Department of Health Sciences, Thrombosis and Atherosclerosis Research Institute (TaARI), McMaster University, Hamilton, Ontario, Canada.
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
PLoS One. 2021 Feb 19;16(2):e0247017. doi: 10.1371/journal.pone.0247017. eCollection 2021.
Sepsis is a life-threatening disease characterized by excessive host response to infection that can lead to activation of the coagulation system. Von Willebrand Factor (VWF) and ADAMTS13 are important regulators of hemostasis and their dysregulation during sepsis progression is not well understood. Herein we characterize ADAMTS13 and VWF in septic and non-septic patients. ADAMTS13 activity, ADAMTS13 antigen, VWF antigen, myeloperoxidase, and protein C, were measured in plasma collected from 40 septic patients (20 non-survivors and 20 survivors) and 40 non-septic patients on the first and last day of their ICU stay. ADAMTS13 activity and ADAMTS13 antigen were reduced, whereas VWF antigen was elevated among septic patients compared to non-septic patients and healthy controls. Non-septic patients also exhibited elevated VWF antigen and reduced ADAMTS13 activity, but to a lesser extent than septic patients. Non-survivor septic patients exhibited the lowest levels of ADAMTS13 activity. ADAMTS13 activity:antigen ratio was similar across all patient cohorts suggesting that the specific activity of ADAMTS13 remains unchanged. Therefore, reduced ADAMTS13 function in circulation is likely due to a reduction in circulating levels. We suggest that massive release of VWF in response to inflammation consumes limited circulating ADAMTS13, resulting in the imbalance observed between VWF and ADAMTS13 among septic and to a lesser extent in non-septic ICU patients. Changes to ADAMTS13 did not correlate with myeloperoxidase or protein C levels. Reduced ADAMTS13 activity and antigen, and elevated VWF antigen observed among all patient cohorts on admission remained unchanged in survivors at ICU discharge. Prolonged reduction in ADAMTS13 activity and antigen in septic patients coincides with elevated levels of VWF. The persistent abnormalities in ADAMTS13 and VWF in sepsis patients discharged from the ICU may contribute to a sustained prothrombotic state.
脓毒症是一种危及生命的疾病，其特征是宿主对感染的过度反应，可导致凝血系统激活。血管性血友病因子（VWF）和 ADAMTS13 是止血的重要调节剂，但其在脓毒症进展过程中的失调尚不清楚。在此，我们对脓毒症和非脓毒症患者的 ADAMTS13 和 VWF 进行了描述。在入住 ICU 的第一天和最后一天，从 40 名脓毒症患者（20 名非幸存者和 20 名幸存者）和 40 名非脓毒症患者的血浆中测量了 ADAMTS13 活性、ADAMTS13 抗原、VWF 抗原、髓过氧化物酶和蛋白 C。与非脓毒症患者和健康对照者相比，脓毒症患者的 ADAMTS13 活性和 ADAMTS13 抗原降低，而 VWF 抗原升高。非脓毒症患者也表现出 VWF 抗原升高和 ADAMTS13 活性降低，但程度低于脓毒症患者。非幸存者脓毒症患者的 ADAMTS13 活性最低。所有患者队列的 ADAMTS13 活性：抗原比值相似，提示 ADAMTS13 的特异性活性保持不变。因此，循环中 ADAMTS13 功能的降低可能是由于循环水平的降低。我们认为，炎症反应引起的 VWF 大量释放消耗了有限的循环 ADAMTS13，导致脓毒症患者和在较小程度上 ICU 非脓毒症患者中观察到的 VWF 和 ADAMTS13 之间的失衡。ADAMTS13 的变化与髓过氧化物酶或蛋白 C 水平无关。所有患者入院时观察到的 ADAMTS13 活性和抗原降低以及 VWF 抗原升高，在 ICU 出院时的幸存者中保持不变。脓毒症患者 ADAMTS13 活性和抗原的持续降低与 VWF 水平升高同时发生。从 ICU 出院的脓毒症患者中 ADAMTS13 和 VWF 的持续异常可能导致持续的血栓形成状态。
