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.

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

Correlations of inhaled NO with the cTnI levels and the plasma clotting factor in rabbits with acute massive pulmonary embolism

Abstract Purpose: To investigate the correlation of inhaled nitric oxide (NO) on plasma levels of cardiac troponin I (cTnI) and von Willebrand factor (vWF), glycoprotein (GP) IIb/IIIa, granule membrane protein 140 (GMP-140) in rabbits with acute massive pulmonary embolism (PE). Methods: Thirty apanese white rabbits were divided into 3 groups, thrombus were injected in model group (n = 10), NO were inhalated for 24 h after massive PE in NO group (n = 10), saline were injected in control group (n = 10). The concentrations of vWF, GP IIb/IIIa, GMP-140 and cTnI were tested at 4, 8, 12, 16, 20, and 24 h, Correlation analyses were conducted between cTnI and vWF, GP IIb/IIIa, and GMP-140 by Pearson's correlation. Results: The concentration of cTnI and vWF, GP IIb/IIIa, and GMP-140 was increased in the model group, compared to control group. In the inhaled group, the concentrations of cTnI, vWF, GP IIb/IIIa, and GMP-140 were reduced compared to model group. There was a positive correlation between cTnI and vWF, GP IIb/IIIa, and GMP-140. Conclusion: Inhaled nitric oxide can lead to a decrease in levels of cardiac troponin I, von Willebrand factor, glycoprotein, and granule membrane protein 140, after an established myocardial damage, provoked by acute massive pulmonary embolism.

Evaluation of von Willebrand factor in COPD patients / Avaliação do fator de von Willebrand em pacientes com DPOC

OBJECTIVE: To compare the absolute serum von Willebrand factor (vWF) levels and relative serum vWF activity in patients with clinically stable COPD, smokers without airway obstruction, and healthy never-smokers. METHODS: The study included 57 subjects, in three groups: COPD (n = 36); smoker (n = 12); and control (n = 9). During the selection phase, all participants underwent chest X-rays, spirometry, and blood testing. Absolute serum vWF levels and relative serum vWF activity were obtained by turbidimetry and ELISA, respectively. The modified Medical Research Council scale (cut-off score = 2) was used in order to classify COPD patients as symptomatic or mildly symptomatic/asymptomatic. RESULTS: Absolute vWF levels were significantly lower in the control group than in the smoker and COPD groups: 989 ± 436 pg/mL vs. 2,220 ± 746 pg/mL (p < 0.001) and 1,865 ± 592 pg/mL (p < 0.01). Relative serum vWF activity was significantly higher in the COPD group than in the smoker group (136.7 ± 46.0% vs. 92.8 ± 34.0%; p < 0.05), as well as being significantly higher in the symptomatic COPD subgroup than in the mildly symptomatic/asymptomatic COPD subgroup (154 ± 48% vs. 119 ± 8%; p < 0.05). In all three groups, there was a negative correlation between FEV1 (% of predicted) and relative serum vWF activity (r2 = −0.13; p = 0.009). CONCLUSIONS: Our results suggest that increases in vWF levels and activity contribute to the persistence of systemic inflammation, as well as increasing cardiovascular risk, in COPD patients. .

OBJETIVO: Comparar os níveis séricos absolutos e a atividade sérica em percentual do fator de von Willebrand (FvW) em pacientes com DPOC clinicamente estáveis, tabagistas sem obstrução das vias aéreas e em indivíduos saudáveis que nunca fumaram. MÉTODOS: Foram incluídos no estudo 57 indivíduos, em três grupos: DPOC (n = 36), tabagista (n = 12) e controle (n = 9). Todos os participantes realizaram radiografia do tórax, espirometria e exame de sangue durante a fase de seleção. Os níveis séricos absolutos e a atividade sérica em percentual do FvW foram obtidos por turbidimetria e ELISA, respectivamente. A escala Medical Research Council modificada foi utilizada para classificar pacientes como sintomáticos ou assintomáticos/pouco sintomáticos no grupo DPOC (ponto de corte = 2). RESULTADOS: Os níveis absolutos do FvW no grupo controle foram significativamente menores que os nos grupos tabagista e DPOC: 989 ± 436 pg/mL vs. 2.220 ± 746 pg/mL (p < 0,001) e 1.865 ± 592 pg/mL (p < 0,01). Os valores em percentual de atividade do FvW no grupo DPOC foram significativamente maiores que no grupo tabagista (136,7 ± 46,0% vs. 92,8 ± 34,0%; p < 0,05), assim como foram significativamente maiores no subgrupo DPOC sintomático que no subgrupo DPOC assintomático/pouco sintomático (154 ± 48% vs. 119 ± 8%; p < 0,05). Houve uma correlação negativa entre o VEF1 (% do previsto) e os níveis em percentual de atividade do FvW nos três grupos (r2 = −0,13; p = 0,009). CONCLUSÕES: Nossos resultados sugerem que aumentos nos níveis de FvW e de sua atividade contribuem para a manutenção da inflamação sistêmica e o aumento do risco cardiovascular em pacientes com DPOC. .

Alteraciones de la hemostasia en el síndrome drepanocítico / Hemostasis alterations in sickle cell syndrome

El síndrome drepanocítico (SD) comprende un grupo de anemias hemolíticas hereditarias de tipo multisistémico asociadas a la hemoglobina S. Los pacientes que padecen este síndrome tienen un mayor riesgo, en comparación con individuos sanos, de presentar accidentes cerebrovasculares, hipertensión pulmonar, necrosis avascular de articulaciones, síndrome torácico agudo y complicaciones durante el embarazo, asociados a un estado de hipercoagulabilidad inducido por alteraciones en los diferentes componentes de la hemostasia, que incluyen la activación del endotelio y de los sistemas plaquetario, de la coagulación y de la fibrinólisis. Esta revisión resume las alteraciones en la hemostasia reportadas en los pacientes con SD, en los cuales se ha demostrado: mayor interacción de células endoteliales con leucocitos, hematíes y plaquetas; aumento de la expresión de proteínas de adhesión, como el factor von Willebrand y sus multímeros de alto peso molecular; aumento de la adhesión y la agregación plaquetaria y de la expresión de proteínas en sus membranas. En el sistema de coagulación se ha detectado aumento en la expresión del factor tisular (FT) en micropartículas derivadas de diferentes células, aumento de marcadores de activación de este sistema, entre estos los fragmentos 1.2 de la protrombina y los complejos trombina-antitrombina y una disminución de las proteínas C y S que actúan como anti-coagulantes. Adicionalmente, se han encontrado aumentados los marcadores de activación del sistema fibrinolítico como los dímeros D y los complejos plasmina/antiplasmina. Todas estas manifestaciones favorecen la aparición de complicaciones trombóticas, implicadas en el deterioro de la calidad de vida de los pacientes. Se recomienda implementar en el diagnóstico y seguimiento de esta enfermedad, la determinación de variables del sistema hemostático, con el fin de identificar alteraciones en etapas tempranas y aplicar terapias que puedan prevenir complicaciones trombóticas.

Sickle cell syndrome (SCS) includes a group of congenital hemolytic anemias associated to the presence of hemoglobin S, which is characterized by acute pain episodes and progressive damage of different organs. Some patients with sickle cell syndrome have shown, when compared with healthy individuals, an increased risk of presenting stroke, pulmonary hypertension, avascular necrosis of joints, acute chest syndrome and pregnancy complications, associated to a hypercoagulable state induced by alterations in different components of hemostasis, such as changes that include activation of the endothelium, platelet activity, coagulation and fibrinolytic systems. This paper compiles hemostasis disorders, associated with thrombotic manifestations, reported until now in sickle cell syndrom. These patients have an increase in activation markers of the coagulation system, such as prothrombin fragment 1.2, thrombin-antithrombin complex, etc., depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system and increased tissue factor expression. Similarly, abnormal expression of glycoproteins and increased adhesion and platelet aggregation have been reported. All these alterations produce a hypercoagulable state, which induces, among other things, the appearance of thrombotic complications. In view of the importance of controlling the different complications that can occur in patients with sickle cell syndrome, we recommend the implementation, in diagnosis and monitoring studies, of the evaluation of the different components of the hemostatic system, identifying alterations at an early stage and applying effective treatments to prevent thrombotic complications.

Tumor-Infiltrating Macrophage and Microvessel Density in Oral Squamous Cell Carcinoma

Tumor-associated macrophages (TAM) are the main cellular component in stroma of many tumors and participate in tumor angiogenesis. The aim of present study was to compare the microvascular density (MVD) and infiltrating macrophage density (IMD) in oral squamous cell carcinomas (OSCCs) with different histological grades. A histomorphometric analysis was performed after immunohistochemistry using antibodies such as von-Willebrand factor and CD68. A significant difference in MVD was found between well and moderately differentiated OSCCs (p<0.05). TAM were largely present in all studied tumors and the IMD was not different among OSCCs with different histological grades (p=0.381). Significant correlation between MVD and IMD was not observed (p=0.870). In conclusion, these results suggest that TAM and angiogenesis have an influence at different histological grades of OSCC. However, the lack of correlation between MVD and IMD could suggest that angiogenesis does not depend on the number of macrophages present in OSCC, but their predominant phenotype. Further studies involving distinct phenotypes of macrophages should be done to better understand the influence of TAM on the tumor angiogenesis.

Macrófagos associados a tumores (MAT) representam o componente principal do estroma de muitos tumores, além de participar da angiogênese tumoral. Este estudo comparou a microdensidade vascular (MDV) e densidade de macrófagos infiltrando o tumor (DMIT) em carcinoma escamocelular da boca (CEC) com diferentes graus histológicos de malignidade. Análise histomorfométrica foi empregada após técnica imuno-histoquímica para os anticorpos fator von-Willebrand e CD68. Uma diferença significante entre MDV e carcinomas bem e moderadamente diferenciados foi observada (p<0,05). MAT estavam fortemente presentes em todos os tumores estudados e a DMIT não foi diferente entre os diferentes graus histológicos de malignidade do CEC (p=0,381). Correlação significante entre MDV e DMIT não foi observada (p=0,870). Em conclusão, os resultados desse estudo sugerem a influência de MAT e angiogênese nos diferentes graus histológicos de malignidade do CEC. Entretanto, a ausência de correlação entre MDV e DMIT sugere que a angiogênese não depende do número de macrófagos presentes neste tipo de câncer, mas do fenótipo predominante. Outros estudos devem ser realizados a fim de contribuir para melhor compreensão da participação de MAT na angiogênese tumoral.

Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease

Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

Decreased plasma ADAMTS-13 activity as a predictor of postoperative bleeding in cyanotic congenital heart disease

OBJECTIVE: To analyze the preoperative plasma antigenic concentration and activity of von Willebrand factor and its main cleaving protease ADAMTS-13 in pediatric patients with cyanotic congenital heart disease undergoing surgical treatment and investigate possible correlations with postoperative bleeding. METHODS: Plasma antigenic concentrations (von Willebrand factor:Ag and ADAMTS-13:Ag) were measured using enzyme-linked immunoassays. Collagen-binding assays were developed to measure biological activities (von Willebrand factor:collagen binding and ADAMTS-13 activity). The multimeric structure of von Willebrand factor was analyzed using Western immunoblotting. Demographic, diagnostic, and general and specific laboratory data and surgery-related variables were subjected to univariate, bivariate, and multivariate analysis for the prediction of postoperative bleeding. RESULTS: Forty-eight patients were enrolled, with ages ranging from 9 months to 7.6 years (median 2.5 years). The plasma concentrations of von Willebrand factor:Ag and ADAMTS-13:Ag were decreased by 65 and 82%, respectively, in the patients compared with the controls (p<0.001). An increased density of low-molecular-weight fractions of von Willebrand factor, which are suggestive of proteolytic degradation (p = 0.0081), was associated with decreased ADAMTS-13 activity, which was likely due to ADAMTS-13 consumption (71% of controls, p = 0.0029) and decreased von Willebrand factor:collagen binding (76% of controls, p = 0.0004). Significant postoperative bleeding occurred in 13 patients. The preoperative ADAMTS-13 activity of <64.6% (mean level for the group), preoperative activated partial thromboplastin time, and the need for cardiopulmonary bypass were characterized as independent risk factors for postoperative bleeding, with respective hazard ratios of 22.35 (95% CI 1.69 to 294.79), 1.096 (95% CI 1.016 to 1.183), and 37.43 (95% ...

Engraftment of human adipose derived stem cells delivered in a hyaluronic acid preparation in mice / Implante de células tronco do tecido adiposo humano numa preparação de ácido hialurônico em camundongos

PURPOSE: To evaluate the implant of human adipose derived stem cells (ADSC) delivered in hyaluronic acid gel (HA), injected in the subcutaneous of athymic mice. METHODS: Control implants -HA plus culture media was injected in the subcutaneous of the left sub scapular area of 12 athymic mice. ADSC implants: HA plus ADSC suspended in culture media was injected in the subcutaneous, at the contra lateral area, of the same animals. With eight weeks, animals were sacrificed and the recovered implants were processed for extraction of genomic DNA, and histological study by hematoxilin-eosin staining and immunufluorescence using anti human vimentin and anti von Willebrand factor antibodies. RESULTS: Controls: Not visualized at the injection site. An amorphous substance was observed in hematoxilin-eosin stained sections. Human vimentin and anti von Willebrand factor were not detected. No human DNA was detected. ADSC implants - A plug was visible at the site of injection. Fusiform cells were observed in sections stained by hematoxilin- eosin and both human vimentin and anti von Willebrand factor were detected by immunofluorescence. The presence of human DNA was confirmed. CONCLUSION: The delivery of human adipose derived stem cells in preparations of hyaluronic acid assured cells engraftment at the site of injection.

OBJETIVO: Avaliar o implante de células tronco do tecido adiposo humano (CTTAH) em gel de ácido hialurônico (AH), injetados no tecido subcutâneo de camundongos atímicos. MÉTODOS: Implantes controle - HA com meio de cultura foram injetados no tecido subcutâneo da região infraescapular esquerda de 12 camundongos atímicos. Implantes de CTTAH: HA com CTTAH suspensas em meio de cultura foi injetado no subcutâneo da região contra lateral, dos mesmos animais. Com oito semanas, os animais foram sacrificados e os implantes recuperados foram processados para extração de DNA genômico, estudo histológico por coloração por hematoxilina eosina e imnuoflurescência utilizando anticorpos anti vimentina humana e anti fator de von Willebrand. RESULTADOS: Controles - implantes não visualizados no local da injeção. Uma substância amorfa foi observada nos cortes corados por hematoxilina eosina. Vimentina humana e fator anti von Willebrand não foram identificados. DNA humano não foi detectado. Implantes de CTTAH - Uma massa era visível no local da injeção. Células fusiformes foram observadas nos corte corados com hematoxilina eosina. Tanto vimentina humana quanto fator de von Willebrand foram identificados pela imunofluorescência. A presença de DNA humano foi confirmada. CONCLUSÃO: O implante de células tronco do tecido adiposo humano em veículo de ácido hialurônico gel assegurou a manutenção das células no local do implante.

A nodular growth on maxillary gingiva.

A case of angiosarcoma of maxilla is presented. The occurrence of angiosarcoma in the oral cavity is a rare incidence and maxilla is one of the rarest sites to be involved. The purpose of this article is also to emphasize the fact that sometimes small, innocent-looking masses in the oral cavity might actually turn out to be a highly destructive malignant tumor. Hence, a complete radiographic and histopathologic examination is mandatory.

Haemostatic activation in acute coronary syndrome patients in relation to physical exercise

Thrombosis is regarded to be a key factor in the development of acute coronary syndromes in patients with coronary artery disease [CAD], Platelets are known to play a fundamental role in acute coronary syndromes [ACS]. After atherosclerotic plaque rupture, platelets can form pathogenic, occlusive thrombi leading to acute ischemic events. The precise mechanisms of platelet activation in acute coronary syndromes are still under investigation. Physical activity could regulate the development of ACS via effects on platelet function. Several studies have shown that acute physical exercise increases platelet reactivity, typically assessed by aggregation assays, in both healthy individuals and in patients with cardiovascular disease. The aim of this study was to investigated the effect of moderate and strenuous exercise on arterial thrombus formation. Assay of some hemostatic marker as Platelet activation, thrombin generation [TF[pg/ml],TAT_ micro g/l and dimerand tPA concentration] von Willebrand factor, platelet aggregation tests, Coronary Angiography. haemostatic parameters in patients with ACS correlated with other clinical parameters under physical exercise Patients with ACS showed higher values for fibrinogen, tPA, TAT_, as indicators for a thrombin synthesis, and a marker for prothrombotic conditions, was elevated in patients with ACS,. Von Willebrand factor and D-dimer showed no statistical significant differences during rest., Exercise increased hemostatic parameters in an strenuous physical exercise in ACS Patients[< 0.05]. Exercise also increased plasma levels of fibrinogen and von Willebrand factor ,but there was an increase in the generation of T-AT complexes,. [P < 0.05]. Exercise did not affect platelet aggregation regardless of its intensity when triggered by the agonists ADP or collagen. Strenuous but not moderate exercise increases the thrombotic tendency in healthy sedentary male volunteers

Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease

Biomarkers have been identified for pulmonary arterial hypertension, but are less well defined for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH). We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and tested for associations with survival. A cohort of 46 inoperable CHDPAH patients (age 15.0 to 60.2 years, median 33.5 years, female:male 29:17) was prospectively followed for 0.7 to 4.0 years (median 3.6 years). Plasma levels of von Willebrand factor antigen (VWF:Ag), tissue plasminogen activator (t-PA) and its inhibitor (PAI-1), P-selectin, reactive C-protein, tumor necrosis factor alpha, and interleukin-6 and -10 were measured at baseline, and at 30, 90, and 180 days in all subjects. Levels of six of the eight proteins were significantly increased in patients versus controls (13 to 106 percent increase, P < 0.003). Interleukin-10 level was 2.06 times normal (P = 0.0003; Th2 cytokine response). Increased levels of four proteins (t-PA, PAI-1, P-selectin, and interleukin-6) correlated with disease severity indices (P < 0.05). Seven patients died during follow-up. An average VWF:Ag (mean of four determinations) above the level corresponding to the 95th percentile of controls (139 U/dL) was independently associated with a high risk of death (hazard ratio = 6.56, 95 percentCI = 1.46 to 29.4, P = 0.014). Thus, in CHDPAH, microvascular dysfunction appears to involve Th2 inflammatory response. Of the biomarkers studied, plasma vWF:Ag was independently associated with survival.

Transplantation of muscle-derived stem cells plus biodegradable fibrin glue restores the urethral sphincter in a pudendal nerve-transected rat model

We investigated whether fibrin glue (FG) could promote urethral sphincter restoration in muscle-derived stem cell (MDSC)-based injection therapies in a pudendal nerve-transected (PNT) rat, which was used as a stress urinary incontinence (SUI) model. MDSCs were purified from the gastrocnemius muscles of 4-week-old inbred female SPF Wistar rats and labeled with green fluorescent protein. Animals were divided into five groups (N = 15): sham (S), PNT (D), PNT+FG injection (F), PNT+MDSC injection (M), and PNT+MDSC+FG injection (FM). Each group was subdivided into 1- and 4-week groups. One and 4 weeks after injection into the proximal urethra, leak point pressure (LPP) was measured to assess urethral resistance function. Histology and immunohistochemistry were performed 4 weeks after injection. LPP was increased significantly in FM and M animals after implantation compared to group D (P < 0.01), but was not different from group S. LPP was slightly higher in the FM group than in the M group but there was no significant difference between them at different times. Histological and immunohistochemical examination demonstrated increased numbers of surviving MDSCs (109 ± 19 vs 82 ± 11/hpf, P = 0.026), increased muscle/collagen ratio (0.40 ± 0.02 vs 0.34 ± 0.02, P = 0.044), as well as increased microvessel density (16.9 ± 0.6 vs 14.1 ± 0.4/hpf, P = 0.001) at the injection sites in FM compared to M animals. Fibrin glue may potentially improve the action of transplanted MDSCs to restore the histology and function of the urethral sphincter in a SUI rat model. Injection of MDSCs with fibrin glue may provide a novel cellular therapy method for SUI.

Management of a pregnant patient at term with Von Willebrand disease - III

Von Willebrand disease [VWD] is a common inherited bleeding disorder involving a deficiency or abnormal function of a blood clotting protein called Von Willebrand factor [VWF]. Women with VWD require monitoring during and after pregnancy. This case report describe management of a patient presenting with type III VWD at term and during labour. She had history of severe post-partum haemorrhage [PPH] after cesarean section in previous pregnancy and again had a risk of life-threatening PPH in the current gestation which was managed by appropriate planning and timely decision

Alteraciones hemostáticas en pacientes con sangrado uterino anormal / Hemostatic alterations in patients with abnormal uterine bleeding

Conocer la frecuencia de defectos hemostáticos en mujeres con sangrado uterino anormal. Se estudiaron 55 mujeres de edades comprendidas entre 17 y 55 años, que presentaban sangrado uterino anormal. En cada paciente se realizó un estudio que comprendió: Historia clínica, examen físico (incluido examen ginecológico), biopsia endometrial, ultrasonograma transvaginal y pélvico y estudio hemostático a través de la determinación de los tiempos de protrombina y de tromboplastina parcial, concentraciones de factor VIII (FVIII), factor von Willebrand (FvW) y IX y agregación plaquetaria con epinefrina, ADP, colágeno y ristocetina. Hospital Nuestra Señora de Chiquinquirá, e Instituto de Investigaciones Clínicas “Dr. Américo Negrette”, Facultad de Medicina. Universidad del Zulia, Maracaibo, Venezuela. En todas las mujeres se halló una alteración orgánica, funcional o mixta en el área genital. Los tiempos de coagulación y las concentraciones de los factores estudiados fueron normales con excepción de una paciente cuya concentración de FVIII fue de 0,47U/μL. La agregación plaquetaria mostró alteraciones en el 51,1 por ciento de los casos. La frecuencia de alteraciones de la coagulación en mujeres con sangrado uterino anormal, fue similar a la de la población general, por esta razón no se justifica que todas las pacientes con sangrado uterino anormal, se sometan a un estudio de coagulación; sin embargo, la alta frecuencia de agregación plaquetaria anormal, se debe tomar en cuenta antes de decidir una conducta quirúrgica.

Câncer de mama e disfunção endotelial: [revisão] / Breast cancer and endothelial dysfunction: [review]

Entre as mulheres brasileiras a principal causa de mortalidade são as doenças cardiovasculares, seguida em freqüência pelo câncer, sendo o de mama o mais comum. É bastante conhecida a associação de câncer com eventos tromboembólicos, mas pouco estabelecida sua relação com os demais eventos cardiovasculares. Para estudar estes eventos desde suas alterações primordiais, como a lesão e disfunção endotelial e a formação da placa aterosclerótica, vários métodos têm sido utilizados. Dentre eles, a dosagem sérica de P e E-selectina e do fator de von Willebrand são relevantes devido à associação tanto com o risco cardiovascular quanto com o processo de progressão e formação de metástase do câncer de mama. Outro método de avaliação da função endotelial é a medida da dilatação da artéria braquial mediada por fluxo, que cada vez mais ganha popularidade devido à sua natureza não-invasiva e a comprovação de sua associação com a disfunção endotelial e risco de eventos cardiovasculares. Buscamos, através desta revisão, condensar o que houve de mais relevante nestes últimos anos sobre a associação de câncer, em especial o de mama, com lesão endotelial e risco cardiovascular.

The main cause of death among Brazilian women is cardiovascular disease followed by cancer with breast cancer as the most incident. The relationship between cancer and thrombosis is well known, although its association with other cardiovascular events is poorly understood. In order to study these events from the earliest findings such as endothelial injury and dysfunction and the evolving atherosclerotic plaque, many methods are currently being used. Among these methods, E- and P-selectin and the von Willebrand factor have been associated, either with cardiovascular risk or with breast cancer growth and metastasis. Brachial artery flow-mediated dilatation is a tool available that emerged in the last decade due to its noninvasive nature and its clear association with endothelial dysfunction and cardiovascular risk. The aim of this revision is to bring the newest and most relevant updates about the association of breast cancer, endothelial injury and cardiovascular risk.

Rosuvastatin and vascular dysfunction markers in pulmonary arterial hypertension: a placebo-controlled study

We investigated whether chronic rosuvastatin administration could improve the abnormalities of the circulating levels of vascular dysfunction markers in pulmonary arterial hypertension (PAH). Sixty patients, aged 13 to 60 years, with idiopathic (N = 14) or congenital heart disease-associated PAH (N = 46) were equally but randomly assigned to rosuvastatin treatment (10 mg a day, orally) or placebo for 6 months in a blind fashion. Plasma levels of P-selectin, tissue-plasminogen activator and its inhibitor as well as von Willebrand factor antigen were measured by enzyme-linked immunoassay before and after 1, 3, and 6 months of treatment. Baseline levels of biomarkers were elevated (68, 16, 45 and 46 percent increase relative to controls, for P-selectin, von Willebrand factor antigen, tissue-plasminogen activator and its inhibitor, respectively; P < 0.001). P-selectin values at baseline, 1, 3, and 6 months were 39.9 ± 18.5, 37.6 ± 14.6, 34.8 ± 14.6, and 35.4 ± 13.9 ng/mL, respectively, for the rosuvastatin group and 45.7 ± 26.8, 48.0 ± 26.9, 48.1 ± 25.7, and 45.7 ± 25.6 ng/mL for the placebo group. The P-selectin level was lower in the rosuvastatin group compared with placebo throughout treatment (P = 0.037, general linear model). A trend was observed towards a decrease in tissue-plasminogen activator in the statin group (16 percent reduction, P = 0.094), with no significant changes in the other markers. Since P-selectin is crucial in inflammation and thrombosis, its reduction by rosuvastatin is potentially relevant in the pathophysiological scenario of PAH.

A Case of Type 2N von Willebrand Disease with Homozygous R816W Mutation of the VWF Gene in a Nepalese Woman / 대한진단검사의학회지

Type 2N von Willebrand disease (vWD) can be confused with hemophilia A due to decreased factor VIII levels and a bleeding tendency, and differential diagnosis is of importance for providing the optimal treatment and genetic counseling. For the accurate diagnosis of type 2N vWD, von Willebrand Factor (vWF) function tests, multimer assay and gene mutation analysis are needed. The patient was a 38-yr-old Nepalese woman with a history of bleeding manifestations from childhood, such as hemarthrosis, intramuscular hematoma, and menorrhagia. Family history revealed that her mother and elder brothers also had bleeding manifestations from childhood. When she had a laparotomy in 1991, she was diagnosed as hemophilia A with factor VIII level of 3.6% and was transfused with whole blood, factor VIII and cryoprecipitates. In June 2007, she was admitted to our hospital for further evaluation of bleeding tendency. Blood tests revealed normal CBC; bleeding time, 2 min; PT, 14.9 sec (11-14 sec); aPTT, 51.2 sec (24-38 sec); and factor VIII, 4.9% (50-150%). The prolonged aPTT was corrected by 1:1 mixing test to the levels of 106% and 84%, respectively, before and after 2 hr-incubation at 37degrees C. No abnormalities were found in the vWF antigen level (71.3%), ristocetin cofactor assay (130.4%), and multimer assay. Direct DNA sequencing of the VWF gene revealed homozygous missense mutation located in exon 19, c.2446C>T (p.Arg816Trp), confirming the diagnosis of type 2N vWD.

Multimeric analysis in diagnosis of vWD variants in Indians.

von Willebrand disease is a common inherited bleeding disorder and the problem is undefined in developing countries due to limitation of its diagnostic facilities. The aim of the study was to diagnose vWD in patients with history of muco - cutaneous bleeding and characterization into its variants by multimeric analysis. 224 patients presenting with history of muco - cutaneous bleeding were selected. In all patients, platelet count, BT, PT, APTT, PF3 availability, clot solubility and factor VIII assay were done. Diagnosis of vWD was confirmed by RIPA, vWF: Ag, and vWF: RCo and its sub-characterization was done by multimeric analysis. 64 patients were diagnosed to have vWD. Of these, 21.9% were of type 1 vWD, 43.7% type 2 vWD, 1.6% acquired vWD and 32.8% type 3 vWD. By multimeric analysis, 2 patients had supranormal HMW multimers and two patients had normal distribution of vWF multimers were diagnosed as type 2M 'Vicenza'; and type 2M vWD respectively. It is concluded, that vWD is not an uncommon condition amongst Indian population.