The evolution of activated protein C plasma levels in septic shock and its association with mortality: A prospective observational study

Becher, Tobias; Müller, Jens; Akın, İbrahim; Baumann, Stefan; Bosch, Katharina; Stach, Ksenija; Borggrefe, Martin; Pötzsch, Bernd; Loßnitzer, Dirk

doi:10.1016/j.jcrc.2018.06.003

Cited by 12 publications

(6 citation statements)

References 31 publications

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“…20 min [ 18 , 26 ]. Based on these characteristics, elevated APC plasma levels on admission were found to be an independent predictor of mortality in patients with septic shock [ 34 ]. In the present study, when compared to other hemostatic biomarkers as done by ROC curve analysis, APC was identified as candidate marker to identify patients at risk for TIC.…”

Section: Discussionmentioning

confidence: 99%

Plasmatic coagulation profile after major traumatic injury: a prospective observational study

Caspers

Schäfer

Bouillon

et al. 2022

Eur J Trauma Emerg Surg

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Purpose Uncontrolled hemorrhage is still the major cause of preventable death after trauma and is aggravated by trauma-induced coagulopathy (TIC). The underlying pathophysiology of TIC is still elusive, but several key effectors such as the thrombin-generation capacity, the protein C (PC) pathway, and the fibrinolytic activity could be identified. The aim of this prospective observational study was to investigate plasma coagulation markers attributed to reflect the course of TIC and to identify the mechanisms being responsible for the coagulopathy after major trauma. Methods Seventy-three consecutive patients after major trauma and admission to a level-1-trauma unit were included to the study. During early trauma management, extended coagulation testing including the measurement of circulating thrombin markers and activated PC (APC) was performed and correlated with standard shock parameters and the patients’ clinical course and outcome. Results In contrast to standard coagulation parameters, thrombin markers and APC were found to be increased in correlation with injury severity. Even in patients with lower impact mechanisms, early endogenous accumulation of thrombin markers and APC (ISS < 16: 0.5 ng/ml; ISS ≥ 16–26: 1.5 ng/ml; ISS > 26: 4.1 ng/ml) were observed. Furthermore, APC showed ISS- and injury-dependent patterns while ROC curve analysis revealed that especially APC plasma levels were predictive for coagulopathy and general patient outcome. Conclusion Increased levels of APC and thrombin markers in patients after major trauma were positively correlated with injury severity. APC showed an ISS- and injury-dependent kinetic and might serve as candidate biomarker to identify patients at risk for developing TIC.

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Section: Discussionmentioning

confidence: 99%

Plasmatic coagulation profile after major traumatic injury: a prospective observational study

Caspers

Schäfer

Bouillon

et al. 2022

Eur J Trauma Emerg Surg

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“…Müller et al initially described the OECA for thrombin measurement [41] and the OECA for APC measurement [42], which were used in various other studies [30][31][32][43][44][45][46][47][48]: In brief, bovine serum albumin-biotin-coated microtiter modules (10 µg/mL, 100 µL/well) incubated overnight at 4°C. After washing, 10 µg/mL streptavidin were added to the wells and incubated at room temperature for one hour.…”

Section: Laboratory Analysismentioning

confidence: 99%

Coagulation activation-induced fibrinolysis biomarker changes depend on thrombophilic risk factors and their clinical phenotype: an interventionalin vivostudy

Reda,

Schwarz,

Müller

et al. 2023

Preprint

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BackgroundRecently we have shown alterations in the anticoagulant response to recombinant activated factor VII (rFVIIa)-induced coagulation activation in patients with thrombophilia.ObjectivesHere we extended thisin vivomodel to study fibrinolysis biomarkers.MethodsThe study population included 56 patients with thrombophilia and a history of venous thromboembolism (VTE+), 38 asymptomatic patients with thrombophilia (VTE-) and 35 healthy controls. Plasma levels of D-dimer, plasmin-α2-antiplasmin complex (PAP), and plasminogen activator inhibitor-1 (PAI-1) were monitored over 8 hours after rFVIIa infusion (15 µg/kg) along with thrombin activation markers and activated protein C (APC).ResultsIn all cohorts, PAP increased (P<3.9·10-10) and PAI-1 decreased (P<3.5·10-8). In contrast to thrombin-antithrombin complex (TAT), which also increased temporarily in all cohorts (P<3.6·10-6), changes of PAP and PAI-1 did not reverse during the observation period. The area under the curve (AUC) of PAP (respectively TAT), as measure of plasmin (respectively thrombin) formation, was greater in the VTE+ cohort than in healthy controls (PAP AUCP=0.003, TAT AUCP=2.5·10-4) and showed correlation (r=0.554). As evidenced by the respective AUCs, asymptomatic factor V Leiden (FVL) carriers in the VTE-cohort showed less PAP formation (P=9·10-4), more pronounced PAI-1 decline (P=0.010), and increased APC formation (P=0.020) than those within the VTE+ group (n=19 each). This was not observed in prothrombin 20210G>A carriers or patients with unexplained familial thrombophilia.ConclusionrFVIIa-induced thrombin formation is associated with fibrinolysis parameter changes outlasting the concomitant anticoagulant response. Both correlate with thrombosis history in FVL and might help to explain its variable clinical expressivity.EssentialsImpairment of fibrinolysis might result in increased risk of thrombosis.We studied fibrinolytic biomarkers after coagulation activation by recombinant factor VIIa.Hereby induced alterations in fibrinolytic biomarkers outlast concomitant anticoagulant changes.Factor V Leiden carriers with or without thrombosis showed distinct fibrinolytic changes.

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“…Концентрация протеина С (APC) увеличивается у пациентов с ишемическим инсультом и септическим шоком и коррелирует с остальными маркерами коагуляции. Повышенные уровни APC при поступлении являются независимым предиктором смертности (Becher et al, 2018). В экспериментальном исследовании показано, что маркеры коагуляции, включая протеин С и D-димеры, положительно коррелируют с возрастом (Rhu et al, 2018).…”

Section: протеин сunclassified

Протеин С, D-Димеры И Микроэлементы При Ишемическом Инсульте: Обзор Литературы

Мазилина¹,

Фесюн²,

Яковлев³

et al. 2021

TEM

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Исследованы молекулярные и субмолекулярные механизмы этиопатогенеза ишемического инсульта. Факторы свертывания крови ‒ протеин С и D-димеры ‒ принимают участие в формировании ишемического очага. Концентрация протеина С у пациентов с ишемическим инсультом увеличивается: активированный протеин C оказывает плейотропное нейрорегенеративное и нейропротекторное действие при инсульте и коррелирует с улучшением функционального статуса. Нейроспецифические белки D-димеры являются маркером активации тромбоцитов: избыток D-димера свидетельствует об активации фибринолиза и связана с воспалением при ишемическом инсульте. Металлолигандный гомеостаз оказывает модулирующее влияние на структуру и функцию белков многокомпонентной системы свертывания крови. Цинк служит эффектором коагуляции, антикоагуляции и фибринолиза и является кофактором антиоксидантных ферментов, защищающих мозг от окислительного стресса. Ионы цинка усиливают связывание активированного протеина C с рецептором протеина C эндотелиальных клеток. Селен входит в состав глутатионовых ферментов, принимающих участие в антиоксидантной защите при сосудистой патологии: селен-содержащие ферменты являются модуляторами функции мозга. Ионы меди модулируют систему свертывания крови, как и антиоксидантную систему. Низкая концентрация магния является фактором риска возникновения инсульта, то есть маркером-предвестником. Как недостаток, так и избыток железа в нервной ткани приводит к усилению прооксидантных процессов. Высокий уровень ферритина в сыворотке крови является фактором риска инсульта. Таким образом, макро- и микроэлементный баланс  основа молекулярных механизмов ишемического инсульта.

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The evolution of activated protein C plasma levels in septic shock and its association with mortality: A prospective observational study

Cited by 12 publications

References 31 publications

Plasmatic coagulation profile after major traumatic injury: a prospective observational study

Plasmatic coagulation profile after major traumatic injury: a prospective observational study

Coagulation activation-induced fibrinolysis biomarker changes depend on thrombophilic risk factors and their clinical phenotype: an interventionalin vivostudy

Протеин С, D-Димеры И Микроэлементы При Ишемическом Инсульте: Обзор Литературы

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