Early abnormal fibrinolysis and mortality in patients with thermal injury: a prospective cohort study

Abstract

Introduction Abnormal fibrinolysis early after injury has been associated with increased mortality in trauma patients, but no studies have addressed patients with burn injury. This prospective cohort study aimed to characterize fibrinolytic phenotypes in burn patients and to see if they were associated with mortality. Methods Patients presenting to a regional burn centre within 4 h of thermal injury were included. Blood was collected for sequential viscoelastic measurements using thromboelastography (RapidTEG™) over 12 h. The percentage decrease in clot strength 30 min after the time of maximal clot strength (LY30) was used to categorize patients into hypofibrinolytic/fibrinolytic shutdown (SD), physiological (PHYS) and hyperfibrinolytic (HF) phenotypes. Injury characteristics, demographics and outcomes were compared. Results Of 115 included patients, just over two thirds were male. Overall median age was 40 (i.q.r. 28–57) years and median total body surface area (TBSA) burn was 13 (i.q.r. 6–30) per cent. Some 42 (36.5 per cent) patients had severe burns affecting over 20 per cent TBSA. Overall mortality was 18.3 per cent. At admission 60.0 per cent were PHYS, 30.4 per cent were SD and 9.6 per cent HF. HF was associated with increased risk of mortality on admission (odds ratio 12.61 (95 per cent c.i. 1.12 to 142.57); P = 0.041) but not later during the admission when its incidence also decreased. Admission SD was not associated with mortality, but incidence increased and by 4 h and beyond, SD was associated with increased mortality, compared with PHYS (odds ratio 8.27 (95 per cent c.i. 1.16 to 58.95); P = 0.034). Discussion Early abnormal fibrinolytic function is associated with mortality in burn patients.

Inhalation Injury Is Associated With Endotheliopathy and Abnormal Fibrinolytic Phenotypes in Burn Patients: A Cohort Study

“…Previous work suggests that abnormal fibrinolysis is associated with poor outcomes in burn and nonburn trauma. 19,26,[39][40][41][42][43][44][45][46][47] One potential mechanism behind abnormal systemic fibrinolysis caused by IHI is circulating plasminogen activator inhibitor (PAI-1), the main inhibitor of fibrinolysis, that is elevated in bronchoalveolar lavage fluid as well as in the systemic circulation following acute lung injury. [48][49][50] When rTEG parameters were compared between burn patients with and without IHI in the first 24 hours after injury, there was a pattern of significantly lower LY30 measurements among patients with IHI at hours 4 and 12, with a similar trend at hours 8 and 24 (Figure 2D).…”

“…17 Abnormal fibrinolysis is associated with poor outcomes and mortality in burn and nonburn trauma. 18 , 19 Syndecan-1 (SDC-1) is a transmembrane proteoglycan constituent of the vascular endothelium that is shed into the plasma in response to injury. SDC-1 serves as a biomarker for endothelial dysfunction or endotheliopathy.…”

Coagulopathy in Patients with Severe Burn Injury: A Literature Review

“…Так, при травматической коагулопатии наблюдается снижение уровня ФV из-за APC-опосредованного протеолиза [37]. Активность ФVIIa повышена в первые 48 часов после термического повреждения и коррелирует с тяжестью травмы и с прогнозом [40]. ФVIII быстро увеличивается в течение первых 48 часов и остается выше нормальных значений до 40 дней после травмы [38,43].…”

“…Следует проявлять осторожность при попытке определить состояние гипер-или гипокоагуляции, основываясь исключительно на уровнях отдельных маркеров. Исследования демонстрируют индукцию обоих состояний в раннем периоде ожоговой болезни [14,40].…”

“…Цитокины, продуцируемые лейкоцитами в ответ на инфекционные процессы, стимулируют экспрессию ТФ и последующую активацию коагуляции. Так, ИЛ-6 может инициировать экспрессию ТФ в мононуклеарных клетках, а ингибирование этого цитокина может блокировать ТФзависимую генерацию тромбина [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. ФНО-а, цитокин, продуцируемый моноцитами крови и тканевыми макрофагами в условиях эндотоксемии и воспаления, может стимулировать экспрессию ТФ несколькими клеточными линиями, включая эндотелий.…”