PLoS neglected tropical diseases · 2025
ADAMTS13 in Bothrops lanceolatus snakebite envenoming: Crude venom-induced reduction of in vitro enzymatic activity and clinical correlation in snakebite patients.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Florentin Jonathan, Rapon Caroline, Pierre-Louis Olivier, Radouani Fatima, Jalta Prisca, Fuseau Pascal, Kallel Hatem, Neviere Remi, Resiere Dabor
Аннотация
BACKGROUND: Envenoming by Bothrops lanceolatus, a viperid endemic to Martinique an island in the Lesser Antilles, induces a unique clinical manifestation, i.e., thrombosis. Pathophysiological signaling leading to thrombotic events remains poorly understood. Among others, proposed mechanisms include increased expression of multimerized forms of von Willebrand factor (VWF). Prothrombotic effects of VWF are regulated by ADAMTS13, a metalloprotease which cleaves VWF multimers. Whether ADAMTS13 activity is reduced in B. lanceolatus envenoming has not been previously investigated.
METHODOLOGY/PRINCIPAL FINDINGS: ADAMTS13 activity was evaluated via chromogenic assay in experimental and clinical studies. Human plasma with known ADAMTS13 activities (0.70 IU/mL) was incubated with increasing doses of B. lanceolatus venom. Incubation with B. lanceolatus venom (concentrations 10-1000 ng/mL) induced a dose-dependent reduction of ADAMTS13 activity. In our series of 46 patients bitten by B. lanceolatus snake, ADAMTS13 activity was determined at admission before antivenom therapy. In these patients, the median plasmatic ADAMTS13 activity was 94% (IQR: 78-122%). Ten patients (22%) displayed ADAMTS13 activity less than 75%. Compared with patients with normal ADAMTS13 activity (n = 36), those with moderately low ADAMTS13 activity (n = 10) were older, had a lower platelet count, and displayed increased concentrations of creatine kinase, fibrinogen and C-reactive protein. Multivariate linear regression retained only grade severity of envenoming as independent predictor of increase length of hospital stay, while reduced ADAMTS13 activity and increased C-reactive protein levels bordered on statistical significance.
CONCLUSIONS/SIGNIFICANCE: For the first time, our study provided evidence suggesting that ADAMTS13 activity is reduced in experimental B. lanceolatus venom exposure and patients with B. lanceolatus envenoming. Thanks to its role on the VWF regulation, it is suggested that reduced ADAMTS13 activity can increase the risk of thrombosis in B. lanceolatus envenoming by favoring the circulation of prothrombotic VWF multimers. Low ADAMTS13 activity was associated with increased length of stay in envenomed patients.
METHODOLOGY/PRINCIPAL FINDINGS: ADAMTS13 activity was evaluated via chromogenic assay in experimental and clinical studies. Human plasma with known ADAMTS13 activities (0.70 IU/mL) was incubated with increasing doses of B. lanceolatus venom. Incubation with B. lanceolatus venom (concentrations 10-1000 ng/mL) induced a dose-dependent reduction of ADAMTS13 activity. In our series of 46 patients bitten by B. lanceolatus snake, ADAMTS13 activity was determined at admission before antivenom therapy. In these patients, the median plasmatic ADAMTS13 activity was 94% (IQR: 78-122%). Ten patients (22%) displayed ADAMTS13 activity less than 75%. Compared with patients with normal ADAMTS13 activity (n = 36), those with moderately low ADAMTS13 activity (n = 10) were older, had a lower platelet count, and displayed increased concentrations of creatine kinase, fibrinogen and C-reactive protein. Multivariate linear regression retained only grade severity of envenoming as independent predictor of increase length of hospital stay, while reduced ADAMTS13 activity and increased C-reactive protein levels bordered on statistical significance.
CONCLUSIONS/SIGNIFICANCE: For the first time, our study provided evidence suggesting that ADAMTS13 activity is reduced in experimental B. lanceolatus venom exposure and patients with B. lanceolatus envenoming. Thanks to its role on the VWF regulation, it is suggested that reduced ADAMTS13 activity can increase the risk of thrombosis in B. lanceolatus envenoming by favoring the circulation of prothrombotic VWF multimers. Low ADAMTS13 activity was associated with increased length of stay in envenomed patients.