Predictors of Bleeding from Esophageal Varices: The Role of Factor VII and von Willebrand Factor (vWF)

Objectives: Bleeding from gastroesophageal varices is the most serious and life-threatening complication of cirrhosis and accounts for 10% of all cases of bleeding from the upper GI tract. It is essential to identify and treat those patients at the highest risk because each episode of variceal hemorrhage carries a 20 percent to 30 percent risk of death, and up to 70 percent of patients who do not receive treatment die within one year of the initial bleeding episode. The aim of this study is to determine the clinical predictors of bleeding esophageal varices and study the role of F VII (factor VII) and vWF (von willebrand factor) in predicting bleeding in patients with eosphogeal varices. Methods: A case control study was done on all patients with esophageal varices admitted at Sohag and Qena faculty of medicine hospitals from January 2012 to August 2013. Various clinical, laboratory and endoscopic variables were tested to determine the predictors of esophageal bleeding. Results: Among 300 patients with esophageal varices, 80 percent was due to hepatitis C virus (HCV), 18 percent was due to hepatitis B virus (HBV), and 2 percent had both HCV and HBV. As an etiologic factor for their liver disease, hemoglobin was 10.12 ± 2.26 g/l, platelet count 135.55 ± 65.94 × l09/l, prothrombin time 14.1 ± 0.92 second, albumin 2.88 ± 0.71 g/dl, ALT 48.25 ± 24.15 u/l, total bilirubin 1.92 ± 1.36 mg/dl. Factor VII was 27.4 ± 8.92 percent and vWF was 188.33 ± 13.66 IU/dl. Splenomegaly was reported 79.6 percent, 90.3 percent had ascites. 35 percent had grade III esophageal varices, 29 percent had four-column esophageal varices on endoscopy, 13.7 percent had concomitant gastric varices and 38.3 percent had portal hypertensive gastropathy. Platelet count, presence of red color sign, the number of columns of esophageal varices, presence of portal gastropathy on eosphagogastroduodenoscopy (EGD) showed a significant positive correlation with bleeding. There is a significant decrease of FVII and a significant increase of vWF in bleeding group in comparison with non bleeding group. Conclusion: Thrombocytopenia, presence of encephalopathy and endoscopic findings of large varices, presence of red color sign, and portal hypertensive gastropathy were found to be predictors of esophageal variceal bleeding. Increase of vWF and decrease of FVII are laboratory predictors of esophageal variceal bleeding.

改良墨汁灌注法与von Willebrand factor免疫荧光法在大鼠视网膜微血管形态显示中的对比研究

目的:比较改良墨汁灌注法与von Willebrand factor(vWf)免疫荧光法在大鼠视网膜微血管形态显示方面的异同。方法:成年健康SD大鼠随机分成vWf免疫荧光显色组和改良墨汁灌注组。改良墨汁灌注组分两步灌注明胶墨汁40 ml。vWf免疫荧光显色组常规灌注生理盐水40 ml。视网膜行铺片和切片,观察vWf免疫荧光法和改良的墨汁灌注法显示的微血管形态;两组视网膜切片还进行NeuN、Parvalbumin和GFAP的免疫组织化学显色。结果:vWf免疫荧光法能充分显示视网膜铺片周围部的微血管,但对铺片中央部和切片的微血管显示不良;改良墨汁灌注法能充分显示大鼠视网膜铺片和切片的微血管,用此方法灌注的视网膜切片的NeuN、Parvalbumin和GFAP免疫组织化学效果均与正常视网膜相似。结论:改良墨汁灌注法在大鼠视网膜微血管形态显示中优于vWf免疫荧光法,且能在同一切片上准确显示血管与神经元/胶质细胞的空间关系。

重度创伤性颅脑损伤后凝血功能障碍患者血浆α2-抗纤溶酶、vWF及ET-1水平及其影响因素分析

目的探讨重度创伤性颅脑损伤(TBI)后凝血功能障碍患者血浆α2-抗纤溶酶(α2-AP)、血管性血友病因子(vWF)及内皮素-1(ET-1)水平变化及影响因素。方法回顾性分析2021年1月—2022年12月南阳市第一人民医院神经外科和新乡市中心医院神经外科收治的106例重度TBI患者。其中男性58例,女性48岁;年龄32~60岁,平均43.7岁。根据TBI后24 h内是否发生凝血功能障碍分为凝血正常组(74例)和凝血障碍组(32例)。比较两组重度TBI患者临床资料和入院次日清晨的凝血功能指标及血浆α2-AP、vWF、ET-1水平;Pearson相关性分析重度TBI后凝血功能障碍患者血浆α2-AP、vWF、ET-1水平与凝血功能指标的关系;Logistic回归性分析影响重度TBI患者发生凝血功能障碍的危险因素;受试者工作特征(ROC)曲线分析血浆α2-AP、vWF、ET-1水平对重度TBI患者发生凝血功能障碍的预测价值。结果两组患者年龄、入院GCS、入院头部最高AIS和入院时平均MAP比较,差异有统计学意义[(45.4±5.7)岁vs.(42.8±4.2)岁、(6.7±1.1)分vs.(7.2±0.9)分、(4.6±0.8)分vs.(3.7±0.6)分、(84.1±11.2)mmHg vs.(91.0±9.7)mmHg],P<0.05。凝血障碍组TBI患者PT、APTT和INR等凝血功能指标水平和血浆α2-AP、vWF、ET-1水平高于凝血正常组,纤维蛋白原(FIB)水平低于凝血正常组[(27.9±3.4)s vs.(12.0±1.9)s、(66.4±5.8)s vs.(36.2±2.3)s、1.6±0.2 vs.1.0±0.1、(67.8±8.2)mg/L vs.(19.3±2.4)mg/L、(162.5±24.6)%vs.(94.8±10.4)%、(65.1±5.2)mg/L vs.(41.6±3.9)mg/L、(2.6±0.3)g/L vs.(3.9±0.5)g/L,差异有统计学意义(P<0.05)。Pearson相关性分析,重度TBI后凝血功能障碍患者血浆α2-AP、vWF、ET-1与PT呈强正相关(r=0.723、0.528、0.586,P<0.05),与APTT呈强正相关(r=0.646、0.572、0.585,P<0.05),与INR呈强正相关(r=0.592、0.507、0.548,P<0.05),与FIB呈强负相关(r=-0.653、-0.672、-0.526,P<0.05);Logistic回归分析显示,入院时GCS降低(OR=2.593,95%CI:1.018~6.606,P<0.05)、α2-AP水平升高(OR=3.019,95%CI:1.107~8.236,P<0.05)和vWF水平升高(OR=2.729,95%CI:1.028~7.243,P<0.05)为重度TBI患者发生凝血功能障碍的相关危险因素;ROC曲线显示,α2-AP、vWF、ET-1预测重度TBI患者发生凝血功能障碍的AUC分别为0.887(95%CI:0.805~0.969,P<0.05)、0.828(95%CI:0.734~0.922,P<0.05)和0.807(95%CI:0.695~0.918,P<0.05),联合检测的AUC为0.912(95%CI:0.854~0.970,P<0.05),灵敏度为91.67%,特异度为87.14%。结论重度TBI后凝血功能障碍患者血浆α2-AP、vWF和ET-1水平均显著升高,其中血浆α2-AP、vWF水平升高为重度TBI患者发生凝血功能障碍的相关危险因素。

固相基质表面von Willebrand Factor抗体的固定化研究

以丝素蛋白膜和聚乳酸膜为基质,采用辉光放电等离子体处理技术和共价交联的方法对vonWillebrand factor(vWf)抗体进行了固定化研究。利用抗体过剩法和酶联免疫实验对固定化效率进行了评价,固定化抗体的活性采用体外凝血时间(APTT,TT和PT)测定进行检测。结果显示固定化效率最高可以达到23.88%,酶联免疫实验均显示阳性,APTT、TT项有明显延长,有的还超出了仪器的测量范围,由此说明,通过这种方法可以有效地对vWf抗体进行共价固定化。本研究拓宽了抗体固定化技术的应用范围,为血管性假血友病的早期快速诊断仪器或试剂盒的研制打下技术基础,同时为其它凝血因子抗体相关的生物材料研究与开发提供一种新思路。

血清vWF、Treg相关细胞因子在急性白血病患儿危险分层及疗效评估中的价值

目的探究血清血管性血友病因子(vWF)、调节性T细胞(Treg)相关细胞因子[转化生长因子-β(TGF-β)、白介素-10(IL-10)、白介素-35(IL-35)]在急性白血病(AL)患儿危险分层及疗效评估中的价值,为AL患儿临床诊疗提供参考。方法选取2020年2月至2022年8月郑州大学第三附属医院收治的78例AL患儿,根据CCLG-ALL-2018方案危险分层分为低危组(39例)、中危组(21例)、高危组(18例)3个亚组,分别比较不同类型、不同危险分层患儿血清vWF、TGF-β、IL-10、IL-35水平,并进行相关性分析。AL患儿均接受规范化治疗,根据治疗1 a疗效评估结果分为临床有效组(完全缓解+部分缓解,62例)、临床无效组(未缓解,16例),分别比较两组治疗2、6个月血清vWF、TGF-β、IL-10、IL-35水平,分析其对AL患儿疗效的预测价值。结果低危组血清vWF、IL-10、IL-35水平低于中危组,中危组血清vWF、IL-10、IL-35水平低于高危组(P<0.05);低危组血清TGF-β水平高于中危组,中危组血清TGF-β水平高于高危组(P<0.05);Spearman相关系数法分析显示,血清vWF、IL-10、IL-35与AL患儿危险分层呈正相关,血清TGF-β与AL患儿危险分层呈负相关(P<0.05);78例AL患儿经1 a治疗后有28例完全缓解、34例部分缓解,计入临床有效组(62例),16例未缓解,计入临床无效组(16例)。治疗2、6个月临床有效组血清vWF、IL-10、IL-35水平均低于临床无效组,血清TGF-β水平高于临床无效组,差异有统计学意义(P<0.05);治疗2、6个月各血清指标联合预测AL患儿临床无效的曲线下面积分别为0.875、0.933(P<0.05)。结论血清vWF、TGF-β、IL-10、IL-35与AL患儿危险分层及疗效有关,动态监测血清vWF、Treg相关细胞因子有利于病情及疗效评估。

视网膜静脉阻塞患者血清FABP4,VWF和LCN-2水平表达与继发黄斑水肿程度及预后的关系研究

目的 探究视网膜静脉阻塞(retinal vein obstruction,RVO)患者血清脂肪细胞型脂肪酸结合蛋白(fatty acid-binding protein 4,FABP4)、血管性假血友病因子(von willebrand factor,VWF)、脂质运载蛋白2(lipocalin-2,LCN-2)水平表达与继发黄斑水肿(macular edema,ME)程度及预后的关系研究。方法 选取2021年1月~2023年8月来西北大学附属第一医院治疗的98例确诊的RVO继发ME患者为观察组,根据黄斑水肿程度分为重度组(n=46)、中度组(n=32)和轻度组(n=20),根据预后情况分为预后不良组(n=36)和预后良好组(n=62);另选取98例单纯RVO患者为对照组。比较各组血清FABP4,VWF,LCN-2水平;多因素Logistic回归分析RVO继发ME患者发生预后不良的影响因素;ROC曲线分析血清FABP4,VWF和LCN-2水平对RVO继发ME患者发生预后不良的预测价值。结果 与对照组相比,观察组血清FABP4(35.24±4.43 ng/ml vs 23.19±3.69 ng/ml),VWF(2.67±0.67 ng/ml vs1.48±0.38 ng/ml),LCN-2(112.53±12.74 mg/L vs 85.49±9.86 mg/L)水平明显升高,差异具有统计学意义(t=20.690,15.294,16.616,均P<0.05);随病情逐渐发展,轻、中、重度组血清FABP4(33.38±4.29 ng/ml,35.79±4.49 ng/ml,38.64±4.65 ng/ml),VWF(2.36±0.59 ng/ml,2.72±0.66 ng/ml,3.29±0.87 ng/ml),LCN-2(105.84±12.24 mg/L,114.61±12.88 mg/L,124.59±13.69 mg/L)水平逐渐升高,差异具有统计学意义(F=10.194,13.294,15.703,均P<0.05);与预后良好组相比,预后不良组血清FABP4(39.64±4.59 ng/ml vs 32.69±4.34 ng/ml),VWF(3.26±0.87ng/ml vs 2.33±0.55 ng/ml),LCN-2(124.56±13.42 mg/L vs 105.54±12.34 mg/L)水平明显升高,差异具有统计学意义(t=7.482,6.487,7.122,均P<0.05));血清FABP4(OR=2.236,95%CI:1.109~4.510),VWF(OR=2.069,95%CI:1.044~4.100),LCN-2(OR=1.875,95%CI:1.015~3.463)为RVO继发ME患者发生预后不良的独立危险因素(均P<0.05);血清FABP4,VWF,LCN-2水平预测患者发生预后不良的AUC(95%CI)分别为0.817(0.726~0.888),0.791(0.697~0.867)和0.798(0.705~0.872),三者联合预测的AUC为0.932(0.863~0.973),三者联合预测优于各因子单独预测(Z=2.034,2.375,2.385,P=0.042,0.018,0.017)。结论 RVO继发ME患者血清FABP4,VWF和LCN-2水平均上调,且均为患者发生预后不良的独立危险因素,三者联合检测对RVO继发ME患者发生预后不良具有更高的预测价值。

Clinical significance of plasma D-dimer and von Willebrand factor levels in patients with ulcer colitis

AIM: To investigate the levels of D-dimer(DD) and von Willebrand factor(vWF) and the relationship between DD and vWF in ulcerative colitis(UC) patients. METHODS: A total of 29 plasma specimens were obtained from patients with ulcerative colitis (male 13, female 16) aged 21-47 years (33+/-11). Disease activity was assessed by Truelove-Writeria. Patients with a score of above 5 were regarded as having active colitis. Twenty healthy people(male 12, female 8) aged 19-53 years(31+/-14) served as normal controls. Blood samples were taken from an antecubital vein puncture. Blood(1.8 mL) was injected into the tubes containing sodium citrate (0.13 mmol/L). The plasma was obtained by centrifugation at 3000 r.min(-1) for 10 min, and stored at -80 degrees until assayed by ELISA. RESULTS: The mean plasma levels of DD and vWF in active UC patients were significantly higher than those of the controls (0.69+/-0.41 vs 0.27+/-0.11, P【0.01 143+/-46 vs 103+/-35, P【0.01). The mean plasma levels of DD in the patients with active disease were higher than those with inactive disease(0.69+/-0.41 vs 0.48+/-0.29 P【0.05). The levels of vWF were not different between active and inactive patients. DD levels were positively related to vWF levels( r =0.574, P【0.01). There was no significant difference between levels of DD and vWF and the scope of disease and sex of the patients. CONCLUSION: vWF is an important feature and a good marker of UC intravascular thrombus and endothelial cell dysfunction were found in UC patients and the combined test of DD and vWF is helpful to distinguish the activity of the UC patients.

Plasma von Willebrand factor level as a prognostic indicator of patients with metastatic colorectal carcinoma

AIM:To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with historically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using X2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables. RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P<0.05). Moreover, higher vWF plasma levels were associated with advanced tumor stage (P<0.05) and the presence of multiple metastases (P=0.014). Patients with lower vWF plasma levels (≤160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P= 0.0043). By multivariate analysis, plasma vWF levels (P<0.001), the extent of metastasis (P= 0.012), and the performance status (P=0.014) were identified as independent prognostic factors. CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.

Von Willebrand Factor Antigen and ADAMTS13 Activity Assay in Pregnant Women and Severe Preeclamptic Patients

The present study examined von Willebrand factor (vWF) levels and ADAMTS13 activity in pregnant and severe preeclamptic women in order to shed light on the prothrombotic state in severe preeclampsia.Thirty healthy women of childbearing age,22 second trimester pregnant women,30 third trimester pregnant women and 10 severe preeclamptic patients were recruited in this study.ADAMTS13 activity was determined by the FRETS-vWF73 assay and vWF antigen (vWF:Ag) levels by an enzyme-linked immunosorbent assay.The results showed that there were statistically significant differences in plasma vWF antigen levels between the severe preeclamptic and third trimester pregnant women,between third and second trimester pregnant women (P【0.05).The third trimester pregnant women had significantly lower plasma ADAMTS13 activity than second trimester pregnant women (P【0.05).Nevertheless,no significant differences in plasma ADAMTS13 activity were found between severe preeclamptic patients and the third trimester pregnant women (P】0.05).In conclusion,plasma ADAMTS13 activity is normal in severe preeclampsia despite the increased vWF:Ag levels.Prothrombotic state is involved in the pathogenesis of severe preeclampsia,as a result of endothelial injury.

Elevated plasma von Willebrand factor levels in patients with active ulcerative colitis reflect endothelial perturbation due to systemic inflammation

AIM: To evaluate the plasma von Willebrand factor (vWF) levels in patients with ulcerative colitis (UC) and to investigate their relationship with disease activity,systemic inflammation and coagulation activation.METHODS: In 46 patients with ulcerative colitis (active in 34 patients), clinical data were gathered and plasma vWF levels, markers of inflammation (ESR, CRP, and fibrinogen) and thrombin generation (TAT, F1+2, and D-dimers) were measured at baseline and after 12 wk of treatment. Plasma vWF levels were also determined in 52 healthy controls (HC). The relationship of plasma vWF levels with disease activity, disease extent, response to therapy, acute-phase reactants (APRs) and coagulation markers (COAGs) was assessed.RESULTS: The mean plasma vWF concentrations were significantly higher in active UC patients (143.38±63.73%) than in HC (100.75±29.65%, P = 0.001)and inactive UC patients (98.92±43.6%, P = 0.031).ESR, CRP and fibrinogen mean levels were significantly higher in active UC patients than in inactive UC patients,whereas there were no significant differences in plasma levels of D-dimers, F1+2, and TAT. UC patients with raised APRs had significantly higher mean plasma vWF levels than those with normal APRs (144.3% vs 96.2%,P = 0.019), regardless of disease activity. Although the mean plasma vWF levels were higher in UC patients with raised COAGs than in those with normal COAGs,irrespective of disease activity, the difference was not significant (141.3% vs 118.2%, P = 0.216). No correlation was noted between plasma vWF levels and disease extent. After 12 wk of treatment, significant decreases of fibrinogen, ESR, F1+2, D-dimers and vWF levels were noted only in UC patients with clinical and endoscopic improvement.CONCLUSION: Our data indicate that increased plasma vWF levels correlate with active ulcerative colitis and increased acute-phase proteins. Elevated plasma vWF levels in ulcerative colitis possibly reflect an acutephase response of the perturbed endothelium due to inflammation. In UC patients, plasma vWF levels may be another useful marker of disease activity or response to therapy.

Levels and activities of von Willebrand factor and metalloproteinase with thrombospondin type-1 motif, number 13 in inflammatory bowel diseases

To evaluate the levels of von Willebrand factor (VWF) and metalloproteinase with thrombospondin type-1 motif, number 13 (ADAMTS13) in inflammatory bowel disease (IBD) and correlate them with the disease activity. METHODSConsecutive patients with IBD aged 18 years or older were enrolled in the study. Forty-seven patients with ulcerative colitis (UC), 38 with Crohn’s disease (CD), and 50 healthy controls were included. The white blood cell count, haematocrit, platelet count, fibrinogen, partial activated thromboplastin time, C-reactive protein, albumin, VWF antigen level (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen-binding activity (VWF:CB), and ADAMTS13 antigen level (ADAMTS13:Ag) and activity (ADAMTS13act) were measured. The following ratios were assessed: VWF:RCo/VWF:Ag, VWF:CB/VWF:Ag, VWF:Ag/ADAMTS13act, and ADAMTS13act/ADAMTS13:Ag. RESULTSCompared to controls, the odds ratio (OR) of an elevated VWF: Ag > 150% was 8.7 (95%CI: 2.7-28.1) in the UC group and 16.2 (95%CI: 4.8-54.0) in the CD group. VWF:CB was lower in UC patients, and active CD was associated with a higher VWF: RCo (+38%). The ORs of VWF:CB/VWF:Ag < 0.7 (a marker of acquired von Willebrand syndrome) in the UC and CD groups were 11.9 (95%CI: 4.4-32.4) and 13.3 (95%CI: 4.6-38.1), respectively. Active UC was associated with lower ADAMTS13:Ag (-23%) and ADAMTS13act (-20%) compared to UC in remission. Patients with active CD had a 15% lower ADAMTS13act than controls. The activity of UC, but not that of CD, was inversely correlated with ADAMTS13:Ag (r = -0.76) and ADAMTS13act (r = -0.81). CONCLUSIONComplex VWF-ADAMTS13-mediated mechanisms disturb haemostasis in IBD. A reduced WVF:CB is a risk factor for bleeding, while a lower ADAMTS13 level combined with an elevated VWF:Ag could predispose one to thrombosis.

Expression patterns of plasma von Willebrand factor and serum interleukin-8 in patients with early-stage severe pulmonary contusion

BACKGROUND： von Willebrand factor （vWF） is only released from endothelial cells and platelets and is an in vivo and in vitro marker of endothelial injury in septic patients with acute lung injury （ALI）. Interleukin-8 （IL-8）, as a proinflammatory mediator causing recruitment of inflammatory cells, induces an increase in oxidant stress mediators and makes it as a key parameter for localized inflammation. However, it has not been well established whether the level of serum IL-8 is associated with the severity of lung injury and whether it is a prognosis marker for severe lung contusion. This study was to investigate the expression of plasma vWF and IL-8 and their association with the severity and outcomes of severe pulmonary contusion.METHODS： A total of 63 patients were divided into a severe pulmonary contusion with acute respiratory distress syndrome （ARDS） group and a non-ARDS group, or a survivor group and a non- survivor group, or an injury severity score （ISS） 〈20 group and an ISS 〉20 group. Another 20 healthy volunteers served as controls. The levels of plasma vWF and serum IL-8 were measured by enzyme- linked immunosorbent assay （ELISA） at 1,3, 5 and 7 days after injury. The expression patterns of the plasma vWF and serum IL-8 were compared between different groups. RESULTS： The concentrations of plasma vWF and serum IL-8 were significantly increased in all severe pulmonary contusion patients at all time points in comparison with the control group. The concentrations of plasma vWF in patients with ARDS increased during the whole study period, but vWF in patients with non-ARDS increased gradually until day 5 and then decreased at day 7. The concentration of serum IL-8 showed a similar expression pattern in both groups, but the expression increased more significantly in the ARDS group than in the non-ARDS group. Interestingly, both plasma vWF and serum IL-8 levels steadily increased in the non-survivor group. Furthermore, the level of plasma vWF was higher in the ISS〉20 group than in the ISS〈20 group. The level of serum IL-8 in the ISS〉20 group was consistently high, while that in the ISS〈20 group peaked at day 3 and decreased at day 5. In addition, the level of plasma vWF was positively correlated with platelet count, but negatively correlated with oxygen index. The level of serum IL-8 was positively correlated with white blood cell count and ISS score, and inversely correlated with oxygen index. CONCLUDION： The elevated levels of plasma vWF and serum IL-8 in severe pulmonary contusion patients reflect the severity of pulmonary injury and patients outcomes, suggesting that the plasma vWF and serum IL-8 are sensitive markers for clinical evaluation of the severity of pulmonary injury and predication of patient prognosis.

von Willebrand factor antigen as a therapeutic target of portal hypertension in cirrhosis

Increased thrombotic potential within the liver sinusoids due to local endothelial production of von Willebrand factor antigen macromolecules could represent an additional therapeutic target of portal hypertension in patients with cirrhosis. In this case, anti-inflammatory and antithrombotic drugs could modulate portal pressure by preventing the formation of intrahepatic platelet-induced microthrombi.

ADAMTS13 and von Willebrand factor are useful biomarkers for sorafenib treatment efficiency in patients with hepatocellular carcinoma

BACKGROUND Many advanced hepatocellular carcinoma(HCC) patients are receiving sorafenib treatment. Sorafenib reportedly improves overall survival(OS) significantly in patients with HCC. Prediction of sorafenib response and prognosis in patients with HCC receiving sorafenib treatment are important due to the potentially serious side effects of sorafenib. A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) and von Willebrand factor(VWF) are associated with the pathophysiology of liver cirrhosis and HCC through their roles in hypercoagulability; they are also associated with angiogenesis via vascular endothelial growth factor(VEGF). The imbalance between ADAMTS13 and VWF was associated with prognosis of various cancers in patients undergoing chemotherapy.AIM To investigate ADAMTS13 and VWF as potential biomarkers for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.METHODS Forty-one patients with HCC receiving sorafenib treatment were included in this study. The initial daily sorafenib dose was 400 mg in all patients. ADAMTS13 activity(ADAMTS13:AC), VWF antigen(VWF:Ag), VEGF levels were determined by enzyme-linked immunosorbent assay. Univariate andmultivariate analyses were used to determine predictive factors for sorafenib response and prognosis in patients with HCC receiving sorafenib treatment.RESULTS ADAMTS13:AC was significantly higher in patients with stable disease(SD),partial response(PR), and complete response(CR) than in those with progressive disease(PD)(P < 0.05). In contrast, VWF:Ag and the VWF:Ag/ADAMTS13:AC ratio were significantly lower in patients with SD, PR, and CR than in those with PD(P < 0.05 for both). Multivariate analysis showed that the VWF:Ag/ADAMTS13:AC ratio was the only predictive factor for sorafenib response and ADAMTS13:AC was the only prognostic factor in patients with HCC receiving sorafenib treatment. The patients with a low ADAMTS13:AC(<78.0) had significantly higher VEGF levels than those with a high ADAMTS13:AC(≥ 78.0)(P < 0.05).CONCLUSION The VWF:Ag/ADAMTS13:AC ratio and ADAMTS13:AC are potentially useful biomarkers for sorafenib response and prognosis, respectively, in patients with HCC receiving sorafenib treatment.

Effect of Tongmai Jiangzhi Oral Liquid (通脉降脂口服液) on Serum P-selectin, von Willebrand Factors and D-Dimer in Patients with Atherosclerosis

Objective: To explore the role of cytokines on the pathogenesis of atherosclerosis, and the effect of Tongmai Jiangzhi oral liquid (通脉降脂口服液,TMJZ) on cytokines through observing serum P-se-lectins (Ps), von Willebrand (vWF), and D-dimer (D-D) in atherosclerosis (AS) patients. Methods: Sixty-three AS patients were randomly divided into the treated group (n = 33, treated with TMJZ, 10 ml each time, three times a day) and the control group (n = 30, treated with Lovastatin, 10 mg, once daily). The levels of serum lipids (enzymatic methods), Ps, vWF, and D-D were measured before and after 8 weeks of treatment. Results: Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), apo-protein B-100 (apoB-100) were significantly decreased (P<0.05 or P< 0.01) and high-density lipoprotein cholesterol (HDL-C) was significantly raised (P<0.05) after TMJZ treatment. Serum Ps, vWF, and D-D also declined (P<0.05) after treatment. There was no significant difference between the treated and the control groups in these parameters except serum HDL-C level. Conclusion: TMJZ has good therapeutic effect in regulating serum lipids, improving endothelial cell function, inhibiting activation of platelets, and preventing the disturbance of blood coagulation/fibrinolysis function in patients with AS.

Comments on:Perioperative von Willebrand factor dynamics are associated with liver regeneration and predict outcome after liver resection

Recentlythearticle"PerioperativevonWillebrandfactordynamics are associated with liver regeneration and predict outcome afterliver resection" was published in Hepatology[1].Prof.Starlinger et al. aimed to assess the association of von Willebrand factor (vWF) levels and clinical outcome in patients with liver cancers post-liverresection(LR).Basedonthemechanismthatplatelets accumulation in the liver may promote liver regeneration after partial LR in mice, they found the vWF-dependent pattern of platelets accumulationduringliverregenerationinpatientsaftersurgery.

Role of von Willebrand factor levels in the prognosis of stage Ⅳ colorectal cancer: Do we have enough evidence?

Cancer patients usually present a prothrombotic condition. Several clotting-related proteins, such as von Willebrand factor （vWF）, presenting higher plasma concentrations in these patients, may play a key role in this process. Moreover, some of those proteins are currently being characterized as response rate and overall survival markers in metastatic colorectal cancer （MCRC）. In this comment article,

寻常型银屑病患者血清TARC、vWF水平与病情严重程度的相关性

目的 检测并分析寻常型银屑病(PV)患者血清胸腺和活化调节趋化因子(TARC)、血管性血友病因子(vWF)水平及与病情严重程度的相关性。方法 选取2020年2月至2022年2月沧州市人民医院收治的74例PV患者(PV组),以本院同期42例健康体检者为对照组。根据病情严重程度将PV患者分为轻中度组(40例)和重度组(34例)。收集患者临床资料,采用ELISA法检测血清TARC、vWF、TNF-α和IL-8水平。比较不同病情严重程度PV患者血清TARC、vWF、TNF-α、IL-8水平及临床指标的差异。采用Pearson相关分析PV患者血清TARC、vWF与临床指标的相关性。采用logistic回归分析重度PV发生的影响因素。采用ROC曲线评估血清TARC、vWF对重度PV的诊断效能。结果 PV组血清TARC、vWF水平均高于对照组,差异均有统计学意义(均P<0.05)。重度组PV患者血清TARC、vWF、WBC、中性粒细胞计数、ESR、银屑病皮损面积和严重程度评分(PASI)、超敏C反应蛋白(hs-CRP)、TNF-α、IL-8均高于轻中度组,差异均有统计学意义(均P<0.05)。PV组患者血清TARC、vWF水平与ESR、hs-CRP、PASI评分、TNF-α、IL-8均呈显著正相关(均P<0.05)。血清TARC、vWF水平升高是重度PV发生的独立危险因素。血清TARC、vWF联合诊断发生重度PV的AUC为0.903,显著高于TARC和vWF单独诊断的0.823和0.807(均P<0.05)。血清TARC、vWF联合诊断发生重度PV的灵敏度和特异度为0.878和0.753。结论 PV患者血清TARC、vWF水平升高。两者与PV病情严重程度呈正相关,血清TARC、vWF联合检测有助于评估PV疾病严重程度。

Reliability of Plasma Von Willebrand Factor Antigen in Prediction of Esophageal Varices in Patients with Liver Cirrhosis

Background: Bleeding esophageal varices (OVs) due to portal hypertension are one of the major complications with high mortality in liver cirrhosis. So, early detection and management are mandatory. Aim: To evaluate the role of Von Willebrand factor (VWF) in predicting the presence of OVs. Patients and Methods: 62 patients with liver cirrhosis representing different Child-Pugh classes were included. The diagnosis of liver cirrhosis was based on the combination of clinical, laboratory and US examinations. All included patients underwent the following investigations: complete blood count, liver function tests (ALT, AST, serum bilirubin, albumin and total protein, prothrombin time (PT) and concentration (PC), INR and serum alkaline phosphatase), serum creatinine, Von Willebrand factor antigen (VWF-Ag) measurement and abdominal US. Upper endoscopic evaluation was done to detect presence or absence of varices (esophageal or gastric) and/or PHG. Results: 38 males and 24 females with their mean age (46 ± 12 years old) were included. Plasma Von Willebrand factor-Ag level was significantly higher in patients with OVs than those without varices (P value = 0.000). Also, its level was significantly higher in patients with higher grade of OVs, G3 than those with G1 or G2 (P value = 0.000). Patients with large OVs including those with G2 and G3 showed significantly higher values of VWF than those with small OVs (NO and G1) (P value = 0.000). VWF was independent predictor for detecting the presence of OVs with good sensitivity (90), specificity (77.3) and accuracy (85.5) at a cutoff value of 1.74 U/ml. Also it was an independent predictor for detecting the presence of large OVs with good sensitivity (91.2), specificity (85.7) and accuracy (88.7) at a cutoff value of 2.16 U/ml. Conclusion: VWF-Ag could be used as a non invasive laboratory independent predictor for the detection of OVs.

老年2型糖尿病合并非酒精性脂肪肝患者血清vWF、sST2水平与胰岛素抵抗及肝功能的相关性分析

目的探究老年2型糖尿病(T2DM)合并非酒精性脂肪肝(NAFLD)患者血清血管性血友病因子(vWF)、可溶性生长刺激因子2(sST2)水平与胰岛素抵抗及肝功能的相关性。方法选取2020年4月至2022年4月我院收治的116例确诊为老年T2DM合并NAFLD患者为患病组,根据肝功能等级,将其分为A级组(41例)、B级组(39例)和C级组(36例);根据是否存在胰岛素抵抗,将其分为抵抗组(42例)和非抵抗组(74例)。选取我院同期收治的单纯T2DM患者116例作为对照组。比较各组血清vWF、sST2水平;多因素Logistic回归分析老年T2DM合并NAFLD的影响因素;受试者工作特征(ROC)曲线分析血清vWF、sST2水平对T2DM合并NAFLD的诊断价值。结果患病组肥胖人数占比、HOMA-IR评分、BMI、饮酒史人数占比、低密度脂蛋白胆固醇、总胆固醇、三酰甘油、vWF、sST2水平均高于对照组,而总胆红素低于对照组(P<0.05);随着肝功能等级增加,血清vWF、sST2水平逐渐升高(P<0.05);抵抗组血清vWF、sST2水平高于非抵抗组(P<0.05)。饮酒史、低密度脂蛋白胆固醇、总胆固醇、三酰甘油、HOMA-IR、vWF、sST2为老年T2DM合并NAFLD的独立危险因素,总胆红素为独立保护因素(P<0.05)。血清vWF、sST2水平诊断T2DM合并NAFLD的曲线下面积(AUC)分别为0.870、0.866,截断值分别为24.05 ng/ml、20.28 ng/ml,二者联合诊断的AUC为0.940,二者联合诊断优于各指标单独诊断(Z_(二者联合-vWF)=2.056、Z_(二者联合-sST2)=2.417,P=0.040、0.016)。结论老年T2DM合并NAFLD患者血清vWF、sST2水平均上调,且vWF、sST2与胰岛素抵抗及肝功能密切相关,二者联合对老年T2DM合并NAFLD具有较高的诊断价值。