The S100A10 Pathway Mediates an Occult Hyperfibrinolytic Subtype in Trauma Patients

Gall, Lewis; 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; Brohi, Karim

doi:10.1097/sla.0000000000002733

Cited by 86 publications

(78 citation statements)

References 27 publications

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“…We acknowledge that Li60 would be useful in addition to Li30 in the assessment of fibrinolysis; however, the throughput of casualties in the hospital meant that often ROTEM machines were required for further clinical analysis, and so, as per hospital protocols, analysis was stopped after Li30 was reached. Poor sensitivity to fibrinolysis has been demonstrated before in civilian trauma, and Gall et al suggested that soluble S100A10 maybe interfering with ROTEM analysis of fibrinolysis. Our results suggest further studies of thromboelastography in military trauma are required.…”

Section: Discussionmentioning

confidence: 95%

“…Second, there may be other mechanisms of activation of plasminogen during traumatic injury. For example, Gall et al suggests that a plasminogen receptor S100A10 is released from the endothelium during trauma and may be independently activating fibrinolysis. Whatever the mechanism, our data show that fibrinolysis is prevalent in severely injured military casualties and that there was greater fibrinolytic activation with BLAST and GSWs, which most likely accounts for the effectiveness of TXA in reducing trauma and hemorrhage mortality in this population …”

Section: Discussionmentioning

confidence: 99%

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A prospective observational study of acute traumatic coagulopathy in traumatic bleeding from the battlefield

et al. 2020

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BACKGROUND Acute trauma coagulopathy (ATC) after military trauma has not been comprehensively studied. ATC is defined as a prolonged prothrombin time ratio (PTr) or reduced clot amplitude (A5) in viscoelastic testing. Compared to civilian trauma, military trauma has more injuries from explosions and gunshot wounds (GSWs), potentially leading to a different pathophysiology for traumatic coagulopathy. This study aimed to characterize military ATC on admission to a military hospital in Afghanistan and to explore any differences due to the mechanism of injury. METHODS Severely injured military casualties were enrolled in the study. Blood samples were taken on admission and after routine testing, waste plasma was prepared, frozen, and transported to the United Kingdom for in‐depth hemostatic analysis. RESULTS Seventy‐seven percent of casualties had ATC defined by a PTr greater than 1.2 and 19% when defined by rotational thromboelastometry (ROTEM) A5 less than 36 mm. Coagulation factor depletion correlated with degree of shock, particularly factor V (p < 0.01), factor X (p < 0.01), and fibrinogen levels (p < 0.01). Thrombin generation was well preserved. Fibrinolytic biomarkers were raised correlating with the degree of shock (p < 0.01), and 8% of casualties had hyperfibrinolysis on ROTEM analysis. Plasmin‐antiplasmin complexes (p < 0.01) and d‐dimer levels (p = 0.01) were higher and clot firmness lower (p = 0.02) in those injured by explosion compared to GSW's. CONCLUSIONS ATC was present and correlated with shock, similar to civilian trauma. Thrombin generation remained adequate. Fibrinogen and factor V levels were disproportionately low but still sufficient to allow clot formation. Fibrinolysis is a key feature, probably due to a tissue plasminogen activator surge at the time of injury. Blast injuries are associated with a greater activation of fibrinolysis than GSWs.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

A prospective observational study of acute traumatic coagulopathy in traumatic bleeding from the battlefield

et al. 2020

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“…Recent studies have focused on hypofibrinolysis (fibrinolytic shutdown, SD), demonstrating that SD is the most common fibrinolytic state in severe trauma patients and that the mortality rate in such patients is higher than that in patients in a physiologic fibrinolytic state 27,28 . There is concern surrounding the increases in mortality rate and frequency of thrombotic complications when TXA is administered to patients with SD who are already in a hypofibrinolytic state 18,29 . Furthermore, unlike the CRASH trial, in which the use of TXA was emphasized, opposing results were observed in clinical research studies,in which the use of TXA Table 3.…”

Section: Discussionmentioning

confidence: 99%

FIBTEM Improves the Sensitivity of Hyperfibrinolysis Detection in Severe Trauma Patients: A Retrospective Study Using Thromboelastometry

Wang

Park

Bae

et al. 2020

Sci Rep

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Rotational thromboelastometry (ROTEM) can only detect high-degree hyperfibrinolysis (HF), despite being frequently used in trauma patients. We investigated whether considering FIBTEM HF (the presence of maximal lysis (ML) > 15%) could increase ROTEM-based HF detection's sensitivity. This observational cohort study was performed at a level 1 trauma centre. Trauma patients with an Injury Severity Score (ISS) > 15 who underwent ROTEM in the emergency department between 2016 and 2017 were included. EXTEM HF was defined as ML > 15% in EXTEM. We compared mortality rates between EXTEM HF, FIBTEM HF, and non-HF patient groups. Overall, 402 patients were included, of whom 45% were men (mean age, 52.5 years; mean ISS, 27). The EXTEM HF (n = 37), FIBTEM HF (n = 132), and non-HF (n = 233) groups had mortality rates of 81.1%, 22.3%, and 10.3%, respectively. The twofold difference in mortality rates between the FIBTEM HF and non-HF groups remained statistically significant after Bonferroni correction (P = 0.01). On multivariable Cox regression analysis, FIBTEM HF was independently associated with in-hospital mortality (adjusted hazard ratio 2.15, 95% confidence interval 1.21-3.84, P = 0.009). Here, trauma patients with FIBTEM HF had significantly higher mortality rates than those without HF. FIBTEM be a valuable diagnostic method to improve HF detection's sensitivity in trauma patients.

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“…The parameters for the definition of fibrinolytic shutdown as determined by VETs and used to guide BCT in bleeding patients recently have been refined and are matters of continued investigation. 25,[142][143][144][145][146][147] As has been studied in trauma and liver transplant patients, it would be reasonable to infer that a similar fibrinolytic spectrum exists in cancer patients; there are theoretical and clinical studies that confirm this inference. In fact, there has been a significant body of work regarding the fibrinolytic system and cancer.…”

Section: The Spectrum Of Macmentioning

confidence: 99%

Use of Viscoelastography in Malignancy-Associated Coagulopathy and Thrombosis: A Review

Walsh

Moore

et al. 2019

Semin Thromb Hemost

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The relationship between malignancy and coagulopathy is one that is well documented yet incompletely understood. Clinicians have attempted to quantify the hypercoagulable state produced in various malignancies using common coagulation tests such as prothrombin time, activated partial thromboplastin time, and platelet count; however, due to these tests' focus on individual aspects of coagulation during one specific time point, they have failed to provide clinicians the complete picture of malignancy-associated coagulopathy (MAC). Viscoelastic tests (VETs), such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM), are whole blood analyses that have the advantage of providing information related to the cumulative effects of plasma clotting factors, platelets, leukocytes, and red cells during all stages of the coagulation and fibrinolytic processes. VETs have gained popularity in the care of trauma patients to objectively measure trauma-induced coagulopathy (TIC), but the utility of VETs remains yet unrealized in many other medical specialties. The authors discuss the similarities and differences between TIC and MAC, and propose a mechanism for the hypercoagulable state of MAC that revolves around the thrombomodulin–thrombin complex as it switches between activating the protein C anticoagulation pathway or the thrombin activatable fibrinolysis inhibitor coagulation pathway. Additionally, they review the current literature on the use of TEG and ROTEM in patients with various malignancies. Although limited research is currently available, early results demonstrate the utility of both TEG and ROTEM in the prediction of hypercoagulable states and thromboembolic complications in oncologic patients.

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The S100A10 Pathway Mediates an Occult Hyperfibrinolytic Subtype in Trauma Patients

Cited by 86 publications

References 27 publications

A prospective observational study of acute traumatic coagulopathy in traumatic bleeding from the battlefield

A prospective observational study of acute traumatic coagulopathy in traumatic bleeding from the battlefield

FIBTEM Improves the Sensitivity of Hyperfibrinolysis Detection in Severe Trauma Patients: A Retrospective Study Using Thromboelastometry

Use of Viscoelastography in Malignancy-Associated Coagulopathy and Thrombosis: A Review

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