Application Value of Plasma vWF and ADAMTS-13 in Evaluating Postoprative Vascular Endothelial Injury and Prognosis in Children with VSD / 中国实验血液学杂志

OBJECTIVE@#To dynamically observe the levels and activities of von Willebrand factor (vWF) and ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in plasma of children with congenital ventricular septal defect (VSD) during perioperative period, and explore the value of plasma vWF antigen (vWF:Ag) and ADAMTS-13 activity (ADAMTS-13: AC) in evaluating vascular endothelial injury and prognosis in children with VSD.@*METHODS@#In this cross-sectional study, a total of 74 children with VSD who underwent surgical treatment in TEDA International Cardiovascular Hospital from September 2018 to March 2019 were enrolled in the observation group. Among them, there were 28 cases of pure VSD, 32 cases of VSD combined with pulmonary hypertension, and 14 cases of VSD combined with valvular heart disease. 31 healthy children who underwent physical examination in Tianjin Children's Hospital during the same period were collected as the control group. The biochemical indexes of the children at admission were recorded. Peripheral plasma was collected at admission, postsurgery day 0 and day 1, respectively, and the levels of vWF activity (vWF:AC), vWF:Ag, ADAMTS-13 antigen (ADAMTS-13:Ag) and ADAMTS-13:AC were detected.@*RESULTS@#The level of plasma vWF:Ag and vWF:AC in the observation group before surgery were significantly lower than those in the control group (P<0.001), and increased continuously, on postsurgery day 0 and day 1 (P<0.001). The level of ADAMTS-13:Ag in the observation group before surgery was significantly higher than that in the control group (P<0.001), which decreased significantly on postsurgery day 0 (P<0.001), and increased significantly on postsurgery day 1 compared with postsurgery day 0 (P=0.033). The level of ADAMTS-13:AC in the observation group before surgery was significantly lower than that in the control group (P=0.015), which decreased significantly on postsurgery day 0 (P=0.037), and increased on postsurgery day 1, but the difference was not statistically significant (P=0.051). The changes of vWF and ADAMTS-13 in the three subgroups were basically similar to the observation group. vWF: Ag/ADAMTS-13: AC ratio on postsurgery day 0 and day 1 had high diagnostic value in vascular endothelial injury (AUC=0.80, P<0.001; AUC=0.93, P<0.001). Preoperative vWF and ADAMTS-13 levels, and related baseline indicators were not correlated with postoperative infection, bleeding, thrombosis,etc.@*CONCLUSION@#Preoperative vWF: Ag, vWF: AC and ADAMTS-13: AC levels in children with VSD are low, while the level of ADAMTS-13: Ag is high. After surgery, the levels of vWF: Ag and vWF: AC are increased and the level of ADAMTS-13: Ag is decreased. The postoperative vWF: Ag/ADAMTS-13: AC ratio shows high diagnostic value in evaluating vascular endothelial injury. There is no correlation between preoperative vWF and ADAMTS-13 levels with perioperative clinical events.

Disseminated intravascular coagulation phenotype is regulated by the TRPM7 channel during sepsis

BACKGROUND: Sepsis is an uncontrolled inflammatory response against a systemic infection that results in elevated mortality, mainly induced by bacterial products known as endotoxins, producing endotoxemia. Disseminated intravascular coagulation (DIC) is frequently observed in septic patients and is associated with organ failure and death. Sepsis activates endothelial cells (ECs), promoting a prothrombotic phenotype contributing to DIC. Ion channel mediated calcium permeability participates in coagulation. The transient reception potential melastatin 7 (TRPM7) non-selective divalent cation channel that also contains an α-kinase domain, which is permeable to divalent cations including Ca2+, regulates endotoxin-stimulated calcium permeability in ECs and is associated with increased mortality in septic patients. However, whether endothelial TRPM7 mediates endotoxemia-induced coagulation is not known. Therefore, our aim was to examine if TRPM7 mediates coagulation during endotoxemia. RESULTS: The results showed that TRPM7 regulated endotoxin-induced platelet and neutrophil adhesion to ECs, dependent on the TRPM7 ion channel activity and by the α-kinase function. Endotoxic animals showed that TRPM7 mediated neutrophil rolling on blood vessels and intravascular coagulation. TRPM7 mediated the increased expression of the adhesion proteins, von Willebrand factor (vWF), intercellular adhesion molecule 1 (ICAM-1), and P-selectin, which were also mediated by the TRPM7 α-kinase function. Notably, endotoxin-induced expression of vWF, ICAM-1 and P-selectin were required for endotoxin-induced platelet and neutrophil adhesion to ECs. Endotoxemic rats showed increased endothelial TRPM7 expression associated with a procoagulant phenotype, liver and kidney dysfunction, increased death events and an increased relative risk of death. Interestingly, circulating ECs (CECs) from septic shock patients (SSPs) showed increased TRPM7 expression associated with increased DIC scores and decreased survival times. Additionally, SSPs with a high expression of TRPM7 in CECs showed increased mortality and relative risk of death. Notably, CECs from SSPs showed significant results from the AUROC analyses for predicting mortality in SSPs that were better than the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scores. CONCLUSIONS: Our study demonstrates that sepsis-induced DIC is mediated by TRPM7 in ECs. TRPM7 ion channel activity and α-kinase function are required by DIC-mediated sepsis-induced organ dysfunction and its expression are associated with increased mortality during sepsis. TRPM7 appears as a new prognostic biomarker to predict mortality associated to DIC in SSPs, and as a novel target for drug development against DIC during infectious inflammatory diseases.

Diagnóstico de la enfermedad de von Willebrand / Diagnosis of von Willebrand disease

La enfermedad de von Willebrand (EVW) es el trastorno hemorrágico hereditario más común, y se caracteriza por presentar disminución de la capacidad del factor von Willebrand (FVW) de unirse a las plaquetas y al colágeno de la matriz extracelular durante la hemostasia primaria, debido a defectos cuantitativos o cualitativos. La EVW se clasifica en tres fenotipos principales: el 1 y el 3 que son trastornos cuantitativos, y el 2 que se subclasifica en 2A, 2B, 2M y 2N, y refleja los trastornos cualitativos. Para su diagnóstico son necesarios varios pasos: 1) la evaluación del historial de sangrado personal y familiar del paciente, 2) detección inicial de trastornos hemorrágicos, 3) pruebas para la detección de la EVW, 4) pruebas para la tipificación de la EVW, y 5) el análisis molecular. Tanto la subclasificación de la EVW como su diagnóstico continúan planteando desafíos importantes, motivo por el cual se realiza esta revisión, de manera que los profesionales de la salud tengan una guía que los oriente al momento de tener pacientes con algún trastorno hemorrágico que amerite descartar una EVW e implementar un tratamiento adecuado

von Willebrand disease (VWD) is the most common hereditary bleeding disorder, and is characterized by a decreased ability of the von Willebrand factor (VWF) to bind to platelets and extracellular matrix collagen during primary hemostasis, due to quantitative or qualitative defects. VWD is classified into three main phenotypes: 1 and 3, which are quantitative disorders, and 2 (2A, 2B, 2M and 2N) that reflects qualitative disorders. Several steps are necessary for its diagnosis: 1) evaluation of the patient's personal and family bleeding history, 2) initial screening tests for bleeding disorders, 3) tests for the detection of VWD, 4) tests for the classification of VWD, and 5) molecular analysis. Both the subclassification of VWD and its diagnosis continue to represent important challenges, which we aimed to describe in this review, so that health professionals have a guide to assist them when they have patients with a bleeding disorder that requires exclusion of VWD, and implementation of an appropriate treatment.

Antígeno del factor von Willebrand (FVW: Ag) / von Willebrand factor antigen (VWF: Ag)

Utilidad clínica de la prueba El factor von Willebrand (FVW) es una glicoproteína compuesta por multímeros con pesos moleculares que pueden variar desde 500 KDa hasta 20.000 kDa, que se sintetiza en las células endoteliales y en los megacariocitos, y se almacena en los cuerpos de Weibel-Palade y en los gránulos alfa de las plaquetas [1]. El papel del FVW en la hemostasia primaria es mediar la adhesión de las plaquetas a los componentes de la matriz extracelular, a través de los complejos glucoproteicos plaquetarios GPIbα y αIIb3ß; en la hemostasia secundaria, se asocia con el factor VIII para prevenir su degradación y favorecer la generación de trombina para la formación del trombo final

The clinical value of von Willebrand factor and VITRO score in evaluating disease progression in patients with HBV infection / 中华肝脏病杂志

Objective: To explore the clinical value of von Willebrand Factor (vWF) and VITRO score (vWF:Ag/platelet count) in assessing disease progression in patients with HBV infection. Methods: Randomly collect relevant clinical data of 308 patients with HBV infection (including 154 cases of chronic hepatitis B, 66 cases of hepatitis B cirrhosis in compensatory period, 88 cases of hepatitis B cirrhosis in decompensated period) from December 1, 2018 to January 5, 2021 in the Second Affiliated Hospital of Chongqing Medical University. The vWF values are measured by a uniform optical method, and all data are included using a uniform standard. Analyze the difference and significance of plasma vWF level and VITRO score in chronic hepatitis B, hepatitis B cirrhosis in the compensatory phase and decompensated phase. Results: The plasma vWF level and VITRO score of the chronic hepatitis B group were (139.47±76.44) and (0.86±0.8), respectively, and the hepatitis B cirrhosis compensated group was (164.95±67.12 and 1.44±1.14), respectively. Hepatitis cirrhosis decompensated group were (317.48±103.32 and 6.81±4.98), respectively; plasma vWF level and VITRO score increased with the progression of HBV infection, and the difference was statistically significant (F=133.669,P=0.000F=137.598,P=0.000).The plasma vWF level and VITRO score in patients with hepatitis B cirrhosis were (185.65±85.07 and 2.3±2.37) in the Child-Pugh A group, (304.74±105.81 and 6.37±5.19) in the B grade group, and (369.48±73.238.28±5.38) in the C grade group; plasma vWF level and VITRO score in patients with hepatitis B cirrhosis increased with the increase of Child-Pugh grade, and the difference was statistically significant (F=60.236, P=0.000F=32.854, P=0.000). The area under the curve (AUC) of plasma vWF level and VITRO score for diagnosing the decompensated stage of hepatitis B cirrhosis were 0.897 [95% confidence interval (CI): 0.855-0.940, P＜0.01], 0.949 [95% CI: 0.916-0.982, P＜0.01). When the vWF level and VITRO score were taken as cut-off values of 238.5% and 1.65, respectively, the sensitivity of diagnosing the decompensated stage of hepatitis B cirrhosis was 79.5% and 94.3%, the specificity was 92.3% and 87.7%, and the positive predictive value was 80.5% and 94.3%, the negative predictive value was 91.9% and 97.5%, and the diagnostic accuracy was 88.6% and 89.3%. Among the patients with decompensated hepatitis B cirrhosis, the level of vWF in the group with gastrointestinal bleeding (367.24±68.29)% was significantly higher than that in the group without gastrointestinal bleeding (286.15±109.69)%, and the difference was statistically significant (P＜0.001) The VITRO score of the group with gastrointestinal bleeding (9.12±5.4) was significantly higher than that of the group without gastrointestinal bleeding (5.36±4.13), and the difference was statistically significant (P＜0.01). The vWF level in the spontaneous peritonitis group was (341.73±87.92)% higher than that in the non-spontaneous peritonitis group (296.32±111.74)%, and the difference was statistically significant (P＜0.05). There was no statistical difference in VITRO score between the two groups. significance. Conclusion: Plasma vWF level and VITRO score can evaluate the progression of liver disease and the degree of decompensation of liver cirrhosis in patients with HBV infection, and have a predictive effect on various complications after decompensation of liver cirrhosis, and have certain guiding significance for early intervention measures.

Association between coagulation function and prognosis in patients with acute pancreatitis / 南方医科大学学报

OBJECTIVE@#To explore the correlation of coagulation function with the severity and prognosis of acute pancreatitis (AP) and identify the laboratory markers for early prediction and dynamic monitoring of the prognosis of AP.@*METHODS@#We retrospectively analyzed the clinical data of patients with AP admitted less than 72 h after onset to our hospital from December 1, 2017 to November 30, 2018. The correlation of coagulation function-related markers at admission and their changes during hospitalization with the prognosis of the patients was analyzed.@*RESULTS@#We screened the data of a total of 1260 patients with AP against the inclusion and exclusion criteria, and eventually 175 patients were enrolled in this analysis, among whom 52 patients had severe AP (SAP) and 12 patients died. Logistic regression analysis identified vWF: Ag, PT, PC, AT Ⅲ and D-dimer markers at admission as independent risk factors for predicting SAP and death. Dynamic monitoring of the changes in coagulation function-related markers in the disease course had greater predictive value of the patients' prognosis, and the indicators including vWF: Agmax, PTmax, APTTmax, TTmax, FIBmin, D-dimermax, PLTmin, PCmin, PLGmin, AT Ⅲmin, and their variations were all independent risk factors for predicting SAP and death. ROC analysis suggested that dynamic monitoring of the changes in the indicators, especially those of △vWF: Ag, △PT, △APTT, △FIB, △TT, △D-dimer, △PLT, △PC, △AT Ⅲ, △PLG, could effectively predict SAP and death in these patients (with AUC range of 0.63-0.84).@*CONCLUSION@#Patients with AP have vascular endothelial injuries and coagulation disorders. The markers including vWF: Ag, PT, PC, AT Ⅲ and D-dimer at admission are independent risk factors for predicting SAP and death, and dynamic monitoring of the changes in vWF: Ag、PT、APTT、TT、FIB、D-dimer、PLT、PC、AT Ⅲ and PLG can further increase the predictive value.

Research Advance in Treatment of Thrombotic Thrombocytopenic Purpura --Review / 中国实验血液学杂志

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, in which a severe deficiency of von Willebrand factor lyase results in thrombocytopenic clots that block blood vessels and eventually lead to terminal organ failure. Therapeutic plasma exchange is the cornerstone of TTP treatment which can greatly improves the survival rate of the patients. With the further exploration to the pathophysiological mechanism of TTP, other alternative therapies, new immunosuppressive agents, targeted antagonists, gene therapy and other emerging means gradually emerge, which are expected to further reduce the mortality and recurrence rate of the patients. In this review, the new developments in TTP treatment were summarized briefly.

Proteomics of serum exosomes in children in the acute stage of Kawasaki disease: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To study the biological processes and functions of serum exosomes in children in the acute stage of Kawasaki disease (KD), so as to provide new biomarkers for the early diagnosis of KD.@*METHODS@#In this prospective study, 13 children with KD who were treated in Children's Hospital of Soochow University from June 2019 to August 2020 were enrolled as the KD group, and 13 children who were hospitalized due to bacterial infection during the same period were enrolled as the control group. Whole blood was collected on the next morning after admission, serum samples were obtained by centrifugation, and exosomes were extracted through ultracentrifugation. Serum exosomes were analyzed by label-free quantitative proteomics, and differentially expressed proteins (DEPs) were screened out for functional enrichment analysis. A protein-protein interaction (PPI) network was plotted, and unique proteins were validated by targeted proteomics.@*RESULTS@#A total of 131 DEPs were screened out for the two groups, among which 27 proteins were detected in both groups. There were 48 unique DEPs in the KD group, among which 23 were upregulated and 25 were downregulated, and these proteins acted on "complement and coagulation cascades" and "the MAPK signaling pathway". Validation by targeted proteomics showed that FGG, SERPING1, C1R, C1QA, IGHG4, and C1QC proteins were quantifiable in the KD group. A total of 29 proteins were only expressed in the control group, among which 12 were upregulated and 17 were downregulated. Four proteins were quantifiable based on targeted proteomics, i.e., VWF, ECM1, F13A1, and TTR. A PPI network was plotted for each group. In the KD group, FGG and C1QC had close interaction with other proteins, while in the control group, VWF had close interaction with other proteins.@*CONCLUSIONS@#The serum exosomes FGG and C1QC in children in the acute stage of KD are expected to become the biomarkers for the early diagnosis of KD. For children with unexplained fever, detection of FGG, C1QC1, and VWF may help with etiological screening.

Advance in the diagnosis and treatment of hereditary thrombotic thrombocytopenic purpura / 中华医学遗传学杂志

Congenital thrombotic thrombocytopenic purpura, also known as Upshaw-Schulman syndrome, is a rare autosomal recessive genetic disorder. The main pathogenesis is homozygous or compound heterozygous variants of von Willebrand factor lyase (ADAMTS13) gene mapped to chromosome 9q34, which may result in severe lack of ADAMTS13 which cleaves von Willebrand factor (vWF) multimers in the plasma and increase the risk of microvascular thrombosis, leading to various complications. The advance of research on the pathogenesis of cTTP, recombinant human ADAMTS13 and gene therapy have made breakthroughs which may lead to cure of cTTP. This article has provided a review for the latest progress made in the diagnosis and treatment of cTTP.

Effects of material interfaces on orientation and function of fibrinogen / 生物医学工程学杂志

Fibrinogen (Fg) in human plasma plays an important role in hemostasis, vascular repair and tissue integrity. The surface chemistry of extracellular matrix or biological materials affects the orientation and distribution of Fg, and changes the exposure of integrin binding sites, thereby affecting its adhesion function to platelets. Here, the quantity, morphology and side chain exposure of Fg adsorbed on hydrophilic, hydrophobic and avidin surfaces were measured by atomic force microscopy (AFM) and flow cytometry (FCM), then the rolling behavior of platelets on Fg was observed through a parallel plate flow chamber system. Our results show that the hydrophobic surface leads to a large amount of cross-linking and aggregation of Fg, while the hydrophilic surface reduces the adsorption and accumulation of Fg while causing the exposure and spreading of the α chain on Fg and further mediating the adhesion of platelets. Fg immobilized by avidin / biotin on hydrophilic surface can maintain the monomer state, avoid over exposure and stretching of α chain, and bind to the platelets activated by the A1 domain of von Willebrand factor instead of inactivated platelets. This study would be helpful for improving the blood compatibility of implant biomaterials and reasonable experimental design of coagulation

Biological Function of CysR Domain of ADAMTS13 / 中国实验血液学杂志

OBJECTIVE@#To investigate the biological function of Cysteine rich (CysR) domain of a disintegrin and metalloprotease with thrombospondin type 1 repeats-13 (ADAMTS13) on cleavage of von Willebrand factor (vWF) and provide experimental evidence for exploring the pathogenesis of thrombotic thrombocytopenic purpura (TTP).@*METHODS@#The six amino acids (EDGTLS) in ADAMTS13 CysR domain were point mutated one by one, and the mutant ADAMTS13 proteins were expressed and purified. The cleavage products of vWF polymer by wild-type or mutant ADAMTS13 under denaturing condition or shear stress were separated by 1% SeaKem HGT agarose gel and detected by Western blot.@*RESULTS@#The mutant ADAMTS13 plasmids (M1: Glu515Ala; M2: Asp516Ala; M3: Gly517Ala; M4: Thr518Ala; M5: Leu519Ala; M6: Ser520Ala) were successfully constructed and the proteins of wild-type and mutant ADAMTS13 were purified. Wild-type ADAMTS13 almost completely cleaved the vWF polymer under denaturing condition, while the cleavage activity of M1 mutant was significantly reduced in the same condition (P<0.01). The cleavage activity of M1 mutant of ADAMTS13 was also significantly reduced compared with that of the wild-type under shear stress (P<0.01). The activity of M1 mutant to cleave the FRETS-vWF73 was dramatically reduced compared with that of wild-type ADAMTS13. However, the binding ability of M1 mutant to vWF was similar with that of wild-type ADAMTS13.@*CONCLUSION@#The CysR domain of ADAMTS13 plays an important role in the digestion of vWF under denaturing condition and shear stress. The Glu515 amino acid residue might be an important site for substrate recognition.

Clinical analysis of 61 patients with thrombotic thrombocytopenic purpura / 北京大学学报(医学版)

OBJECTIVE@#To analyze and summarize the clinical features, diagnosis, treatment and prognosis of 61 patients with thrombotic thrombocytopenic purpura (TTP), so as to improve the ability of diagnosis and treatment.@*METHODS@#The clinical data of 61 TTP patients admitted to Peking University People's Hospital from January 2004 to March 2019 were retrospectively analyzed, and the clinical manifestations, blood routine, hemolysis indicators, and von Willebrand factor lyase (von Willebrand factor-cleaving protease, vWF-CP, also known as ADAMTS13) of these patients were observed. According to the outcome at the time of discharge, they were divided into survival group and death group, and the differences in clinical characteristics, neutrophil to lymphocyte ratio (NLR) and plasma exchange between the two groups were compared. The PLASMIC scores were calculated and compared with ADAMTS13 to determine the accuracy of the PLASMIC score in predicting ADAMTS13.@*RESULTS@#Among the 61 TTP patients, 22 were males and 39 were females, with an average age of (48±17) years. In the study, 48 cases had pentalogy, only 9 had triad, and the remaining 4 had no neuropsychiatric symptoms. Twenty-seven cases (44.3%) died and 34 cases (55.7%) survived. Among the 61 TTP patients, the platelet count was (12.9±9.5)×109/L, the hemoglobin (66.5±20.7) g/L, the percentage of erythrocyte fragments 3% (2%, 7%), and the plasma free hemoglobin increased to 360 (200, 457) mg /L, and the lactate dehydrogenase 1 508 (811, 2 133.8) U/L. The blood clotting was basically normal. The ADAMTS13 value of 30 patients was 49.0 (40.8, 61.3) μg/L, the ADAMTS activity of 10 patients was < 5%, and the remaining 21 patients were not checked. The PLASMIC score was 6-7 in 58 cases, 5 in 2 cases, and 4 in 1 case. The PLASMIC score predicted the decreased activity or the reduction of ADAMTS with a sensitivity as high as 97.5%. The NLR in the death group was higher than that in the survival group, but the difference was not statistically significant (P>0.05). The total amount and frequency of plasma exchange (PEX) in the death group were significantly less than those in the survival group, and the difference was statistically significant (P < 0.05). There was no significant difference in the treatment of glucocorticoids and human immunoglobulin between the two groups (P>0.05).@*CONCLUSION@#PEX can significantly improve the survival rate of TTP patients. PLASMIC score can easily and quickly predict the possibility of ADAMTS13 activity reduction, which is beneficial to the early diagnosis of TTP and PEX treatment. NLR can reflect the systemic inflammatory process, but its significance in TTP needs further study.

Nesiritide protects endothelial function after balloon-induced trauma in the iliac artery in rabbits

To assess the effect of nesiritide on the endothelial function of iliac arteries following endothelia trauma. Right iliac artery trauma was created with a balloon catheter. Ten rabbits were treated with a 4-week subcutaneous injection of nesiritide at a fixed daily dose of 0.1mg/kg. Ten rabbits received daily normal saline injection. Plasma endothelin 1 (ET-1), nitric oxide (NO), and Von Willebrand Factor (vWF) were measured before and after the therapies. Tissue proliferating cell nuclear antigen (PCNA) was measured after the treatment. After the treatment, in the therapeutic group, the area under internal elastic membrane and the residual lumen area were higher than in the normal saline group (P <0.05). The plasma levels of ET-1 (91.6±6.8 vs 114.9±6.3 ng/L, P =0.001), vWF (134.6±10.8% vs 188.8±10.4%, P =0.001) and the ratio of PCNA positive expression (11.7±4.2% vs 36.2±11.4%, P =0.005) in the therapeutic group was lower than in the normal saline group, while the plasma levels of NO was higher (89.7±9.3 vs 43.5±5.3 µmol/L, P =0.001). Nesiritide inhibited remodeling of rabbit iliac artery following endothelial trauma. The inhibition of vascular remodeling may be related to the alleviated endothelial dysfunction and reduced expression of tissue proliferating cell nuclear antigen

A Simple and Nonenzymatic Method to Isolate Human Corpus Cavernosum Endothelial Cells and Pericytes for the Study of Erectile Dysfunction

Grupos sanguíneos y su relación con los niveles plasmáticos del Factor de von Willebrand / Blood groups and their relationship with plasma levels of von Willebrand Factor

Resumen Introducción: El tipo de grupo sanguíneo entre otros factores, influye en los niveles plasmáticos del Factor de von Willebrand (FvW), su actividad biológica podría incidir en el desarrollo de eventos trombóticos y hemorrágicos. Objetivo: Describir las características y los mecanismos de reacciones postrasduccionales del grupo sanguíneo que permiten la variación en la concentración plasmática del FvW. Materiales y métodos: Revisión teórico descriptiva de tipo documental. Las bases de datos consultadas fueron Medline, Lilacs, ScienceDirect, Scopus, SciELO, Proquest, Ovid y Pubmed. Como criterio de selección se incluyeron artículos en idioma inglés y español a partir del año 2010 y algunos anteriores como referente histórico. Resultados: Se describieron los principales mecanismos e investigaciones que evidencian la influencia del tipo de grupo sanguíneo ABO en los niveles plasmáticos del FvW, así como la estructura y función de dicha proteína. Conclusiones: Las concentraciones plasmáticas del FvW pueden depender del tipo de grupo sanguíneo, la edad, sexo, embarazo, ciclo menstrual, variación de proteínas y factores bioquímicos e inmunológicos. Se podría tener en cuenta el tipo de grupo sanguíneo de los pacientes como un posible factor predictor a futuro de complicaciones clínicas tanto trombóticas como hemorrágicas.

Abstract Introduction: The type of blood group among other factors influences the plasma levels of von Willebrand Factor (FvW) and its biological activity could influence the development of thrombotic and hemorrhagic events. Objective: To describe the characteristics and mechanisms of post-translational reactions of the blood group that generate variation in the plasma concentration of FvW. Materials and methods: A descriptive theoretical review of documentary type. The databases consulted were Medline, Lilacs, ScienceDirect, Scopus, SciELO, Proquest, Ovid and Pubmed. As a selection criterion, articles in English and Spanish were included beginning in 2010 and some previous ones as historical reference. Results: The main mechanisms and investigations that show the influence of the ABO blood group type on the plasma levels of FvW, as well as the structure and function of this protein were described. Conclusions: FvW plasma concentrations may depend on the type of blood group, age, sex, pregnancy, menstrual cycle, protein variation and biochemical and immunological factors. The type of blood group of patients could be considered as a possible future predictor of both thrombotic and hemorrhagic clinical complications.

El papel de la enfermedad de von Willebrand en la hemorragia uterina anormal / Von Willebrand Disease in Abnormal Uterine Bleeding

RESUMEN La hemorragia uterina anormal es un término empleado para las alteraciones en la regularidad, duración y/o volumen de sangrado menstrual y es considerada una causa común de consulta médica y en ocasiones supone un reto diagnóstico para el médico tratante. Dentro del abordaje de la etiología de dicha patología, las coagulopatías afectan alrededor del 13 por ciento de las mujeres, y la más común es la enfermedad de von Willebrand. El objetivo de este trabajo fue realizar una revisión de la literatura científica actual sobre el papel que cumple la enfermedad de von Willebrand en la hemorragia uterina anormal. Esta es una patología hereditaria derivada de una deficiencia del factor von Willebrand encargado de la adhesión plaquetaria. La prevalencia de esta enfermedad puede ser baja, sin embargo, cuando se estudia la población de mujeres con menorragia, la frecuencia puede ir de 5 a 20 por ciento. Se han descrito diferentes problemas ginecológicos asociados a la enfermedad de von Willebrand, tales como menorragia, dismenorrea y una importante deficiencia de hierro asociada a esta, además de una mayor incidencia de quistes ováricos, endometriosis, hiperplasia endometrial y pólipos endometriales. La literatura actual sugiere que se realice tamizaje a aquellas mujeres con cuadro clínico sugestivo. Con respecto al tratamiento la literatura reporta el uso de ácido tranexámico y anticonceptivos orales, pero el que mayor utilidad ha demostrado es la desmopresina(AU)

ABSTRACT Abnormal uterine bleeding is a term used for alterations in the regularity, duration and / or volume of menstrual bleeding and it is considered a common cause of medical consultation; sometimes it is a diagnostic challenge for the treating physician. Within the aetiology approach of said pathology, coagulopathies affect around 13 percent of women, and the most common is von Willebrand disease. The objective is to review the current scientific literature on the influence of von Willebrand disease in abnormal uterine bleeding. This is an inherited pathology derived from a deficiency of the von Willebrand factor responsible for platelet adhesion. The prevalence of this disease may be low, however, when studying the population of women with menorrhagia, the frequency can range from 5 to 20 percent. Different gynecological problems associated with von Willebrand disease have been described, such as menorrhagia, dysmenorrhea and a significant iron deficiency associated with it, in addition to a higher incidence of ovarian cysts, endometriosis, endometrial hyperplasia and endometrial polyps. The current literature suggests that those women with suggestive clinical symptoms should be screened. Regarding treatment, the literature reports the use of tranexamic acid and oral contraceptives, nonetheless desmopressin has proven to be most useful(AU)

von Willebrand Factor Gene Expression in Primary Lower Grade Glioma: Mutually Co-Occurring Mutations in von Willebrand Factor, ATRX, and TP53

BACKGROUND: Venous thromboembolism is a common complication in patients with glioma. The clotting factor von Willebrand factor (VWF) is a highly adhesive procoagulant molecule that mediates platelet adhesion to endothelial and subendothelial surfaces. In the current analysis, we examined The Cancer Genome Atlas (TCGA) data to assess the VWF gene in patients with lower grade gliomas. METHODS: For newly diagnosed gliomas, we evaluated the association between VWF and overall survival in the Genomic Data Commons TCGA Lower Grade Glioma (LGG) dataset in TCGA. Simple statistics were calculated to identify patterns of mutual exclusivity or co-occurrence of VWF mutations. For each pair of query genes an odds ratio was calculated that indicates the likelihood that the mutations in the two genes are mutually exclusive or co-occurrent across the selected cases. To determine whether the identified relationship was significant for a gene pair, Fisher's exact test was performed. RESULTS: Lower grade gliomas with less VWF gene expression had significantly better survival than those with more VWF gene expression (hazard ratio 0.64, 95% confidence interval 0.44 to 0.92, p=0.015 log rank test). When we analyzed the data with Cox regression, VWF expression had a significant effect on survival (p=0.02) that was unrelated to the effect of IDH1 expression (p=0.062), TP53 expression (p=0.135), independent of ATRX expression (p=0.021) and histology (astrocytoma versus oligoastrocytoma and oligodendroglioma, p=0.002). VWF mutations significantly co-occur with mutations in TP53 and ATRX (p<0.001). CONCLUSION: The deleterious prognostic effect of VWF expression and its co-occurrent mutations with TP53 and ATRX in lower grade gliomas are not surprising, given VWF's role in other cancers. Therefore, VWF gene expression may be a clinically important risk marker in lower grade glioma.

Establishment of Flow Cytometric Immunobead Array for Detecting Plasma Von Willebrand Factor Activity and Its Clinical Application in the Prognosis of Ischemic Stroke / 中国实验血液学杂志

OBJECTIVE@#To establish a novel flow cytometric immunobead array (FCIA) for detecting plasma von Willebrand factor activity (vWF:GPIbR) and apply it in ischemic stroke (IS).@*METHODS@#Microspheres coated with anti-human platelet glycoprotein Ibα (GPIbα) monoclonal antibody SZ151 IgG, were incubated with recombinant fragment of GPIbα, then added ristocetin and plasma, finally incubated with FITC-conjugated sheep-anti-human vWF IgG polyclonal antibody, and detected by flow cytometry. vWF antigen (vWF:Ag), vWF:GPIbR, and vWF collagen binding assay (vWF:CB) were also included for evaluating vWF levels in IS patients.@*RESULTS@#The intra-assay coefficient variations (CVs) and inter-assay CVs of FCIA were 7.7% and 13.5%, respectively. The slope of the linear regression was 0.9739 (r=0.855, P<0.001), and the Bland-Altman bias was 9.95%, indicating a good correlation between FCIA and ELISA. The FCIA had better sensitivity, specificity and accuracy as compared with those by ELISA (P<0.05). The levels of vWF:Ag, vWF:GPIbR and vWF:CB in IS patients were significantly higher in comparison with those in healthy controls (H=7.8, 6.4, 6.2, respectively, P<0.01), the level of vWF:GPIbR in IS patients positively correlated with levels of vWF:Ag, high-sensitivity C-reactive protein, Autar score and hospitalization time.@*CONCLUSION@#The FCIA for detecting plasma vWF:GPIbR is more specific and accurate than ELISA. The vWF:GPIbR is involved in the paroxysm of IS, which could be used to evaluate the risk of thrombosis in IS patients.

Injury of rat blood vessels caused by acute ozone exposure and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the vascular damage effects and possible mechanism of acute exposure to ozone (O) in male Wistar rats.@*METHODS@#One hundred and twenty male Wistar rats were randomly divided into six groups, 20 in each group. The experimental animals were placed in a gas poisoning cabinet, the control group was exposed to filtered air, and the treatment group was exposed to ozone at concentrations of 0.12 ppm, 0.5 ppm, 1.0 ppm, 2.0 ppm, and 4.0 ppm, respectively, for 4 hours. Arterial blood pressure data were obtained by PC-lab medical physiological signal acquisition system. Blood rheology indicators and blood biochemical indicators were detected by Tianjin Dean Diagnostic Laboratory. Serum endothelin-1 (ET-1), homocysteine (HCY), von Willebrand factor (vWF), 8-hydroxydeoxyguanosine (8-OhdG), interleukin (IL-6) and tumor necrosis factor alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA) microplate assay. Oxidative stress indicators superoxide dismutase (SOD) activity and malondialdehyde (MDA) were determined by xanthine oxidase method, thiobarbituric acid (TBA) method, reduced glutathione (GSH) and nitric oxide (NO) were tested by using microplate colorimetry. Paraffin sections were prepared from thoracic aorta tissue, and vascular structure was observed by HE staining.@*RESULTS@#Acute exposure to 0.12 ppm ozone could cause a significant increase in arterial systolic blood pressure (SBP). Exposure to different concentrations of ozone could cause a significant increase in plasma viscosity, and the K value of the ESR equation was significantly increased in the 1.0 ppm ozone exposure group. Both the relative and reduced viscosities were significantly reduced at ozone concentrations of 0.5 ppm and 4.0 ppm, while the red blood cell deformation index was increased significantly at ozone concentrations of 0.12 ppm, 0.5 ppm, 1.0 ppm, and 2.0 ppm. Acute ozone exposure resulted in the decrease of total cholesterol content. The content of high-density lipoprotein cholesterol (HDL-C) was significantly reduced in the 0.12 ppm ozone exposure group. When the ozone concentration was higher than 1.0 ppm, the body may also had an inflammatory reaction (increased TNF-α) and oxidative stress (increased MDA, decreased GSH). Acute exposure to ozone could lead to elevated levels of ET-1 in the blood, with significant differences in the 4.0 ppm concentration group, while HCY levels were decreased firstly and then increased, reaching the highest in the 1.0 ppm concentration group. No obvious pathological changes were observed in the thoracic aorta.@*CONCLUSION@#Acute ozone exposure can affect arterial blood pressure, blood rheology and cholesterol metabolism in rats. The possible mechanism is that ozone exposure leads to inflammatory reaction and oxidative stress reaction, causing vascular endothelial function damage, and vascular endothelial cells increase with ozone exposure concentration.