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Article ; Online: Fibrinolysis and antifibrinolytic treatment in the trauma patient.

Gall, Lewis S / Davenport, Ross A

2018 Volume 31, Issue 2, Page(s) 227–233

Abstract: Purpose of review: The role of antifibrinolytics in trauma haemorrhage and early coagulopathy remains controversial with respect to patient selection, dosage, timing of treatment, and risk of thrombotic complications. This review presents our current ... ...

Abstract	Purpose of review: The role of antifibrinolytics in trauma haemorrhage and early coagulopathy remains controversial with respect to patient selection, dosage, timing of treatment, and risk of thrombotic complications. This review presents our current understanding of the mechanisms of fibrinolysis in trauma, diagnostic evaluation, and the evidence base for treatment. Recent findings: Excessive fibrinolysis following severe injury is a major component of acute traumatic coagulopathy and contributes to the high mortality from trauma haemorrhage. The protein C pathway, endothelial dysfunction, platelet activity, shock, and tissue injury are key to the development of hyper fibrinolysis in trauma. D-dimer and viscoelastic haemostatic assays (rotational thromboelastometry, TEG) remain the best available diagnostic modalities but have a number of limitations compared with plasma biomarkers of fibrinolytic activation, for example, plasmin-α2-antiplasmin complex. Current evidence supports the continued empiric use of tranexamic acid in major trauma haemorrhage. Summary: Improving the outcomes for bleeding trauma patients requires a deeper understanding of the mechanisms driving hyperfibrinolysis and the subsequent switch toward a prothrombotic state. Discovering the interplay between platelet activity, fibrinogen utilization, the immune response, and the fibrinolytic system may lead to development of novel therapeutics.
MeSH term(s)	Antifibrinolytic Agents/therapeutic use ; Blood Coagulation Disorders/blood ; Blood Coagulation Disorders/drug therapy ; Blood Coagulation Disorders/etiology ; Blood Coagulation Disorders/physiopathology ; Blood Coagulation Tests ; Critical Care/methods ; Critical Care/standards ; Fibrinolysis/drug effects ; Fibrinolysis/physiology ; Hemorrhage/blood ; Hemorrhage/drug therapy ; Hemorrhage/etiology ; Hemorrhage/physiopathology ; Humans ; Patient Selection ; Practice Guidelines as Topic ; Thrombosis/blood ; Thrombosis/chemically induced ; Thrombosis/physiopathology ; Thrombosis/prevention & control ; Time Factors ; Treatment Outcome ; Wounds and Injuries/blood ; Wounds and Injuries/complications ; Wounds and Injuries/physiopathology
Chemical Substances	Antifibrinolytic Agents
Language	English
Publishing date	2018-01-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645203-6
ISSN	1473-6500 ; 0952-7907
ISSN (online)	1473-6500
ISSN	0952-7907
DOI	10.1097/ACO.0000000000000561
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Article ; Online: Choledocholithiasis: Long-term follow-up in patients without stone clearance at first endoscopic retrograde cholangiopancreatography.

Kourounis, Georgios / Gall, Lewis S / McArthur, Donald / Gibson, Simon / Glen, Paul

Journal of digestive diseases

2021 Volume 22, Issue 9, Page(s) 551–556

Abstract: Objectives: Complete clearance during endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis is not always successful and biliary stenting is commonplace. Strategies vary between temporary stent placement (TSP) with interval ERCP ... ...

Abstract	Objectives: Complete clearance during endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis is not always successful and biliary stenting is commonplace. Strategies vary between temporary stent placement (TSP) with interval ERCP or permanent stent placement (PSP) and watchful waiting for recurrent biliary obstruction (RBO). This study aimed to describe outcomes in these two groups and stent patency rates in PSP. Methods: Patients with incomplete clearance at first ERCP for choledocholithiasis between May 2015 and December 2018 were identified. Clinical outcomes were obtained by retrospective interrogation of the case notes. Median follow-up duration was 41 months (interquartile range 29-51 mo). Results: Of 1263 index ERCP, 199 (15.8%) had no stone clearance, with 53.3% receiving PSP and 46.7% undergoing TSP. The TSP group had repeat ERCP after a median of 8 weeks; 75.3% had clearance on a repeat ERCP. The PSP group was elder than the TSP group (82 y vs 72 y, P < 0.001). The rates of RBO (32.1% vs 16.1%) and emergency readmissions (32.1% vs 19.4%) were higher in the PSP group (both P < 0.05). More patients died without further biliary disease in the PSP group (39.6% vs 12.9%, P = 0.001). PSP stent patency rates at 6, 12, 24, 36, and 61 months were 87.7%, 82.1%, 75.5%, 69.8% and 67.9%, respectively. Conclusions: Though PSP had higher RBO and emergency readmissions, two-thirds of patients either died or survived without recurrent biliary disease. Stent patency decreased fastest in the first 12 months. Criteria to guide decision-making for biliary stenting remain unclear.
MeSH term(s)	Aged ; Cholangiopancreatography, Endoscopic Retrograde ; Choledocholithiasis/diagnostic imaging ; Choledocholithiasis/surgery ; Cholestasis ; Follow-Up Studies ; Humans ; Retrospective Studies ; Stents ; Treatment Outcome
Language	English
Publishing date	2021-09-16
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2317117-0
ISSN	1751-2980 ; 1751-2972
ISSN (online)	1751-2980
ISSN	1751-2972
DOI	10.1111/1751-2980.13043
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Article ; Online: Response to the Comment on "The S100A10 Pathway Mediates an Occult Hyperfibrinolytic Subtype in Trauma Patients".

Gall, Lewis S / Vulliamy, Paul / Brohi, Karim / Davenport, Ross A

Annals of surgery

2019 Volume 271, Issue 4, Page(s) e111–e112

MeSH term(s)	Blood Coagulation Disorders ; Humans
Language	English
Publishing date	2019-12-03
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	340-2
ISSN	1528-1140 ; 0003-4932
ISSN (online)	1528-1140
ISSN	0003-4932
DOI	10.1097/SLA.0000000000003691
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Article ; Online: Diagnosis and Treatment of Hyperfibrinolysis in Trauma (A European Perspective).

Gall, Lewis S / Brohi, Karim / Davenport, Ross A

Seminars in thrombosis and hemostasis

2017 Volume 43, Issue 2, Page(s) 224–234

Abstract: Fibrinolysis activation occurs almost universally after severe trauma. Systemic hyperfibrinolysis is a key component of acute traumatic coagulopathy and associated with poor clinical outcomes, although controversy exists over optimal treatment strategies. ...

Abstract	Fibrinolysis activation occurs almost universally after severe trauma. Systemic hyperfibrinolysis is a key component of acute traumatic coagulopathy and associated with poor clinical outcomes, although controversy exists over optimal treatment strategies. The mechanistic drivers and dynamics of fibrinolytic activation in response to injury and trauma resuscitation are currently unclear. Furthermore, therapeutic triggers are compounded by the lack of a sensitive and rapid diagnostic tool, with discrepancy between hyperfibrinolysis diagnosed by viscoelastic hemostatic assays versus biomarkers for fibrinolysis. Rotational thromboelastometry and thromboelastography appear capable of detecting the severest forms of hyperfibrinolysis but are relatively insensitive to moderate, yet clinically significant fibrinolytic activation. Rapid evaluation of the current status of the fibrinolytic system remains a challenge and therefore the decision whether to administer an antifibrinolytic agent should be based on available evidence from clinical trials. In line with current European guidelines, we recommend that all bleeding trauma patients, and in particular, severely injured patients with evidence of hemorrhagic shock, should receive early empiric tranexamic acid. This review explains our current knowledge of the pathophysiological pathways which induce hyperfibrinolysis in trauma hemorrhage, evaluates the available diagnostic modalities, and describes current treatment strategies.
MeSH term(s)	Fibrinolysis/physiology ; Humans ; Wounds and Injuries/blood ; Wounds and Injuries/drug therapy
Language	English
Publishing date	2017-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0036-1598001
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Article ; Online: Diagnosis, treatment, and outcome of patients with oesophagogastric cancer during the COVID-19 pandemic: national study.

Baxter, Mark A / Khan, Khurram S / Gall, Lewis S / Samuelson, Catherine / McCollum, Catherine / Chuntamongkol, Rongkagorn / Narramneni, Lakshmi R / Al-Zuabi, Manaf / Bryce, Gavin / Shareef, Hala E J / Forshaw, Matthew / Petty, Russell D

The British journal of surgery

2023 Volume 110, Issue 4, Page(s) 456–461

Abstract: Background: The national response to COVID-19 has had a significant impact on cancer services. This study investigated the effect of national lockdown on diagnosis, management, and outcomes of patients with oesophagogastric cancers in Scotland.: ... ...

Abstract	Background: The national response to COVID-19 has had a significant impact on cancer services. This study investigated the effect of national lockdown on diagnosis, management, and outcomes of patients with oesophagogastric cancers in Scotland. Methods: This retrospective cohort study included consecutive new patients presenting to regional oesophagogastric cancer multidisciplinary teams in National Health Service Scotland between October 2019 and September 2020. The study interval was divided into before and after lockdown, based on the first UK national lockdown. Electronic health records were reviewed and results compared. Results: Some 958 patients with biopsy-proven oesophagogastric cancer in 3 cancer networks were included: 506 (52.8 per cent) before and 452 (47.2 per cent) after lockdown. Median age was 72 (range 25-95) years and 630 patients (65.7 per cent) were men. There were 693 oesophageal (72.3 per cent) and 265 gastric (27.7 per cent) cancers. Median time to gastroscopy was 15 (range 0-337) days before versus 19 (0-261) days after lockdown (P < 0.001). Patients were more likely to present as an emergency after lockdown (8.5 per cent before versus 12.4 per cent after lockdown; P = 0.005), had poorer Eastern Cooperative Oncology group performance status, were more symptomatic, and presented with a higher stage of disease (stage IV: 49.8 per cent before versus 58.8 per cent after lockdown; P = 0.04). There was a shift to treatment with non-curative intent (64.6 per cent before versus 77.4 per cent after lockdown; P < 0.001). Median overall survival was 9.9 (95 per cent c.i. 8.7 to 11.4) months before and 6.9 (5.9 to 8.3) months after lockdown (HR 1.26, 95 per cent c.i. 1.09 to 1.46; P = 0.002). Conclusion: This national study has highlighted the adverse impact of COVID-19 on oesophagogastric cancer outcomes in Scotland. Patients presented with more advanced disease and a shift towards treatment with non-curative intent was observed, with a subsequent negative impact on overall survival.
MeSH term(s)	Male ; Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Female ; COVID-19/epidemiology ; Retrospective Studies ; Pandemics ; State Medicine ; Stomach Neoplasms/diagnosis ; Stomach Neoplasms/epidemiology ; Stomach Neoplasms/therapy ; Esophageal Neoplasms/diagnosis ; Esophageal Neoplasms/epidemiology ; Esophageal Neoplasms/therapy ; Communicable Disease Control ; COVID-19 Testing
Language	English
Publishing date	2023-02-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2985-3
ISSN	1365-2168 ; 0263-1202 ; 0007-1323 ; 1355-7688
ISSN (online)	1365-2168
ISSN	0263-1202 ; 0007-1323 ; 1355-7688
DOI	10.1093/bjs/znad003
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Article ; Online: Stage migration in newly diagnosed oesophagogastric cancer during the first wave of the COVID-19 pandemic.

Khan, Khurram S / Gall, Lewis S / Dreyer, Stephan / McCollum, Catherine / Chuntamongkol, Rongkagorn / Craig, Carol / MacKay, Colin / Macdonald, Andrew / Forshaw, Matthew

The British journal of surgery

2022 Volume 109, Issue 8, Page(s) 773–774

MeSH term(s)	COVID-19/epidemiology ; Humans ; Neoplasms ; Pandemics
Language	English
Publishing date	2022-05-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2985-3
ISSN	1365-2168 ; 0263-1202 ; 0007-1323 ; 1355-7688
ISSN (online)	1365-2168
ISSN	0263-1202 ; 0007-1323 ; 1355-7688
DOI	10.1093/bjs/znac112
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Article: Diagnosis and Treatment of Hyperfibrinolysis in Trauma (A European Perspective)

Gall, Lewis S. / Brohi, Karim / Davenport, Ross A.

Seminars in Thrombosis and Hemostasis

(Fibrinolysis: Biochemistry, Clinical Aspects, and Therapeutic Potential)

2017 Volume 43, Issue 02, Page(s) 224–234

Series title	Fibrinolysis: Biochemistry, Clinical Aspects, and Therapeutic Potential
Abstract	Fibrinolysis activation occurs almost universally after severe trauma. Systemic hyperfibrinolysis is a key component of acute traumatic coagulopathy and associated with poor clinical outcomes, although controversy exists over optimal treatment strategies. The mechanistic drivers and dynamics of fibrinolytic activation in response to injury and trauma resuscitation are currently unclear. Furthermore, therapeutic triggers are compounded by the lack of a sensitive and rapid diagnostic tool, with discrepancy between hyperfibrinolysis diagnosed by viscoelastic hemostatic assays versus biomarkers for fibrinolysis. Rotational thromboelastometry and thromboelastography appear capable of detecting the severest forms of hyperfibrinolysis but are relatively insensitive to moderate, yet clinically significant fibrinolytic activation. Rapid evaluation of the current status of the fibrinolytic system remains a challenge and therefore the decision whether to administer an antifibrinolytic agent should be based on available evidence from clinical trials. In line with current European guidelines, we recommend that all bleeding trauma patients, and in particular, severely injured patients with evidence of hemorrhagic shock, should receive early empiric tranexamic acid. This review explains our current knowledge of the pathophysiological pathways which induce hyperfibrinolysis in trauma hemorrhage, evaluates the available diagnostic modalities, and describes current treatment strategies.
Keywords	trauma ; fibrinolysis ; hemorrhage ; coagulopathy ; tranexamic acid
Language	English
Publishing date	2017-02-20
Publisher	Thieme Medical Publishers
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	196901-8
ISSN	1098-9064 ; 0094-6176
ISSN (online)	1098-9064
ISSN	0094-6176
DOI	10.1055/s-0036-1598001
Database	Thieme publisher's database

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Article ; Online: Platelet transfusions reduce fibrinolysis but do not restore platelet function during trauma hemorrhage.

Vulliamy, Paul / Gillespie, Scarlett / Gall, Lewis S / Green, Laura / Brohi, Karim / Davenport, Ross A

The journal of trauma and acute care surgery

2017 Volume 83, Issue 3, Page(s) 388–397

Abstract: Background: Platelets play a critical role in hemostasis with aberrant function implicated in trauma-induced coagulopathy. However, the impact of massive transfusion protocols on platelet function during trauma hemorrhage is unknown. The aim of this ... ...

Abstract	Background: Platelets play a critical role in hemostasis with aberrant function implicated in trauma-induced coagulopathy. However, the impact of massive transfusion protocols on platelet function during trauma hemorrhage is unknown. The aim of this study was to characterize the effects of platelet transfusion on platelet aggregation and fibrinolytic markers during hemostatic resuscitation. Methods: Trauma patients enrolled into the prospective Activation of Coagulation and Inflammation in Trauma study between January 2008 and November 2015 who received at least four units of packed red blood cells (PRBCs) were included. Blood was drawn in the emergency department within 2 hours of injury and at intervals after every four units of PRBCs transfused. Platelet aggregation was assessed in whole blood with multiple electrode aggregometry. Plasma proteins were quantified by enzyme-linked immunosorbent assay. Results: Of 161 patients who received four or more PRBCs as part of their initial resuscitation, 44 received 8 to 11 units and 28 received 12 units or more. At each timepoint during bleeding, platelet aggregation was similar in patients who had received a platelet transfusion compared with those who had only received other blood products (p > 0.05 for all timepoints). Platelet transfusion during the four PRBC intervals was associated with a decrease in maximum lysis on rotational thromboelastometry (start of interval, 6% [2-12] vs. end of interval, 2% [0-5]; p = 0.001), an increase in plasminogen activator inhibitor-1 (start of interval, 35.9 ± 14.9 vs. end of interval, 66.7 ± 22.0; p = 0.007) and a decrease in tissue plasminogen activator (start of interval, 26.2 ± 10.5 vs. end of interval, 19.0 +/- 5.1; p = 0.04). No statistically significant changes in these parameters occurred in intervals which did not contain platelets. Conclusion: Current hemostatic resuscitation strategies do not appear to restore platelet aggregation during active hemorrhage. However, stored platelets may attenuate fibrinolysis by providing an additional source of plasminogen activator inhibitor-1. Further investigation into the effects of early platelet transfusion on platelet function, hemostatic, and clinical outcomes during bleeding are warranted. Level of evidence: Therapeutic, level III.
MeSH term(s)	Adult ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibrinolysis/physiology ; Hemorrhage/therapy ; Hemostasis/physiology ; Humans ; Male ; Middle Aged ; Platelet Aggregation ; Platelet Function Tests ; Platelet Transfusion ; Prospective Studies ; Resuscitation/methods ; Thrombelastography ; Wounds and Injuries/complications
Language	English
Publishing date	2017-04-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2651070-4
ISSN	2163-0763 ; 2163-0755
ISSN (online)	2163-0763
ISSN	2163-0755
DOI	10.1097/TA.0000000000001520
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Article ; Online: The S100A10 Pathway Mediates an Occult Hyperfibrinolytic Subtype in Trauma Patients.

Gall, Lewis S / Vulliamy, Paul / Gillespie, Scarlett / Jones, Timothy F / Pierre, Rochelle S J / Breukers, Sabine E / Gaarder, Christine / Juffermans, Nicole P / Maegele, Marc / Stensballe, Jakob / Johansson, Pär I / Davenport, Ross A / Brohi, Karim

Annals of surgery

2019 Volume 269, Issue 6, Page(s) 1184–1191

Abstract: Objective: To determine the characteristics of trauma patients with low levels of fibrinolysis as detected by viscoelastic hemostatic assay (VHA) and explore the underlying mechanisms of this subtype.: Background: Hyperfibrinolysis is a central ... ...

Abstract	Objective: To determine the characteristics of trauma patients with low levels of fibrinolysis as detected by viscoelastic hemostatic assay (VHA) and explore the underlying mechanisms of this subtype. Background: Hyperfibrinolysis is a central component of acute traumatic coagulopathy but a group of patients present with low levels of VHA-detected fibrinolysis. There is concern that these patients may be at risk of thrombosis if empirically administered an antifibrinolytic agent. Methods: A prospective multicenter observational cohort study was conducted at 5 European major trauma centers. Blood was drawn on arrival, within 2 hours of injury, for VHA (rotation thromboelastometry [ROTEM]) and fibrinolysis plasma protein analysis including the fibrinolytic mediator S100A10. An outcomes-based threshold for ROTEM hypofibrinolysis was determined and patients grouped by this and by D-dimer (DD) levels. Results: Nine hundred fourteen patients were included in the study. The VHA maximum lysis (ML) lower threshold was determined to be <5%. Heterogeneity existed among patients with low ML, with survivors sharing similar clinical and injury characteristics to patients with normal ML values (5-15%). Those who died were critically injured with a preponderance of traumatic brain injury and had a 7-fold higher DD level (died vs. survived: 103,170 vs. 13,672 ng/mL, P < 0.001). Patients with low ML and high DD demonstrated a hyperfibrinolytic biomarker profile, low tissue plasminogen activator levels but high plasma levels of S100A10. S100A10 was negatively correlated with %ML (r = -0.26, P < 0.001) and caused a significant reduction in %ML when added to whole blood ex-vivo. Conclusions: Patients presenting with low ML and low DD levels have low injury severity and normal outcomes. Conversely, patients with low ML but high DD levels are severely injured, functionally coagulopathic and have poor clinical outcomes. These patients have low tissue plasminogen activator levels and are not detectable by ROTEM. S100A10 is a cell surface plasminogen receptor which may drive the hyperfibrinolysis in these patients and which when shed artificially lowers %ML ex-vivo.
MeSH term(s)	Adult ; Aged ; Annexin A2/blood ; Blood Coagulation Factors/metabolism ; Female ; Fibrin Fibrinogen Degradation Products/metabolism ; Fibrinolysis/physiology ; Humans ; Male ; Middle Aged ; Prospective Studies ; S100 Proteins/blood ; Survival Rate ; Thrombelastography ; Wounds and Injuries/blood ; Wounds and Injuries/complications ; Wounds and Injuries/mortality ; Young Adult
Chemical Substances	Annexin A2 ; Blood Coagulation Factors ; Fibrin Fibrinogen Degradation Products ; S100 Proteins ; S100 calcium binding protein A10 ; fibrin fragment D
Language	English
Publishing date	2019-05-16
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	340-2
ISSN	1528-1140 ; 0003-4932
ISSN (online)	1528-1140
ISSN	0003-4932
DOI	10.1097/SLA.0000000000002733
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