Antithrombin III Levels Research Articles

Antithrombin III infusion improves anticoagulation in congenital diaphragmatic hernia patients on extracorporeal membrane oxygenation.

Achieving effective anticoagulation during neonatal extracorporeal membrane oxygenation (ECMO) without increasing the risk of hemorrhage remains challenging. The use of antithrombin III (AT-III) for this purpose has been examined, but studies have been limited to intermittent bolus dosing. We aimed to evaluate the efficacy and safety of an institutionally developed AT-III continuous infusion protocol in neonates receiving ECMO for the treatment of congenital diaphragmatic hernia (CDH). In this single center, retrospective study, all neonates with a CDH who received ECMO support during the study period were included. Data on anticoagulation labs and therapy, life-threatening bleeding, and circuit changes were analyzed. Eleven patients were divided into two groups: patients with AT-III continuous infusion (n = 5) and without (n = 6). There were no differences in the gestational age (p = 0.29), sex (p = 1.00), ECMO duration (p = 0.59), or initial AT-III levels (p = 0.76) between groups. Patients in the AT-III infusion group had on average 18.5% higher AT-III levels (p < 0.0001). Patients receiving continuous AT-III infusions spent a significantly higher percentage of ECMO time within the therapeutic range, measured using anti-Factor Xa levels (64.9±4.2% vs. 29.1±8.57%, p = 0.008), and required fewer changes to the heparin infusion rate (6.48±0.88 vs 2.38±0.36 changes/day changes/day, p = 0.005). Multivariate analysis revealed continuous infusion of AT-III did not increase the rate of intracranial or surgical bleeding (p = 0.27). AT-III as a continuous infusion in CDH neonates on ECMO provides a decreased need to modify heparin infusion and more consistent therapeutic anticoagulation without increasing the risk of life-threatening bleeding.

Effect of microwave ablation on platelet and coagulation function in patients with BCLC-A hepatocellular carcinoma

To preliminarily evaluate the effect of microwave ablation (MWA) alone on platelet (PLT) and coagulation function in patients with BCLC-A hepatocellular carcinoma (B-A-HCC) using a retrospective method. A total of 36 patients with 48 B-A-HCCs were radically treated with MWA alone under the guidance of ultrasound between April and October 2018. PLT coagulation indexes were measured before and after MWA at 1 day, 3 days, 1 week, and 2 weeks, and blood samples (after morning fasting) were collected from cubital veins. Coagulation indexes included prothrombin time (PT), prothrombin activity (PTA), thrombin time (TT), Activated Partial Thromboplastin Time (APTT), international standardized ratio (INR), plasma fibrinogen (FIB), plasma antithrombin III (AT-III), and D dimer (DD). Overall survival (OS), recurrence-free survival (RFS), local tumor progression (LTP), and adverse reactions were also recorded. All patients were radically treated with MWA alone. The median size of the lesion was 2.6 (1.5-7.0) cm3. On the first day after MWA, the level of PLT decreased significantly compared with the values before MWA and gradually returned to preoperative levels one week after MWA. One day after MWA, the levels of PT, INR, and AT-III increased markedly and the level of PTA decreased significantly, all of them gradually returned to baseline after 3 days to a week of time. 1, 3, and 7 days after MWA, the levels of FIB, and DD increased significantly, and the level of TT decreased significantly; all of them gradually returned to baseline at 2 weeks. At 6 months posttreatment, the OS and RFS rates were 100% and 91.7%, the LTP rates was 5.6%, no significant adverse reactions. PLT and coagulation indexes were abnormal in patients with B-A-HCC who were radically treated with MWA alone after treatment; without specific treatment, they all gradually returned to baseline within a week or two.

Adequate Antithrombin III Level Predicts Survival in Severe COVID-19 Pneumonia.

Critically ill patients with COVID-19 are at an increased thrombotic risk, hence thromboprophylaxis with heparin is considered mandatory. Antithrombin III (ATIII) is the most potent endogenous anticoagulant and is required for the clinical efficacy of heparin. Profound hypercoagulable and inflammatory state associated with COVID-19 can result in decreased ATIII levels and ineffective heparin treatment resulting in increased mortality. The present study evaluated ATIII levels in critically ill patients of COVID-19 and correlated them with other coagulation parameters and disease outcomes. A retrospective review of those critically ill COVID-19 patients was performed who were on a therapeutic dose of low molecular weight heparin (LMWH) and had serial measurements of ATIII, anti-factor Xa (antiFXa) assay and other routine coagulation parameters. A total of 27 critically ill COVID-19 patients were identified, out of these, 12 survived and 15 had disease-induced mortality. ATIII levels were found to be significantly lower in non-survivors on the third day of serial measurement along with worsening of other coagulation parameters. AntiFXa levels were found to be higher in non-survivors as compared to survivors. Further studies are required to establish ATIII as a prognostic marker and to determine the utility of monitoring antiFXa levels in COVID-19 patients on LMWH therapy.

Low Preoperative Antithrombin III Level Is Associated with Postoperative Acute Kidney Injury after Liver Transplantation

We aimed to determine the association between the preoperative antithrombin III (ATIII) level and postoperative acute kidney injury (AKI) after LT (post-LT AKI). We retrospectively evaluated 2395 LT recipients between 2010 and 2018 whose data of perioperative ATIII levels were available. Patients were divided into two groups based on the preoperative level of ATIII (ATIII < 50% vs. ATIII ≥ 50%). Multivariable regression analysis was performed to assess the risk factors for post-LT AKI. The mean preoperative ATIII levels were 30.2 ± 11.8% in the ATIII < 50% group and 67.2 ± 13.2% in the ATIII ≥ 50% group. The incidence of post-LT AKI was significantly lower in the ATIII ≥ 50% group compared to that in the ATIII < 50% group (54.7% vs. 75.5%, p < 0.001); odds ratio (OR, per 10% increase in ATIII level) 0.86, 95% confidence interval (CI) 0.81–0.92; p < 0.001. After a backward stepwise regression model, female sex, high body mass index, low albumin, deceased donor LT, longer duration of surgery, and high red blood cell transfusion remained significantly associated with post-LT AKI. A low preoperative ATIII level is associated with post-LT AKI, suggesting that preoperative ATIII might be a prognostic factor for predicting post-LT AKI.

The correlation between coagulation function and prognosis in patients with acute respiratory distress syndrome caused by extrapulmonary sepsis or pulmonary infection

Objective: To explore the difference of coagulation function and its correlation with prognosis in patients with acute respiratory distress syndrome (ARDS) caused by extrapulmonary sepsis and pulmonary infection. Methods: ARDS patients caused by extrapulmonary sepsis and pulmonary infection admitted to the ICU were retrospectively analyzed at the First Affiliated Hospital of China Medical University from July 2017 to June 2019. The clinical characteristics were collected including sequential organ failure assessment (SOFA), coagulation parameters [prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fib), D-Dimer (D-D), fibrinogen degradation product (FDP), antithrombin Ⅲ(AT-Ⅲ), platelet (PLT)], duration of mechanical ventilation, length of stay (LOS) in ICU and 28-day mortality. According to the risk factors, the patients were divided into extrapulmonary sepsis group and pulmonary infection group. The correlation analysis between coagulation parameters and the prognosis of ARDS patients were analyzed by multivariate logistic regression analysis. Results: A total of 268 ARDS patients were screened and 28 cases were excluded. Finally, 240 ARDS patients were enrolled, including 145 caused by extrapulmonary sepsis and 95 by pulmonary infection. PT, INR and APTT in the extrapulmonary sepsis group were significantly higher than those in pulmonary infection group (P<0.05). AT-Ⅲ level was lower than that in pulmonary infection group (P<0.05). Ninty-three patients survived at 28 days in the non-pulmonary sepsis group, the mortality rate was 35.9% (52/145). PT, INR, APTT in patients who died at 28 days were significantly higher than those of the patients who survived (P<0.05), while AT-Ⅲ level was lower than those of the patients who survived (P<0.05). 49 patients survived at 28 days in the pulmonary infection group, the mortality rate was 48.4% (46/95). There was no significant difference in the coagulation parameters between two groups. Multivariate logistic regression analysis showed that SOFA score without PLT(OR=1.210,95%CI 1.067-1.372,P=0.003) and INR (OR=2.408,95%CI 1.007-5.760,P=0.048) were independent risk factors for 28-day mortality in extrapulmonary sepsis group. Coagulation parameters are not independent risk factors for 28-day mortality in ARDS patients related to pulmonary infection. Conclusion: There are significant differences in coagulation function between ARDS patients caused by extrapulmonary sepsis or pulmonary infection. INR is an independent risk factor for 28-day mortality in extrapulmonary sepsis group.

Venous thromboembolism incidence and risk factors in adults with acute lymphoblastic leukemia treated with and without pegylated E. coli asparaginase-containing regimens.

Asparaginases, key agents in treatment of acute lymphoblastic leukemia (ALL), are associated with venous thromboembolism (VTE). While risks of short-acting asparaginase-related VTE is well-known, we studied VTE incidence and risk factors in adult ALL patients treated with and without long-acting pegylated asparaginase (PegA). Single-center, retrospective analysis of 89 ALL patients treated with (n = 61) or without (n = 28) PegA at Greenebaum Comprehensive Cancer Center. Reviewed patient and disease characteristics, treatment, and VTE incidence. VTE during treatment occurred in 31 patients (35%), and was associated with PegA (p = 0.001) and Philadelphia chromosome negativity (p = 0.002). Among PegA recipients, VTE was associated with a significantly higher mean body mass index (BMI) of 31.3kg/m2 (p = 0.037), and was more common with pre-T/T cell compared to pre-B/B cell ALL (68.2% vs. 33.3%, p = 0.009). Antithrombin-III (ATIII) levels were measured for 26 patients; 16 (61.5%) were < 50%. Of those, 8 (50%) experienced VTE, while 3 of 10 (30%) patients with ATIII levels ≥ 50% experienced VTE. VTE occurred in 7 of 13 (54%) of patients who received ATIII repletion. There was a trend toward a higher incidence of VTE in the PegA group among patients with non-O compared to O blood type (55.9% vs. 33.3%, p = 0.079) as well as those with a higher hemoglobin at diagnosis (9.3 vs 8.1g/dL, p = 0.056). This study confirms PegA as a risk factor for VTE in patients with ALL. Risk factors among those receiving PegA include higher BMI and pre-T/T cell ALL. ATIII repletion was not shown to be protective against VTE. There was a higher incidence of VTE in patients who received PegA with non-O compared to O blood type, but the precise correlation is uncertain.

Low level of postoperative plasma antithrombin III is associated with portal vein thrombosis after liver surgery.

Although decreased antithrombin-III (AT-III) is a risk factor for portal vein thrombosis (PVT) in patients with liver cirrhosis, the association between postoperative PVT and postoperative AT-III levels is unknown in patients undergoing hepatectomy. Patients who underwent hepatectomy between 2015 and 2018 were retrospectively analyzed. Postoperative PVT was assessed on CT at days 6-9 after hepatectomy. One-to-one propensity score (PS) matching was used to match the baseline characteristics. Of the 295 patients included in this analysis, 19 patients (6.4%) were diagnosed with postoperative PVT. The AT-III level on postoperative day (POD) 3 predicted postoperative PVT with a sensitivity/specificity of 74%/59% (AUC, 0.644; cut-off value, 60%; p = 0.032). Multivariate analysis revealed that AT-III levels ≤ 60% on POD3 (OR, 3.01; 95% CI 1.02-8.89; p = 0.046), cirrhosis (OR, 5.88; 95% CI 1.92-18.0; p = 0.002) and right-sided hepatectomy (OR, 4.16; 95% CI 1.45-11.9; p = 0.0079) were significant risk factors for postoperative PVT. After PS matching, 56 patients with and without AT-III supplementation were analyzed. The two groups had a similar incidence of PVT (p = 0.489). Patients with AT-III levels ≤ 60% on POD3 should be carefully followed up regarding postoperative PVT. Our results did not support the efficacy of routine AT-III supplementation for the prophylaxis of postoperative PVT.

Effects of andrographolide on the expression of procoagulant and fibrinolytic inhibition factors in rat type II alveolar epithelial cells stimulated by lipopolysaccharide

To determine the effect of andrographolide (AD) on the expression of procoagulant and fibrinolytic inhibitory factors in rat type II alveolar epithelial cells (AEC II) stimulated by lipopolysaccharide (LPS). The AEC II cells RLE-6TN in the logarithmic growth phase were divided into 5 groups: the normal control (NC) group, the LPS group, and the 6.25, 12.5, and 25 mg/L AD groups (AD 6.25 group, AD 12.5 group, AD 25 group). The NC group was cultured with RPMI 1640 conventional medium. In the LPS group, 5 mg/L LPS was added to the RPMI 1640 conventional medium for stimulation. Cells in the AD groups were treated with 6.25, 12.5, and 25 mg/L AD in advance for 1 hour and then given LPS to stimulate the culture. The cells and cell culture supernatant were collected 24 hours after LPS stimulation. The protein and mRNA expressions of tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibition-1 (PAI-1) in cells were detected by Western blotting and real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). The levels of procollagen III peptide (PIIIP), thrombin-antithrombin complex (TAT), antithrombin III (AT-III) and activated protein C (APC) in the cell supernatant were detected by enzyme linked immunosorbent assay (ELISA). Compared with the NC group, the protein and mRNA expressions of TF and PAI-1 in the LPS group were significantly increased, and the protein and mRNA expressions of TFPI were significantly reduced. At the same time, the levels of PIIIP and TAT in the cell supernatant were significantly increased, the levels of AT-III, APC were significantly reduced. Compared with the LPS group, the protein and mRNA expressions of TF and PAI-1 in AD 6.25 group, AD 12.5 group, AD 25 group were significantly reduced [TF/GAPDH: 0.86±0.08, 0.45±0.04, 0.44±0.04 vs. 1.32±0.10, TF mRNA (2-ΔΔCt): 2.59±0.25, 2.27±0.05, 1.95±0.04 vs. 4.60±0.26, PAI-1/GAPDH: 2.11±0.07, 1.45±0.04, 0.86±0.09 vs. 2.56±0.09, PAI-1 mRNA (2-ΔΔCt): 3.50±0.22, 2.23±0.29, 1.84±0.09 vs. 6.60±0.27, all P < 0.05], while the protein and mRNA expressions of TFPI were significantly increased [TFPI/GAPDH: 0.78±0.05, 0.81±0.03, 0.84±0.07 vs. 0.36±0.02, TFPI mRNA (2-ΔΔCt): 0.46±0.09, 0.69±0.07, 0.91±0.08 vs. 0.44±0.06, all P < 0.05]. Also the levels of PIIIP and TAT in the cell supernatant were significantly reduced, and the levels of AT-III and APC were significantly increased [PIIIP (μg/L): 13.59±0.23, 12.66±0.23, 10.59±0.30 vs. 15.82±0.29, TAT (ng/L): 211.57±6.41, 205.69±4.04, 200.56±9.85 vs. 288.67±9.84, AT-III (μg/L): 102.95±3.86, 123.92±2.63, 128.67±1.67 vs. 92.93±3.36, APC (μg/L): 1 188.95±14.99, 1 366.12±39.93, 1 451.15±29.69 vs. 1 145.55±21.07, all P < 0.05]. With the increase of the dose of AD, the above-mentioned promotion and inhibition effects became more obvious. In the AD 25 group, TF, PAI-1 protein and mRNA expressions decreased, TFPI mRNA expression increased, PIIIP level in the supernatant decreased and AT-III, APC levels increased compared with AD 6.25 group, the difference was statistically significant, and the decrease of PAI-1 protein expression and PIIIP level in the supernatant were also statistically significant compared with AD 12.5 group. Andrographolide in the dose range of 6.25-25 mg/L can dose-dependently inhibit the expression and secretion of procoagulant and fibrinolytic inhibitor-related factors in AEC II cells RLE-6TN stimulated by LPS, and promote the secretion of anticoagulant factors. 25 mg/L has the most obvious effect.

Low Level of Postoperative Plasma Antithrombin III Is Associated with Portal Vein Thrombosis after Liver Surgery

Background: Decreased antithrombin-III (AT-III) is a risk factor of portal vein thrombosis (PVT) in patients with liver cirrhosis. The association between PVT and postoperative AT-III is controversial in patients who underwent liver surgery. The efficacy of postoperative AT-III supplementation on PVT is also uncertain. Methods: Patients who underwent hepatectomy for hepato-biliary disease between 2015-2018 were retrospectively analyzed. Donors and recipients for liver transplantation were excluded. Postoperative PVT was assessed on computed tomography on the day 6-9 after hepatectomy. Results: Of the 325 patients included in this analysis, 19 patients (5.8%) were diagnosed as postoperative PVT. AT-III level on postoperative day (POD) 3 predicted postoperative PVT with a sensitivity/specificity of 74%/59% (area under the curve, 0.644; cut-off value, 60%; p=0.032). Univariate analysis revealed that AT-III level ≤60% on POD3 was the only significant risk factor for postoperative PVT (Table). Postoperative AT-III supplementation was not associated with reduced incidence of PVT. Although postoperative AT-III supplementation and major hepatectomy were the significant risk factors for postoperative hemorrhagic complications in univariate analysis, multivariate analysis revealed that major hepatectomy was the only significant risk factor for hemorrhagic complications. Conclusion: Patients with AT-III level ≤60% on POD3 should be given careful attention to postoperative PVT. Although postoperative supplementation of AT-III is safe without increased risk of hemorrhagic complication, the efficacy of it on PVT is still controversial.

Clinical Significance of Serum Antithrombin III Activity After Hepatectomy for Hepatocellular Carcinoma.

As antithrombin III (AT-III) is produced in the hepatocytes, its serum activity decreases at the time of liver failure, in addition to ischemia reperfusion injury, vascular endothelial dysfunction, and disseminated intravascular coagulation (DIC). Here, we examined whether the serum AT-III value after hepatectomy could be a prognostic factor for hepatocellular carcinoma (HCC). Of 141 patients who underwent hepatectomy for HCC, data for 101 patients in whom serum AT-III activity was measured on the first postoperative day were extracted. Patients with serum AT-III activity > 50% and ≤ 50% were assigned to high value (72 cases) and low value (29 cases) groups, respectively. We examined the clinical and prognostic differences between these two groups. The average age of enrolled patients (83 men and 18 women) was 68.0 years. The 5-year overall survival rate was 88% and 60% in the high and low value groups, respectively (P < 0.01). Furthermore, the 2-year relapse-free survival rate was 71% and 54% in the high and low value groups, respectively (P = 0.03). This is the first study to demonstrate that serum AT-III levels on the first postoperative day may serve as a prognostic factor in HCC patients.

Dynamic changes of coagulation and fibrinolytic biomarkers in peri operaive arthroplasty patients.

To evaluate coagulation and fibrinolytic parameters after total joint arthroplasty (TJA) and provide evidence for optimization of timing of perioperative anticoagulation medicine. The prospective study was conducted at the Jishuitan Hospital of Peking University from January to April in 2016, and comprised patients who were scheduled consecutively to undergo primary total knee arthroplasty (TKA) or total hip arthroplasty (THA). Blood samples were obtained at day 1 preoperatively and day1, day 3 postoperatively. Antigenic levels of protein C (PC), endothelial protein C receptor (EPCR), tissue factor pathway inhibitor (TFPI), antithrombin III (AT-III), plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (tPA) were measured with commercially available enzyme-linked immunosorbent assay kits. Postoperative levels of coagulation parameters TFPI and AT-III were increased compared to preoperative values (118.7±34.6 vs 70.0±20.5 μg/ml for AT-III, and 26.37±7.91vs 16.68±8.92 μg/l for TFPI), while postoperative levels of coagulation parameters PC and EPCR were decreased (0.88±0.30 vs 2.03±0.66 μg/ml for PC, and 100.8±31.0 vs 199.4±57.4 μg/ml for EPCR). Postoperative levels of fibrinolytic parameter tPA was increased compared to preoperative values (2.87±0.83 vs 2.03±1.03 μg/l), while its specific inhibitor PAI-1 was decreased (0.88±0.30 vs 2.03±0.66 μg/l). These results demonstrated the perturbation of the coagulation and fibrinolytic system of patients undergoing TJA. Hypercoagulation and hyperfibrinolysis were observed in postoperative patients, which suggested anticoagulant therapy is effective and necessary.

Predictive value of combining the level of fibrinogen and antithrombin III for contrast-induced nephropathy in coronary artery disease patients undergoing percutaneous coronary intervention.

Contrast-induced nephropathy (CIN) is a common adverse event in the diagnosis and treatment of coronary intervention. The current study investigated the predictive effect of preoperative fibrinogen (FIB) combined with antithrombin III (AT-III) on CIN following percutaneous coronary intervention (PCI). A total of 394 patients who underwent PCI between October 2018 and May 2019 were selected for the present study. Pre-procedural FIB levels and AT-III activity were measured before PCI. CIN was defined as a 0.5 mg/dl or 25% increase in serum creatinine levels 48 to 72 h after exposure to a radiocontrast agent. Patients were classified into CIN and non-CIN groups. CIN occurred in 48 (12.2%) patients. The serum FIB levels were significantly higher in patients who developed CIN compared with those who did not develop CIN. In addition, AT-III levels ≤89.5% were associated with higher rates of CIN. Logistical regression analysis showed that high FIB, and low AT-III and albumin levels were high-risk factors associated with CIN. For FIB, the area under the receiver operating characteristic curve (AUC) for predicting CIN was 0.653. The optimal cut-off value was 3.48 g/l with a sensitivity of 45.8% and a specificity of 79.7% [95% confidence interval (CI): 0.603-0.701; P=0.0002)]. For AT-III, the AUC was 0.711, and the optimal cut-off value was 89.5%, with a sensitivity of 81.3% and specificity of 58.2% (95% CI: 0.659-0.758; P<0.0001). When combining FIB and AT-III, the AUC was 0.747. The optimal cut-off value was 0.090424, with a diagnostic sensitivity of 93.8% and specificity of 46.6% (95% CI: 0.697-0.792; P<0.0001). The results showed that FIB combined with AT-III resulted in improved predictive accuracy of CIN (FIB vs. AT-III, AUC=0.653 vs. 0.711, P=0.292; FIB vs. FIB + AT-III, AUC=0.653 vs. 0.747, P=0.012; AT-III vs. FIB + AT-III, AUC=0.711 vs. 0.747, P=0.138). Pre-procedural levels of FIB, AT-III and albumin were independently associated with an increased risk of CIN. Furthermore, the results suggested that the combination of FIB and AT-III was a better predictor of CIN after PCI.

Hemostatic parameters in patients with spinal cord injury in subacute and chronic phase of the rehabilitation

Objective: The goal of this study was to measure hemostatic markers after SCI. Design: Assesing changes in coagulation and fibrynilitic system in SCI patients in different time post injury to Cross-sectional study. Setting: Rehabilitation Department of the Bydgoszcz University Hospital, Poland from 2011 to 2017. Participants: SCI patient during acute and chronic rehabilitation (N = 88). Outcome Measures: Assesing following parameters: platelet counts and levels of D-dimer, antithrombin III (ATIII), tissue factor (TF), tissue factor pathway inhibitor (TFPI) and the inflammatory marker, C-reactive protein (CRP). Interventions: Eighty-eight SCI patients were divided into three groups based on the time elapsed from injury: group I (three weeks to three months), group II (three to twelve months) and group III (more than twelve months). All patients underwent ultrasonography (US) to detect acute or chronic recanalized deep vein thrombosis (DVT). Platelet counts and levels of D-dimer, ATIII, TF, TFPI and CRP were assessed. TF and TFPI levels were measured in the control group of forty healthy individuals without SCI, the rest of the parameters were compared to laboratory norms. Results: D-dimer levels were significantly higher in group I compared to group II (P = .0002) and group III (P < .001). Group II had higher D-dimer levels than group III (P = .032). TFPI levels were higher in group II compared with group III (P = .0041) and control group (P = .000033). TF was significantly higher in all the SCI groups compared with the control group (P < .001). Conclusions: D-dimer and TF levels were still elevated twelve months after SCI. TF levels were also elevated over 12 months after inury. The results may indicate that sub-acute and even chronic SCI patients have disturbed coagulation and fibrynolitic system.

Endothelial protective effect of simvastatin on coagulation system in septic rats

Objective: To investigate the endothelial protective effects of simvastatin on the coagulation system in septic rats. Methods: A total of 54 SD male rats were divided into 3 groups. Six healthy rats were intraperitoneally injected with normal salineas control group. Twenty-four rats in septic group were intraperitoneally injected with normal saline followed by lipopolysaccharide 2.5 mg. Study group had 24 rats intraperitoneally injected with simvastatin followed by lipopolysaccharide. Plasma von Willebrand factor (vWF), thrombomodulin (TM), platelet activating factor (PAF) and antithrombin-Ⅲ (AT-Ⅲ) were tested at 1 h, 3 h, 6 h and 12 h after treatment. Scanning electron microscopy and transmission electron microscopy were used to observe the morphology and apoptosis of rat aorta endothelial cells. Results: Compared with healthy control group, vWF [(68.3±4.8) ng/ml, (59.2±5.1) ng/ml, (74.2±20.1) ng/ml, (53.5±4.0)ng/ml, respectively], TM [(1.4±0.3) ng/ml, (1.6±0.4) ng/ml, (2.8±0.9) ng/ml, (1.4±0.5) ng/ml, respectively], PAF [(29.1±6.5) pg/ml, (28.6±1.5) pg/ml, (28.7±2.7) pg/ml, (18.2±4.1) pg/ml, respectively] and AT-Ⅲ [(262.2±38.1)μg/ml, (233.0±70.4) μg/ml, (218.7±54.7) μg/ml, (162.2±37.2) μg/ml, respectively] were significantly increased in the sepsis group at 1 h, 3 h, 6 h and 12 h (P<0.05). Compared with the sepsis group, the plasma levels of PAF in simvastatin intervention group at 1 h [(15.6±2.5) pg/ml, 3 h(10.4±5.3) pg/ml, 6 h (9.3±1.4) pg/ml, 12 h(11.0±2.7) pg/ml] were significantly decreased, so were the TM level at 6 h (1.6±0.9) ng/ml, and the AT-Ⅲ levels at 1 h[(190.3±29.2) μg/ml],6 h [(104.4±33.6) μg/ml] and 12 h [(73.6±39.0) μg/ml, P<0.05]. Conclusion: In the condition of sepsis, toxins and over-activated inflammatory factors damage the vascular endothelium. A large amount of circulating vWF, TM, PAF, and AT-Ⅲ cause early hypercoagulability. Simvastatin significantly reduces plasma amount of these procoagulants, suggesting it smodification of coagulopathy and vascular protective effectsin a septic rat model.

Antithrombin III expression predicts acute kidney injury in elderly patients with sepsis.

Elderly people represent the age group most frequently affected by acute kidney injury (AKI). The potential of Antithrombin III (ATIII) level for predicting AKI among elderly patients with sepsis is yet to be elucidated. Therefore, the purpose of the present study was to evaluate the ability of ATIII to predict AKI nondevelopment and prognosis in elderly patients with sepsis, in an intensive care unit (ICU). The present study was retrospective and included 107 elderly patients with sepsis who had been admitted to ICUs between October 2015 and March 2018. An assessment of renal function was performed daily by measuring serum creatinine (Cr) level and urine output, and ATIII level was obtained within 48 h of sepsis diagnosis. Among all enrolled patients, 29 (27.1%) developed AKI. ATIII expression was a predictor of AKI nondevelopment [Area under the curve (AUC)-Receiving operator characteristic (ROC)=0.729; sensitivity, 0.700; specificity, 0.714], and the ATIII/Creatine ratio was also a predictor of AKI nondevelopment (AUC-ROC=0.971; sensitivity, 0.900; specificity, 1). The accuracy of ATIII (AUC-ROC=0.681; sensitivity, 0.802; specificity, 0.542) and ATIII/Cr (AUC-ROC=0.804; sensitivity, 0.596; specificity, 0.875) in predicting survival was intermediate. However, the ATIII serum level was able to accurately predict AKI nondevelopment in elderly patients with sepsis, who were admitted to ICUs. Patients were divided into low- and high-ATIII groups using either 66.95% or 55.7% as cut-off values, both of which were used for further analysis. By comparison, the ICU stay was significantly lower in the high-ATIII group [P=0.020 (69.95%) and 0.049 (55.7%)] and off mechanical ventilation time, off continuous renal replacement therapy time and survival time were significantly higher in the high ATIII group [P=0.049, 0.048, and 0.014, respectively (66.95%); and P=0.041, 0.036, and 0.021, respectively (55.7%)]. The current study indicated that ATIII serum level predicts AKI in elderly patients with sepsis, and that low ATIII levels predicted a poorer prognosis.

Both UFH and NAH alleviate shedding of endothelial glycocalyx and coagulopathy in LPS-induced sepsis.

Sepsis commonly progresses to disseminated intravascular coagulation and induces the activation of heparanase (HPA) and the shedding of endothelial glycocalyx constituents, including syndecan-1 (SDC-1) and heparan sulphate (HS). However, the degradation of glycocalyx and its association with coagulation disorders remains undetermined. The present study aimed to evaluate the effect of unfractionated heparin (UFH) and N-acetylheparin (NAH), which is a non-anticoagulant heparin derivative, on endothelial glycocalyx and coagulation function in a lipopolysaccharide (LPS)-induced sepsis rat model, and to compare the differences observed in coagulation function between UFH and NAH. Experimental rats were randomly assigned to four groups: Control; LPS; UFH + LPS; and NAH + LPS. Rats were administered UFH or NAH and subsequently, ~1 min later, administered LPS (10 mg/kg; intravenous). The blood and lung tissues of rats were collected 0.5, 2 and 6 h after LPS injection, and were used for subsequent analysis. The results demonstrated that HPA activity and SDC-1 and HS levels increased, and this increase was associated with inflammatory cytokines and coagulation/fibrinolysis markers in the sepsis rat model. Histopathological examination was performed, and the lung injury score and lung wet/dry ratio indicated that UFH and NAH also significantly improved lung tissue injury. The results of the ELISA analysis demonstrated that UFH and NAH treatment: i) significantly decreased the levels of inflammatory cytokines including tumor necrosis factor-α and interleukin-6; ii) inhibited HPA activity and protected the integrity of the glycocalyx, which was identified by decreased HS and SDC-1 levels; and iii) decreased the levels of prothrombin fragment 1+2, thrombin-antithrombin complex, and plasminogen activator inhibitor-1 and increased the levels of fibrinogen and antithrombin-III. Preconditioning with UFH decreased the plasma activated partial thromboplastin time. These results indicated that UFH and NAH may alleviate sepsis-induced coagulopathy, and this effect may have been due to an inhibition of HPA activity and decrease in the shedding of the endothelial glycocalyx.

Danaparoid sodium-based anticoagulation therapy for portal vein thrombosis in cirrhosis patients

BackgroundPortal vein thrombosis (PVT) is a common complication of cirrhosis. However, in patients with PVT and cirrhosis, there is no clear evidence supporting effective treatment modalities. In this study, we examined the effectiveness and safety of anticoagulation therapy using danaparoid sodium for PVT in patients with cirrhosis.MethodsThis retrospective study assessed 52 cirrhotic patients with PVT treated with danaparoid sodium for 2 weeks between November 2008 and September 2018. The primary outcome measure was the post-treatment status of PVT assessed by reduction in thrombus volume and safety of the therapeutic intervention. PVT status was evaluated with contrast-enhanced computed tomography (CECT). All patients received 1250 units of danaparoid sodium twice daily by intravenous injection for 14 days. Patients on antithrombin III (AT-III) combination therapy were additionally administered 1500 units of AT-III on days 1–5 and days 8–12. Effectiveness was evaluated by CECT from between days 13 and 18. The secondary outcome measure was the prognosis of PVT.ResultsAll patients showed reduction in PVT volume without complications. Return of plasma AT-III level to > 70% during the treatment period contributes to ≥75% reduction of PVT volume. The prognosis in PVT patients depends on hepatic reserve capacity. When limited to Child-Pugh B and C liver cirrhosis patients, a ≥ 75% reduction of PVT volume improved the prognosis.ConclusionsDanaparoid sodium-based anticoagulation therapy was effective and safe for PVT in patients with cirrhosis. Return of plasma AT-III level to the normal range during the treatment period contributes to reduction of PVT volume. A reduction of ≥75% in PVT volume may improve the prognosis of Child-Pugh B and C decompensated cirrhosis patients with PVT.

Low levels of coagulation inhibitors: a high-risk thrombotic factor in thalassemic patients

Background and aimThe β-thalassemia major (β-TM) is defined as a hereditary red blood cell (RBC)- related disease. Thrombotic events are associated with thalassemia in adult patients. Thus, the present investigation was aimed to examine some hemostatic parameters, including anti thrombin- III (AT-III), protein-C (PRC) and protein-S (PRS) in β-TM patients. MethodsThirty B-TM patients who referred for routine follow-up admission to the thalassemia clinic of Kerman Special Disease Center alongside with 30 healthy subjects were selected and enrolled in the present study. Further registration, the peripheral blood specimens were collected after 3 weeks of last transfusion and then the plasma concentrations of AT-III, PRC and PRS were measured in them. ResultsWe have observed that the concentrations of natural coagulation inhibitors (PRC and PRS) were significantly attenuated in β-TM patients (P < 0.05), while the plasma level of AT-III was not remarkably differed in β-TM patients in compare to healthy subjects. ConclusionAccording to the findings of present work, significant changes in the PRC, PRS and AT-III which could be observed in multi transfused β-TM patients may attribute as critical risk factors for the development of upcoming thromboembolic events in their future life.

Identification of molecular markers for pre-thrombotic state: validation in the rabbits with tibia fracture or lung cancer

Background: Currently there is no reports on identifying molecular markers for pre-thrombotic state in animal experimental settings. It’s necessary to explore the potential molecular markers for pre-thrombotic state to provide evidence for the pharmacotherapy of venous thromboembolism (VTE). Methods: A total of 36 male rabbits were randomly divided into Sham, Tibia fracture, Lung cancer, Tibia fracture and lung cancer group. Pro-thrombin time (PT), thrombin time (TT), activated partial pro-thrombin time (APTT), fibrinogen (FIB), D-dimer (D-D) and anti-thrombin III (AT-III) at baseline, 1, 7, 14 and 21 days after operation were detected. Immuno-histochemical staining of tumor tissue sections was performed to observe the expression of CD31, VEGF and vWF. Western blot and qPCR were used to detect the expression levels of ANG and VEGF gene in tumor tissues. Furthermore, we analyzed the tumor tissue with HE staining, immunochemistry, qPCR and Western blot. all the data were statistically analyzed with GraphPad Prism 6. Results: There were 0, 1, 2, 4 cases of VTE in sham, tibia fracture, lung cancer, tibia fracture and lung cancer group respectively. The level of PT, APTT, TT and AT-III were significantly decreased after operation (all P<0.05), whereas the level of FIB and D-D were significantly increased after operation (all P<0.05). The level of PT, APTT, TT and AT-III were gradually decreased in tibia fracture, lung cancer, tibia fracture and lung cancer group respectively (all P<0.05), while the level of FIB and D-D were gradually increased in tibia fracture, lung cancer, tibia fracture and lung cancer group respectively (all P<0.05). The medullary lymphocytes increased significantly in the lung cancer group, tibia fracture and lung cancer group (all P<0.05), and the number of medullary lymphocytes in tibia fracture and lung cancer group is significantly higher than that of lung cancer group (P<0.001). The expression of CD31, VEGF and vWF in Tibia fracture and lung cancer group is significantly higher than that of lung cancer group (all P<0.001). The expression ANG and VEGF in tibia fracture and lung cancer group is significantly higher than that of lung cancer group (all P<0.01). Conclusions: PT, TT, APTT, FIB, D-D and AT-III seem to be sensitive molecular markers for identifying the pre-thrombotic state. CD31, VEGF, ANG and vWF play an important role in the progression of the pre-thrombotic state.

Bajos niveles de inhibidores de la coagulación: un factor de alto riesgo trombogénico en pacientes talasémicos

Background and aimThe β-thalassemia major (β-TM) is defined as a hereditary red blood cell-related disease. Thrombotic events are associated with thalassemia in adult patients. Thus, the present investigation was aimed to examine some hemostatic parameters, including anti thrombin-III (AT-III), protein-C (PRC) and protein-S (PRS) in β-TM patients. MethodsThirty B-TM patients who referred for routine follow-up admission to the thalassemia clinic of Kerman Special Disease Center alongside with 30 healthy subjects were selected and enrolled in the present study. Further registration, the peripheral blood specimens were collected after 3 weeks of last transfusion and then the plasma concentrations of AT-III, PRC and PRS were measured in them. ResultsWe have observed that the concentrations of natural coagulation inhibitors (PRC and PRS) were significantly attenuated in β-TM patients (P<0.05), while the plasma level of AT-III was not remarkably differed in β-TM patients in compare to healthy subjects. ConclusionAccording to the findings of present work, significant changes in the PRC, PRS and AT-III which could be observed in multi transfused β-TM patients may attribute as critical risk factors for the development of upcoming thromboembolic events in their future life.