Observational studyThe journal of trauma and acute care surgery2020
Dense and dangerous: The tissue plasminogen activator-resistant fibrinolysis shutdown phenotype is due to abnormal fibrin polymerization.
Observational study in The journal of trauma and acute care surgery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Assays to quantify fibrinolysis: strengths and limitations. Communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee on fibrinolysis.Journal of thrombosis and haemostasis : JTH · 2023Guideline
- Connecting impaired fibrinolysis and dyslipidemia.Research and practice in thrombosis and haemostasis · 2024Article
- Fibrinolysis resistance after liver transplant as a predictor of early infection.American journal of surgery · 2022Article
- Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy.The journal of trauma and acute care surgery · 2022Article
- Trauma-induced pulmonary thromboembolism: What's update?Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2022Review
- Increased histone-DNA complexes and endothelial-dependent thrombin generation in severe COVID-19.Vascular pharmacology · 2022Article
- COVID-19 patient plasma demonstrates resistance to tPA-induced fibrinolysis as measured by thromboelastography.Journal of thrombosis and thrombolysis · 2021Article
- Actin is associated with tissue injury in trauma patients and produces a hypercoagulable profile in vitro.The journal of trauma and acute care surgery · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundBoth hyperfibrinolysis and fibrinolysis shutdown can occur after severe trauma. The subgroup of trauma patients with fibrinolysis shutdown resistant to tissue plasminogen activator (t-PA)-mediated fibrinolysis have increased mortality. Fibrin polymerization and structure may influence fibrinolysis subgroups in trauma, but fibrin architecture has not been characterized in acutely injured subjects. We hypothesized that fibrin polymerization measured in situ will correlate with fibrinolysis subgroups.
methodsBlood samples were collected from trauma patients and noninjured controls. We selected samples across a range of fibrinolysis phenotypes (shutdown, physiologic, hyperfibrinolysis) and t-PA sensitivities (sensitive, physiologic, resistant) determined by thrombelastography. Plasma clots were created in situ with fluorescent fibrinogen and imaged using confocal microscopy for analysis of clot architecture in three dimensions. For each clot, we quantified the fiber resolvability, a metric of fiber distinctness or clarity, by mapping the variance of fluorescence intensity relative to background fluorescence. We also determined clot porosity by measuring the size and distribution of the gaps between fibrin fibers in three-dimensional space. We compared these measures across fibrinolysis subgroups.
resultsFiber resolvability was significantly lower in all trauma subgroups compared with controls (n = 35 and 5, respectively; p < 0.05). We observed markedly different patterns of fibrin architecture among trauma patients stratified by fibrinolysis subgroup. Subjects with t-PA-resistant fibrinolysis shutdown exhibited abnormal, densely packed fibrin clots nearly devoid of pores. Individuals with t-PA-hypersensitive fibrinolysis shutdown had highly irregular clots with pores as large as 2500 μm to 20,000 μm, versus 78 μm to 1250 μm in noninjured controls.
conclusionFiber resolvability was significantly lower in trauma patients than controls, and subgroups of fibrinolysis differ in the porosity of the fibrin clot structure. The dense fibrin network in the t-PA-resistant group may prevent access to plasmin, suggesting a mechanism for thrombotic morbidity after injury.
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