Observational studyThe journal of trauma and acute care surgery2017
Fibrinolysis shutdown is associated with a fivefold increase in mortality in trauma patients lacking hypersensitivity to tissue plasminogen activator.
Observational study in The journal of trauma and acute care surgery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 101 citations in OpenAlex.
- The abnormal coagulation status in endometriosis patients: a systematic review and meta-analysis.Journal of thrombosis and thrombolysis · 2026Pooled it
- Inhospital coagulation management and fluid replacement therapy in patients with multiple and/or severe injuries - a systematic review and clinical practice guideline update.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2025Pooled it
- Fibrinolysis Resistance After Injury Is a Risk Factor for a Hospital-Acquired Pneumonia-Like Disease Pattern.Surgical infections · 2024Trial
- Hemostatic abnormalities after trauma resuscitation: challenges and strategies in caring for the critically injured patient.Annals of intensive care · 2025Review
- Tranexamic acid: a narrative review of its current role in perioperative medicine and acute medical bleeding.Frontiers in medicine · 2024Review
- The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment.International journal of molecular sciences · 2023Review
- Fibrinolysis Shutdown and Hypofibrinolysis Are Not Synonymous Terms: The Clinical Significance of Differentiating Low Fibrinolytic States.Seminars in thrombosis and hemostasis · 2023Review
- Hemorrhagic shock and tissue injury provoke distinct components of trauma-induced coagulopathy in a swine model.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2023Article
- Point-of-care diagnosis and monitoring of fibrinolysis resistance in the critically ill: results from a feasibility study.Critical care (London, England) · 2023Article
- Fibrinolysis resistance after liver transplant as a predictor of early infection.American journal of surgery · 2022Article
- Proteomics of Coagulopathy Following Injury Reveals Limitations of Using Laboratory Assessment to Define Trauma-Induced Coagulopathy to Predict Massive Transfusion.Annals of surgery open : perspectives of surgical history, education, and clinical approaches · 2022Article
- Inhalation Injury Is Associated With Endotheliopathy and Abnormal Fibrinolytic Phenotypes in Burn Patients: A Cohort Study.Journal of burn care & research : official publication of the American Burn Association · 2022Article
- Fibrinolytic system activation immediately following trauma was quickly and intensely suppressed in a rat model of severe blunt trauma.Scientific reports · 2021Article
- Clot Retraction: Cellular Mechanisms and Inhibitors, Measuring Methods, and Clinical Implications.Biomedicines · 2021Review
- Euglobulin clot lysis time reveals a high frequency of fibrinolytic activation in trauma.Thrombosis research · 2021Article
- Fibrinolysis Shutdown in COVID-19: Clinical Manifestations, Molecular Mechanisms, and Therapeutic Implications.Journal of the American College of Surgeons · 2021Review
- Trauma-induced coagulopathy.Nature reviews. Disease primers · 2021Review
- Review
- Glycocalyx components affect platelet function, whole blood coagulation, and fibrinolysis: an in vitro study suggesting a link to trauma-induced coagulopathy.BMC anesthesiology · 2021Article
- Early abnormal fibrinolysis and mortality in patients with thermal injury: a prospective cohort study.BJS open · 2021Observational
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundFibrinolysis shutdown (SD) is an independent risk factor for increased mortality in trauma. High levels of plasminogen activator inhibitor-1 (PAI-1) directly binding tissue plasminogen activator (t-PA) is a proposed mechanism for SD; however, patients with low PAI-1 levels present to the hospital with a rapid TEG (r-TEG) LY30 suggestive SD. We therefore hypothesized that two distinct phenotypes of SD exist, one, which is driven by t-PA inhibition, whereas another is due to an inadequate t-PA release in response to injury.
methodsTrauma activations from our Level I center between 2014 and 2016 with blood collected within an hour of injury were analyzed with r-TEG and a modified TEG assay to quantify fibrinolysis sensitivity using exogenous t-PA (t-TEG). Using the existing r-TEG thresholds for SD (<0.9%), physiologic (LY30 0.9-2.9%), and hyperfibrinolysis (LY30 > 2.9%) patients were stratified into phenotypes. A t-TEG LY30 greater than 95th percentile of healthy volunteers (n = 140) was classified as t-PA hypersensitive and used to subdivide phenotypes. A nested cohort had t-PA and PAI-1 activity levels measured in addition to proteomic analysis of additional fibrinolytic regulators.
resultsThis study included 398 patients (median New Injury Severity Score, 18), t-PA-Sen was present in 27% of patients. Shutdown had the highest mortality rate (20%) followed by hyperfibinolysis (16%) and physiologic (9% p = 0.020). In the non-t-PA hypersensitive cohort, SD had a fivefold increase in mortality (15%) compared with non-SD patients (3%; p = 0.003) which remained significant after adjusting for Injury Severity Score and age (p = 0.033). Overall t-PA activity (p = 0.002), PAI-1 (p < 0.001), and t-PA/PAI-1 complex levels (p = 0.006) differed between the six phenotypes, and 54% of fibrinolytic regulator proteins analyzed (n = 19) were significantly different.
conclusionIn conclusion, acute fibrinolysis SD is not caused by a single etiology, and is clearly associated with PAI-1 activity. The differential phenotypes require an ongoing investigation to identify the optimal resuscitation strategy for these patients. LEVEL OF EVIDENCE: Prognostic, level III.
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