemia but correctly reclassified >50% of the patients with false negative results, leading to higher sensitivity (90% vs 77%). Conclusion: Severe trauma patients are characterized by a hyperfibrinolytic profile upon admission to the emergency department. The GFC assay is more sensitive than ROTEM in capturing hyperfibrinolysis and hypofibrinogenemia but requires further development and automation.
MeSH term(s)	Adult ; Humans ; Fibrinolysis ; Afibrinogenemia/diagnosis ; Thromboplastin ; Prospective Studies ; Blood Coagulation Disorders ; Thrombelastography/methods ; Wounds and Injuries/complications ; Wounds and Injuries/diagnosis
Chemical Substances	Thromboplastin (9035-58-9)
Language	English
Publishing date	2023-05-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2023.05.005
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Zs.A 5805: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Editor's Choice - Systematic Review and Meta-Analysis of Lower Extremity Vascular Complications after Arterial Access for Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA): An Inevitable Concern?

Foley, Megan Power / Walsh, Stewart R / Doolan, Nathalie / Vulliamy, Paul / McMonagle, Morgan / Aylwin, Christopher

European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery

2023 Volume 66, Issue 1, Page(s) 103–118

Abstract: Objective: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to temporise non-compressible torso haemorrhage. Recent data have suggested that vascular access complications secondary to REBOA placement are higher than initially ... ...

Abstract	Objective: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to temporise non-compressible torso haemorrhage. Recent data have suggested that vascular access complications secondary to REBOA placement are higher than initially anticipated. This updated systematic review and meta-analysis aimed to determine the pooled incidence rate of lower extremity arterial complications after REBOA. Data sources: PubMed, Scopus, Embase, conference abstract listings, and clinical trial registries. Review methods: Studies including more than five adults undergoing emergency REBOA for exsanguinating haemorrhage that reported access site complications were eligible for inclusion. A pooled meta-analysis of vascular complications was performed using the DerSimonian-Laird weights for the random effects model, presented as a Forest plot. Further meta-analyses compared the relative risk of access complications between different sheath sizes, percutaneous access techniques, and indications for REBOA. Risk of bias was assessed using the Methodological Index for Non-Randomised Studies (MINORS) tool. Results: No randomised controlled trials were identified, and the overall study quality was poor. Twenty-eight studies including 887 adults were identified. REBOA was performed for trauma in 713 cases. The pooled proportion rate of vascular access complications was 8.6% (95% confidence interval 4.97 - 12.97), with substantial heterogeneity (I Conclusion: This updated meta-analysis aimed to be as comprehensive as possible considering the poor quality of source data and high risk of bias. It suggested that lower extremity vascular complications were higher than originally suspected after REBOA. While the technical aspects did not appear to impact the safety profile, a cautious association could be drawn between REBOA use for traumatic haemorrhage and a higher risk of arterial complications.
MeSH term(s)	Balloon Occlusion ; Hemorrhage/therapy ; Humans ; Lower Extremity/physiopathology ; Cardiovascular Diseases ; Aorta
Language	English
Publishing date	2023-02-14
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	1225869-6
ISSN	1532-2165 ; 1078-5884
ISSN (online)	1532-2165
ISSN	1078-5884
DOI	10.1016/j.ejvs.2023.02.007
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Article ; Online: A comparative analysis of tranexamic acid dosing strategies in traumatic major hemorrhage.

Gunn, Finn / Stevenson, Rheanna / Almuwallad, Ateeq / Rossetto, Andrea / Vulliamy, Paul / Brohi, Karim / Davenport, Ross

The journal of trauma and acute care surgery

2023 Volume 96, Issue 2, Page(s) 216–224

Abstract: Introduction: Tranexamic acid (TXA) is a life-saving treatment for traumatic hemorrhage, but the optimal dosing regimen remains unknown. Different doses and treatment strategies have been proposed, including single bolus, repeated bolus, or bolus plus ... ...

Abstract	Introduction: Tranexamic acid (TXA) is a life-saving treatment for traumatic hemorrhage, but the optimal dosing regimen remains unknown. Different doses and treatment strategies have been proposed, including single bolus, repeated bolus, or bolus plus infusion. The aim of this study was to determine the effect of different TXA dosing strategies on clinical outcomes in bleeding trauma patients. Methods: Secondary analysis of a perpetual cohort study from a UK Level I trauma center. Adult patients who activated the local major hemorrhage protocol and received TXA were included. The primary outcome was 28-day mortality. Secondary outcomes were 24-hour mortality, multiple organ dysfunction syndrome, venous thromboembolism, and rotational thromboelastometry fibrinolysis. Results: Over an 11-year period, 525 patients were included. Three dosing groups were identified: 1 g bolus only (n = 317), 1 g bolus +1 g infusion over 8 hours (n = 80), and 2 g bolus (n = 128). Demographics and admission physiology were similar, but there were differences in injury severity (median Injury Severity Score, 25, 29, and 25); and admission systolic blood pressure (median Systolic Blood Pressure, 99, 108, 99 mm Hg) across the 1-g, 1 g + 1 g, and 2-g groups. 28-day mortality was 21% in each treatment group. The incidence of multiple organ dysfunction syndrome was significantly higher in the bolus plus infusion group (84%) vs. 1 g bolus (64%) and 2 g bolus (62%) group, p = 0.002, but on multivariable analysis was nonsignificant. Venous thromboembolism rates were similar in the 1-g bolus (4%), 2 g bolus (8%) and bolus plus infusion groups (7%). There was no difference in rotational thromboelastometry maximum lysis at 24 hours: 5% in both the 1-g and 2-g bolus groups vs. 4% in bolus plus infusion group. Conclusion: Clinical outcomes and 24-hour fibrinolysis state were equivalent across three different dosing strategies of TXA. Single bolus administration is likely preferable to a bolus plus infusion regimen. Level of evidence: Therapeutic/Care Management; Level III.
MeSH term(s)	Adult ; Humans ; Tranexamic Acid/therapeutic use ; Antifibrinolytic Agents/therapeutic use ; Venous Thromboembolism/chemically induced ; Cohort Studies ; Multiple Organ Failure ; Hemorrhage/drug therapy ; Hemorrhage/etiology
Chemical Substances	Tranexamic Acid (6T84R30KC1) ; Antifibrinolytic Agents
Language	English
Publishing date	2023-10-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2651070-4
ISSN	2163-0763 ; 2163-0755
ISSN (online)	2163-0763
ISSN	2163-0755
DOI	10.1097/TA.0000000000004177
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Article ; Online: Immature platelet dynamics are associated with clinical outcomes after major trauma.

Schofield, Henry / Rossetto, Andrea / Armstrong, Paul C / Allan, Harriet E / Warner, Timothy D / Brohi, Karim / Vulliamy, Paul

Journal of thrombosis and haemostasis : JTH

2023 Volume 22, Issue 4, Page(s) 926–935

Abstract: Background: Major trauma results in dramatic changes in platelet behavior. Newly formed platelets are more reactive than older platelets, but their contributions to hemostasis and thrombosis after severe injury have not been previously evaluated.: ... ...

Abstract	Background: Major trauma results in dramatic changes in platelet behavior. Newly formed platelets are more reactive than older platelets, but their contributions to hemostasis and thrombosis after severe injury have not been previously evaluated. Objectives: To determine how immature platelet metrics and plasma thrombopoietin relate to clinical outcomes after major injury. Methods: A prospective observational cohort study was performed in adult trauma patients. Platelet counts and the immature platelet fraction (IPF) were measured at admission and 24 hours, 72 hours, and 7 days after injury. Thromboelastometry was performed at admission. Plasma thrombopoietin, c-Mpl, and GPIbα were quantified in a separate cohort. The primary outcome was in-hospital mortality; secondary outcomes were venous thromboembolic events and multiple organ dysfunction syndrome (MODS). Results: On admission, immature platelet counts (IPCs) were significantly lower in nonsurvivors (n = 40) than in survivors (n = 236; 7.3 × 10 Conclusion: Lower levels of immature platelets in the acute phase after major injury are associated with increased mortality, whereas higher immature platelet levels at later time points may predispose to thrombosis and MODS.
MeSH term(s)	Adult ; Humans ; Prospective Studies ; Thrombopoietin ; Venous Thromboembolism/diagnosis ; Blood Platelets ; Thrombosis
Chemical Substances	Thrombopoietin (9014-42-0)
Language	English
Publishing date	2023-12-13
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2023.12.002
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Article ; Online: Acute aorto-iliac and mesenteric arterial thromboses as presenting features of COVID-19.

Vulliamy, Paul / Jacob, Sabu / Davenport, Ross A

British journal of haematology

2020 Volume 189, Issue 6, Page(s) 1053–1054

MeSH term(s)	Aged ; Aorta/diagnostic imaging ; Aorta/surgery ; Arterial Occlusive Diseases/blood ; Arterial Occlusive Diseases/diagnostic imaging ; Arterial Occlusive Diseases/etiology ; Arterial Occlusive Diseases/surgery ; Betacoronavirus ; COVID-19 ; Computed Tomography Angiography ; Coronavirus Infections/blood ; Coronavirus Infections/complications ; Coronavirus Infections/diagnostic imaging ; Coronavirus Infections/surgery ; Humans ; Iliac Artery/diagnostic imaging ; Iliac Artery/surgery ; Male ; Mesenteric Arteries/diagnostic imaging ; Mesenteric Arteries/surgery ; Middle Aged ; Pandemics ; Pneumonia, Viral/blood ; Pneumonia, Viral/complications ; Pneumonia, Viral/diagnostic imaging ; Pneumonia, Viral/surgery ; SARS-CoV-2 ; Thrombectomy ; Thrombosis/blood ; Thrombosis/diagnostic imaging ; Thrombosis/etiology ; Thrombosis/surgery
Keywords	covid19
Language	English
Publishing date	2020-05-15
Publishing country	England
Document type	Case Reports ; Letter
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.16760
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