The Role of Exposed Phosphatidylserine on Microparticles and Blood Cells in Coagulant Activity in Acute Kidney Injury Patients on Continuous Renal Replacement Therapy
Authors: Liang Hui , Hou Li , Li Tao , Zhang Yan , LI Baorong , Liu Yingmiao , Zhang Cong , Kou Yan , Zou Lili , Guan Yuqing , Chen Xiaojing , Shi Jialan , Xie Rujuan 
Published: October 2019

Abstract
Introduction: Serving as the preferred treatment for patients with acute kidney injury (AKI), continuous renal replacement therapy (CRRT) is mostly interrupted by clotting caused by procoagulant state despite of persistent improvements in anticoagulant technology, reducing therapy time, enhancing cost and resulting in blood lost. Due to hemodynamics disorders and foreign material circuit, blood cells undergo definite activation. However, considered as markers of cell activation, the role of phosphatidylserine (PS) and microparticles (MPs) in the hypercoagulability remains largely unexplored. The aim of this study is to measure PS exposure on blood cells and MPs at baseline and after different therapy duration in AKI patients.
Methods: Fifty AKI patients admitted to the First Affiliated Hospital of Harbin Medical University between March 2017 and May 2018 and forty healthy controls were enrolled in this study. Plasma samples were collected at baseline from patients were diagnosed with AKI and after receiving CRRT (Mode: CVVH; dose: 25mL/kg/h; Citrate which has relative little influence on PS exposure and MPs count was used as regional anticoagulant.) for 6hours, 12hours, 18hours, as well as from healthy controls. After being isolated, MPs were measured by flow cytometry (FCM) while procoagulant activity (PCA) of erythrocytes, platelets and MPs was assessed through coagulation time and purified coagulation complex. Lactadherin was applied as a probe and inhibitor of PS.
Results: Between AKI baseline group and healthy controls, there was no obvious difference in lactadherin+ MPs, exposure on platelets and erythrocytes (Table 1,2), coagulation time and protein production (Fig. 1). While with therapy time prolonged to 6h, 12h and 18h, lactadherin+ MPs and blood cells showed a significant increase compared with baseline group (Table 1,2). Additionally, coagulation time shortened significantly (Fig. 1A) and purified coagulation complex increased visibly in parallel with total therapy time (Fig. 1B-D). Based on previous analysis, we used lactadherin to suppress PS exposure at time point 18h. Compared with the baseline, lactadherin+ MPs count declined by 75.5% (P < 0.001), coagulation time for MPs, platelets and erythrocytes was shortened by 74.6%, 77.2% and 71.9% (all p < 0.01) and procoagulant enzyme complexes were also reduced by 73.8, 78.7% and 72.9% (all p < 0.01). (Figure. 1)
Conclusions: Our results first reveal that upon AKI patients on CRRT, a procoagulant role of PS-driven PCA and an immediate time-dependent elevation in PS+ MPs and blood cells is observed. What's more, suppression of PS obviously inhibits the PCA. Accordingly, PS shows potential to be a new predictor and new strategies focusing on blockade of PS may provide a novel way of anticoagulants in CRRT process.

Disclosures
No relevant conflicts of interest to declare.