Objective To observe the protective effects of unfractionated heparin (UFH) on high-mobility group box-1 protein (HMGB1) induced increased permeability of endothelial cells, and investigate the protective mechanism of UFH on HMGB1 induced defective expression of zonula occludens-1 (ZO-1). Methods Human umbilical vascular endothelial cells (HUVECs) were culturedin vitro and divided into 4 groups (n=5), namely a control group, a HMGB1 group (100 ng/ml), a heparin group (UFH 10 U/ml), a HMGB1/heparin group (100 ng/ml HMGB1 + UFH 10 U/ml). Endothelial cell viability was measured by methyl thiazolyl tetrazolium (MTT) colorimetric method. Endothelial permeability was determination by Transwell chamber method. Immunofluorescence and laser confocal microscopy were used to assess the distribution of ZO-1. The protein expressions of tight junction protein ZO-1 and nuclear factor kappa B (NF-κB) were detected by Western blot. Results HMGB1 (100 ng/ml) had no inhibitory effect on endothelial cell viability (P＞0.05). UFH pretreatment could reduce the permeability increment of endothelial cells induced by HMGB1. UFH pretreatment could reduce the close loop reduction and damage of ZO-1 induced by HMGB1, enhance the fluorescence intensity and expression of ZO-1, and decrease the NF-κB translocation. Conclusions UFH can protect HMGB1-mediated defect of ZO-1 expression and increased permeability of the endothelial cells. The mechanism may be related to the decreased nuclear translocation of NF-κB.
ObjectiveTo evaluate the correlation of activated partial thromboplastin time (aPTT), activated clotting time (ACT) and the activity of anti-factor Ⅹa activity with the concentration of unfractionated heparin (UFH) during extracorporeal membrane oxygenation (ECMO) in children after cardiac surgery.MethodsThe clinical data of children (aged 6 months to 6 years) who received ECMO support after cardiac surgery in Fuwai Hospital from January 2010 to October 2020 were retrospectively collected. And the aPTT value, ACT value, anti-Ⅹa activity and the corresponding UFH dose measured simultaneously during ECMO were recorded. According to the Extracorporeal Life Support Organization anticoagulation guideline, the bleeding events of children during ECMO support were defined, and the children were divided into a bleeding group and a non-bleeding group according to whether bleeding events occurred. Pearson correlation was used to evaluate the correlation between ACT, aPTT or anti-Ⅹa activity and UFH in the same patient.ResultsA total of 58 children, including 33 males and 25 females, aged 27.31±34.17 months, were enrolled and divided into the bleeding group (n=39) and the non-bleeding group (n=19). Univariate analysis showed that compared with children in the non-bleeding group, children in the bleeding group had lower red blood cell counts (P=0.049), hemoglobin concentration (P=0.010), and hematocrit (P=0.046) on the day of ECMO installation. In addition, the transfusion volume of fresh frozen plasma (P=0.034) and fibrinogen (P=0.033) in the bleeding group was relatively more, and the proportion of exploratory thoracotomy for hemostasis was high (P=0.000); there was a moderate degree of correlation between anti-Ⅹa and UFH (r=0.418, P=0.013) but there was no correlation between ACT or aPTT and UFH.ConclusionThe aPTT value and ACT value are poorly correlated with the concentration of UFH transfused during ECMO in children after cardiac surgery, while the anti-Ⅹa activity is moderately correlated with it.
ObjectiveTo evaluate the economics of nafamostat mesylate compared with unfractionated heparin for continuous renal replacement therapy anticoagulation. MethodsA decision tree model was constructed to calculate the cost difference between the two anticoagulation methods. Survival analysis data comes from retrospective literature in Asian countries. The cost data comes from procurement data and the prices of medical and health services in some regions. A 72-hour scenario analysis is performed and a sensitivity analysis is performed on key parameters. ResultsThe basic analysis results showed that compared with the unfractionated heparin group, the total cost difference of nafamostat in the 144-hour CRRT treatment was 5 350.34 yuan, and the unfractionated heparin was more economical. In the 72-hour scenario analysis, unfractionated heparin is also more economical. Univariate sensitivity analysis showed that the cost of single-use hemodialysis filters and supporting pipelines and the cost of plasma antithrombin Ⅲ activity (AT-Ⅲ) measurement had a greater impact on the change of the cost difference. The results of probability sensitivity analysis show that the model structure is stable and robust. When the unit price of nafamostat is about 110.82 yuan/piece, the cost of nafamostat and unfractionated heparin in 144-hour CRRT treatment is both 19 185.37 yuan, and the cost difference is 0.ConclusionWhen the unit price of nafamostat mesylate drops to a sufficiently low level, it could have an advantageous health economy.