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

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World Journal of Gastrointestinal Oncology 2019年第5期11卷 424-435页

作者： Hiroaki Takaya Tadashi Namisaki Naotaka Shimozato Kosuke Kaji Mitsuteru Kitade Kei Moriya Shinya Sato Hideto Kawaratani Takemi Akahane Masanori Matsumoto Hitoshi Yoshiji Third Department of Internal Medicine Nara Medical University Department of Blood Transfusion Medicine Nara Medical University

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 *** To investigate ADAMTS13 and VWF as potential biomarkers for sorafenib response and prognosis in patients with HCC receiving sorafenib *** 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 *** 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 h

关键词： ADAMTS13 Von willebrand factor Biomarkers Hepatocellular carcinoma Sorafenib

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RFLPS ANALYSIS OF VON willebrand FACTOR GENE IN CHINESE POPULATION

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Chinese Science Bulletin 1992年第2期37卷 160-164页

作者：吴庆宇潘峻亮顾建明程大卫李佩霞阮长耿 Jiangsu Institute of Hematology Thrombosis and Hemostasis Research Lab Suzhou Medical College Suzhou 215007 PRC

Ⅰ. INTRODUCTION von willebrand factor (vWF), a large adhesive plasma glycoprotein, plays a central role in the adhesion of platelets to injured vessel wall and also serves as a carrier protein for coagulant factor Ⅷ (FⅧ), stabilizing the activity of FⅧ in plasma. The vWF gene of 178 kb in length is localized at chromosome 12p12-pter. The gene contains 52

关键词： von Willebraud factor(vWF) von willebrand disease(vWD) ristriction fragment length polymorphisms (RFLPs).

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Sma Ⅰ,Hha Ⅰ,Msp Ⅰ and Rsa Ⅰ restriction fragment length polymorphisms in the von willebrand factor gene of Chinese population

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Chinese Medical Journal 1998年第8期 14-17页

作者：李震宇王泳台虹万海英宋建新王迎春阮长耿

Abstract:Objective To study Sma Ⅰ, Hha Ⅰ, Msp Ⅰ and Rsa Ⅰ restriction fragment length polymorphisms in vWF gene of Chinese population. Methods The vWF gene from 52 unrelated individuals of Han Nationality, 44 of Yi tribe, 42 of Dai tribe was analyzed by polymerase chain reaction and digestion of the endonucleases of Sma Ⅰ, Hha Ⅰ, Msp Ⅰ and Rsa Ⅰ.Results The allele frequencies were 0.38∶ 0.62 for Sma Ⅰ+∶ Sma Ⅰ- and 0.38∶0.62 for Hha Ⅰ+∶ Hha Ⅰ-; 0.20∶ 0.80 for Msp Ⅰ+∶ Msp Ⅰ-; 0.93∶ 0.07 for Rsa Ⅰ+∶ Rsa Ⅰ- in Chinese Han population. The theoretical heterozygous rates were 0.46, 0.46, 0.36 and 0.13 of these polymorphisms, respectively. The allele frequencies were 0.43∶ 0.57 for Sma Ⅰ+∶ Sma Ⅰ- and 0.43∶0.57 for Hha Ⅰ+∶ Hha Ⅰ-, 0.26∶0.74 for Msp Ⅰ+∶ Msp- in Yi tribe and 0.36∶0.64 for Sma Ⅰ+∶ Sma Ⅰ- and Hha Ⅰ+∶ Hha Ⅰ-, 0.17∶ 0.83 for Msp Ⅰ+∶ Msp Ⅰ- in Dai tribe. The theoretical rates were 0.49 for Sma Ⅰ and Hha Ⅰ and 0.38 for Msp Ⅰ in Yi tribe; and 0.45 for Sma Ⅰ and Hha Ⅰ, 0.28 for Msp Ⅰ in Dai tribe, respectively.Conclusions The allele frequencies and theoretical rates of these polymorphisms in vWF gene are different between Chinese populations and Caucasians. They should be useful for the carrier detection and prenatal diagnosis in vWD families of Chinese.

关键词： willebrand Msp Rsa Sma Chinese factor fragment gene in Hha

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固相基质表面von willebrand Factor抗体的固定化研究

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生物医学工程学杂志 2005年第5期22卷 971-974页

作者：高运华杨新林北京理工大学生命科学与技术学院

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... 详细信息

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。

关键词：丝素蛋白膜聚乳酸膜 vWf抗体固定化 willebrand 固定化技术 vWf抗体 Factor von 基质体外凝血时间血管性假血友病固相

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

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Open Journal of Gastroenterology 2015年第6期5卷 49-57页

作者： Hasan Sedeek Mahmoud Ali A. Ghweil Shamardan E. Bazeed Hanan M. Fayed Mona M. Abdel Meguid Department of Tropical Medicine and Gastroenterology Faculty of Medicine South Valley University Qena Egypt Department of Clinical Pathology Faculty of Medicine South Valley University Qena Egypt

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.

关键词： Von willebrand Factor Antigen Esophageal Varices Prediction

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

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Open Journal of Gastroenterology 2014年第4期4卷 152-158页

作者： Ali Abdelrahman Ghweil Usama Ahmed Arafa Ashraf Khodeary Ahmed N. Salem Clinical Pathology Sohag University Sohag Egypt Internal Medicine Sohag University Sohag Egypt Tropical Medicine and Gastroenterology South Valley University Qena Egypt

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

关键词： Esophageal Varices FVII von willebrand Factor

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Autoimmune Diseases and Acquired Von willebrand Disease in Two Cases of Progeria

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International Journal of Clinical Medicine 2014年第20期5卷 1269-1276页

作者： Monem Makki Alshok Department of Medicine College of Medicine University of Babylon Babylon Iraq

Ammar A., a 23-year-old male patient, who lives in Babylon, Haswa District, and his mother describes symptoms of growth retardation, skin changes, hair changes early graying and alopecia. These manifestation started early during his childhood period. There is canseguanity between the patient’s mother & father also one of the patient’s sister has similar illness and one male brother died few months following his birth. We admit the patient to hospital due acute pulmonary infection in Jan 2009, which is controlled after a course of antibiotic and after 5 months he develops generalised mucocuteneous bullous eruption which shows partial response to oral prednisolone 2 mg/Kg. The patient has normal IQ and he is in the secondary school and he has normal blood picture and the only abnormal biochemical abnormalities is mild hyperlipidemia Serum cholestrol of 5.8 mmol/L and Serum Triglyceride of 260 mg/dl. Ammar’s Sister Qawthar A., who has a similar phenotypic manifestations, presented skin vitiligo and hepatosplenomegaly associated with sever anemia and jaundice and her presentation suggestive of autoimmune haemolytic anemia improved following blood transfusion, corticosteroid and azothioprim. In February 2014 Ammer presented with multiple and diffuse cuteneous ecchymymosis with markedly prolonged PTT and slightly proloned bleeding time highly consistent with acquired Von willebrand’s disease. In conclusion premature aging is a predisposing factor for disturbed immunity and development of autoimmune diseases.

关键词： Progeria Autoimmune Diseases Pemphigus Autoimmune Hemolytic Anemia Acquired Von willebrand Disease

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Von willebrand因子分布的免疫组织化学研究

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解剖学报 1990年第S1期21卷 108-113,148页

作者：李奈林李进第一军医大学组胚教研室广州510515

本文用抗人von willebrand因子(vWF)单克隆抗体SZ-29,采用免疫金银法和ABC法,研究了vWF在血管、血小板的分布情况。结果显示,vWF分布于腹主动脉,脐动脉和脐静脉的内皮,内皮基膜区、内皮下层及中膜内区,且vWF特异染色以内皮、内皮基膜区... 详细信息

本文用抗人von willebrand因子(vWF)单克隆抗体SZ-29,采用免疫金银法和ABC法,研究了vWF在血管、血小板的分布情况。结果显示,vWF分布于腹主动脉,脐动脉和脐静脉的内皮,内皮基膜区、内皮下层及中膜内区,且vWF特异染色以内皮、内皮基膜区染色最深。免疫金银法显示大部分血小板vwF特异银染呈颗粒状分布,约3—5％血小板整体胞体呈现银染。而免疫电镜观察,静止型血小板vWF分布于α-颗粒内,血小板膜没有或极少结合的vwF;激活型血小板,除α-颗粒外,vWF结合于血小板膜及开放管道系统膜上,在血小板伪足,尤其是伪足末端,常呈现vWF特异染色。

关键词： von willebrand 因子(vWF) 内皮内皮下层血小板免疫金银法 ABC 法

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Acquired von willebrand Syndrome in a Male with Systemic Lupus Erythematosus Presented with Mucocutaneous Bleeding and Treated with rFVIIa

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International Journal of Clinical Medicine 2014年第1期5卷 23-27页

作者： Maryam Hami Hassan Ahmadnia Zahra Rezaieyazdi Hassan Mansouritorghabeh Allergy Research Center Ghaem Hospital School of Medicine Mashhad University of Medical Sciences Mashhad Iran Endoscopic & Minimally Invasive Surgery Research Center Ghaem Hospital School of Medicine Mashhad University of Medical Sciences Mashhad Iran Kidney Transplantation Complications Research Center Department of Internal Medicine Ghaem Hospital School of Medicine Mashhad Uni-versity of Medical Sciences Mashhad Iran Rheumatic Disease Research Center Ghaem Hospital School of Medicine Mashhad University of Medical Sciences Mashhad Iran

Background: Systemic lupus erythematosis (SLE) is a disorder with multiple organ involvement. Haematological abnormalities have been addressed in it, but acquired von willebrand syndrome is a rarer phenomenon in current disease. The Case: We report acquired von willebrand syndrome and SLE in a man with brown rash on face, gingival bleeding, easy bruising and epistaxis and laboratory finding of decreased complement, high level of anti-nuclear antibody and anti-DNA. These findings confirmed the diagnosis of SLE. He underwent kidney biopsy and experienced severe pain at the site of biopsy, but the ultra-sonography evaluation showed small sub capsular haematoma at the site of biopsy. During the next 48 hours, gradually APTT prolongation was continued and haematocrit dropped. In spite of FFP infusion and taking tranexamic acid every eight hours, there wasn’t any improvement in haemostatic condition. He received Methylprednisolone and Cyclophosphamid pulses. The patient underwent surgery to roll out vascular complication, but there wasn’t any vascular problem. On the third day, recombinant activated factor VII was infused every two hours until oozing was stopped.

关键词： Acquired von willebrand Disease Lupus Erythematosus Systemic rFVIIa Bleeding

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

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World Journal of Gastroenterology 2016年第19期22卷 4786-4788页

作者： Georgios N Kalambokis Gerasimos Baltayiannis Dimitrios Christodoulou 1^(st) Division of Internal Medicine Medical School University of Ioannina 45110 Ioannina Greece Division of Gastroenterology Medical School University of Ioannina 45110 Ioannina Greece

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.

关键词： von willebrand factor antigen Endothelial dysfunction Treatment Portal hypertension

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