177 Novel antifibrinolytic therapy to target Acute Traumatic Coagulopathy (ATC) during major traumatic haemorrhage
Year: 2025
Type: article
Abstract: Background ATC can cause hyperfibrinolysis and fibrinogen loss through activated Protein C (aPC) consuming Plasminogen Activator Inhibitor (PAI)-1. Attempts at using blood transfusions, Tranexamic Acid, and utilising a point-of-care viscoelastic assessment have also proven ineffective. Most patients remain coagulopathic, associated with a high mortality. A recombinant (r)PAI-1 has been engineered with a significantly longer half-life. Aims 1. Characterise the temporal changes of PAI-1 in bleeding patients; 2. Determine the efficacy of rPAI-1 in a murine ATC model. Methods Bleeding trauma patients were included with blood samples collected on admission and after transfusion of 4, 8 and 12 units of blood for PAI-1 and aPC. In a preclinical model of ATC, two groups were treated with vehicle (saline) or rPAI-1 thirty minutes after haemorrhage. Terminal blood was analysed for biomarkers of coagulation, fibrinolysis and nanoscopic clot architecture. Results 31 trauma patients were included. Admission PAI-1 was similar between the two groups. However, patients with an ongoing generation of aPC had a 58% mortality rate and a PAI-1 of 59ng/ml by 12 units of blood. Patients with a lowering aPC had a median PAI-1 of 95ng/ml by 12 units and zero deaths. Compared to vehicle, mice infused with rPAI-1 had significantly higher survival with a hazard ratio of 3.10 (95% CI 0.93 – 10.34). Biomarkers indicated improvement in fibrinolysis, fibrinogenolysis, and coagulopathy. Clot architecture was appreciably improved. Conclusion PAI-1 in bleeding trauma patients decreases and is not corrected by current standard therapy. rPAI-1 replacement may represent a novel therapy for ATC.
Source: British journal of surgery
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4408369246