Unique ELISA-Based Assays for VWF-GPIb Interactions and the Impact of Racial Differences on VWF Testing

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 423-423
Author(s):  
Veronica H. Flood ◽  
Patricia A. Morateck ◽  
Pamela A. Christopherson ◽  
Kenneth D. Friedman ◽  
Joan Cox Gill ◽  
...  
Keyword(s):  
Racial Differences ◽  
Von Willebrand Disease ◽  
Mutant Form ◽  
Plasma Samples ◽  
Healthy Donors ◽  
Significant Difference ◽  
The Mean ◽  
Clinical Biology ◽  
Von Willebrand ◽  
The Impact

Abstract Diagnosis of von Willebrand disease (VWD) relies primarily on assays of von Willebrand factor (VWF) function (VWF:RCo) and concentration of VWF protein (VWF:Ag). VWF:RCo is a surrogate measure of VWF activity for VWF interaction with the GPIb receptor on platelets. For VWD screening purposes, some have advocated that VWF:RCo is the most appropriate single test, but variability and reproducibility of VWF:RCo assays between laboratories has been problematic. Alternative assays have therefore been sought. Type 2 VWD variants, 2A, 2B, and 2M, are characterized by a discrepancy between the VWF:Ag and VWF:RCo, yet numerous factors can affect this ratio. Previously, our laboratory has reported a cell based assay to measure VWF interaction with the GPIb complex by flow cytometry, but such assay instrumentation is not available in hemostasis testing laboratories. Plasma samples were collected from 75 healthy donors enrolled in the TS Zimmerman Program for the Molecular and Clinical Biology of VWD, including 44 African American (AA) and 31 Caucasian subjects. VWF:Ag and VWF:RCo levels were performed in a central laboratory, as were collagen binding (VWF:CB) and propeptide (VWFpp) testing. Two ELISA-based assays were developed to measure VWF interaction with GPIb using recombinant GPIbα – one using normal GPIb with ristocetin (VWF:RCo ELISA) and the other a mutant form of GPIbα containing the platelet-type mutations D235Y and M239V that does not require ristocetin (VWF:IbCo ELISA). A monoclonal antibody is used to capture the rGPIb and to orient the GPIb for subsequent interaction with VWF. Serially diluted plasma samples were incubated for 1 hour with or without added ristocetin and monoclonal antibodies to VWF were used to detect the presence of VWF. Both assays utilized a 10 minute agitation at the end of the plasma incubation step. For all subjects, the mean VWF:Ag was 142, the mean VWF:RCo was 124, and the mean VWF:RCo/VWF:Ag ratio was 0.90. The two new assays yielded similar activity results when all the control subjects were analyzed, with a mean of 104 for the VWF:RCo ELISA and a mean of 108 for the VWF:IbCo ELISA. Both assays correlated well with each other and with the VWF:RCo. R squared values as determined by linear regression were 0.79 for the comparison of the VWF:RCo ELISA with the VWF:IbCo ELISA and 0.80 for comparison of either with the regular VWF:RCo. When the results were analyzed by race, however, a significant difference was seen for the two ristocetin-containing assays. The mean VWF:RCo/VWF:Ag ratio for the AA controls was 0.85, compared to 0.95 for the Caucasian controls (p<0.025). For the ristocetin ELISA, the mean was 0.54 for the AA controls and 0.79 for the Caucasian controls (p<0.001). However, no significant racial difference was seen for the VWF:IbCo ELISA with mean of 0.72 for the AA controls and 0.81 for the Caucasian controls (p=NS). Other VWF ratios have been proposed to be used to classify VWD – VWF:CB/VWF:Ag, FVIII/VWF:Ag, and VWFpp/VWF:Ag, but none were significantly different by race. The use of ELISA-based assays to determine VWF function is therefore feasible and may alleviate some of the problems inherent in the traditional VWF:RCo assay, including reproducibility and the technical demands of the assay. The VWF:IbCo assay may also eliminate racial differences in the VWF activity to antigen ratio, thus preventing the potential for erroneous diagnosis of VWD. Furthermore, the ELISA-based assays can be performed using standard hemostasis laboratory instrumentation.

Fourteen Percent of Healthy African Americans Participating In the Zimmerman Program for the Molecular and Clinical Biology of VWD (ZPMCB VWD) Are Heterozygous for the VWF Gene Mutation H817Q Associated with Type 2N Von Willebrand Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 239-239
Author(s):  
Kenneth D Friedman ◽  
Daniel B. Bellissimo ◽  
Pamela A. Christopherson ◽  
Veronica H Flood ◽  
Joan Cox Gill ◽  
...  
Keyword(s):  
African American ◽  
African Americans ◽  
Racial Differences ◽  
Healthy Subjects ◽  
Von Willebrand Disease ◽  
Compound Heterozygous ◽  
Healthy Controls ◽  
Clinical Biology ◽  
A1 Domain ◽  
Von Willebrand

Abstract Abstract 239 Von Willebrand disease (VWD) is a common hereditary bleeding disorder caused by reduced concentration or abnormal structure/function of von Willebrand Factor (VWF). Most published studies of normal VWF have been carried out in European or North American subjects without regard to racial differences. In the process of studying healthy controls in the Zimmerman Program for the Molecular and Clinical Biology of VWD (ZPMCB-VWD), we identified a common polymorphism (D1472H) in the VWF A1-domain in African Americans that affects the measurement of VWF function by ristocetin cofactor (VWF:RCo) but does not appear associated with increased bleeding risk. We therefore explored whether other polymorphisms or mutations were identified more frequently in African Americans. VWF sequencing was performed on 191 healthy controls including 66 that were self-identified as African American. European Bleeding Score was obtained and normal in all healthy subjects. Among the African Americans, 9 individuals were heterozygous for the reported type 2N H817Q mutation and one was homozygous. Factor VIII binding to VWF (VWF:F8B) was determined with a standard FVIII binding assay using the subject's plasma VWF and recombinant FVIII. The VWF:F8B was significantly reduced in H817Q heterozygotes when compared to 10 healthy study subjects without the H817Q mutation (65 ± 11 versus 108 ± 11, p=0.003). The VWF:F8B was further reduced to 37 using the plasma VWF from the homozygous H817Q subject. However, the observed VWF:F8B in these individuals with H817Q are still considerably higher that that observed in patients enrolled in ZPMCB-VWD that are either homozygous or compound heterozygous with the common R854Q type 2N VWD (VWF:F8B < 13). Of the 116 self-identified Caucasian healthy subjects, none had the H817Q mutation, but 3 were heterozygous for the R854Q mutation; their mean plasma VWF:F8B was reduced to 51. While the homozygous R854Q patients had reduced plasma FVIII levels (mean FVIII=24 IU/dL), none of the sequenced healthy control subjects had plasma FVIII levels below 53 IU/dL, Some have advocated FVIII/VWF:Ag ratios as a screen for type 2N VWD. The subject with homozygous H817Q had only a mildly reduced FVIII/VWF:Ag ratio (0.59), while the heterozygous H817Q were not reduced (mean=0.90), thereby demonstrating that the VWF:F8B assay has greater sensitivity for type 2N VWF binding defects than the FVIII/VWF:Ag ratio. Since the previously reported A1-domain D1472H polymorphism was common in African Americans, we explored the prevalence of this polymorphism in the healthy subjects with the H817Q mutation. All H817Q heterozygous subjects were either homozygous (4) or heterozygous (5) for the D1472H polymorphism. The one individual who was H817Q homozygous was also D1472H homozygous, suggesting that there may be an extended haplotype present in African Americans. In summary, an H817Q type 2N mutation is commonly found in healthy African American subjects with an allele frequency of 0.083, predicting that approximately 7 in 1,000 African Americans would be homozygous for the H817Q type 2N mutation. Our data, and the rarity of diagnosis of type 2N VWD in African Americans suggests that while mutation H817Q may interfere with the interaction of FVIII with VWF, this mutation appears to confer little or no clinical symptoms. Disclosures: No relevant conflicts of interest to declare.

Common VWF Haplotypes in Normal African-Americans and Caucasians Recruited into the ZPMCB-VWD and Their Impact on VWF Laboratory Testing.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 714-714
Author(s):  
Veronica H. Flood ◽  
B.C. Kautza ◽  
C.A. Miller ◽  
B.R. Branchford ◽  
J.C. Gill ◽  
...  
Keyword(s):  
African American ◽  
African Americans ◽  
Gene Sequencing ◽  
Von Willebrand Disease ◽  
Control Group ◽  
Healthy Controls ◽  
Significant Difference ◽  
The Mean ◽  
Bleeding Score ◽  
Von Willebrand

Abstract Von Willebrand disease (VWD) is a common bleeding disorder that has been reported to affect up to 1% of the population. Diagnostic testing for VWD relies on specific tests of von Willebrand factor (VWF) that include VWF antigen (Ag) and VWF ristocetin cofactor activity (RCo). Variability in these tests, especially in the RCo, has the potential to affect diagnosis of VWD. Clinically, the RCo/Ag ratio is used to identify patients with type 2M VWD, of which 35% of our local type 2M index cases were of African-American descent. As part of the ZPMCB-VWD, a large study of both healthy controls and patients with VWD, we evaluated VWF Ag, RCo, multimers, EU bleeding score, and VWF gene sequencing to look for mutations and/or common polymorphisms (SNPs) that might contribute to RCo measurement. Healthy controls completed a computerized version of the EU bleeding score and provided blood for clinical VWF testing. Since platelet VWF binding primarily involves the A1 domain of VWF, exon 28 gene sequencing was analyzed and common SNPs were identified, particularly in African-Americans (AA) with altered RCo/Ag ratios. Statistical comparisons were performed using t-tests. For the AA control group, the presence of specific exon 28 SNPs, including I1380V, N1435S, and D1472H, correlated with a low RCo/Ag. In controls, the 3 SNPs occurred together in 22% of AA and 1.5% of Caucasians. For AA controls with all 3 SNPs, the mean Ag was 155, RCo 115, and RCo/Ag 0.77, while for AA without the 3 SNPs, the mean Ag was 129, RCo 129, and RCo/Ag 1.01. The difference in RCo/Ag ratio was significant (p<0.001). In comparison, the Caucasian controls without the 3 SNPs had a mean Ag of 108, RCo of 115, and RCo/Ag of 1.08. When only D1472H was considered, a significant difference in RCo/Ag ratio was noted for both African-American and Caucasian controls with D1472H (present in 63% of AA and 24% of Caucasian controls). For AA controls with D1472H, the mean RCo/Ag ratio was 0.82 (range 0.42–1.16) compared to 1.01 for those without the SNP (p<0.001). The Caucasian controls with D1472H had a mean ratio of 0.87 (range 0.57–1.17) compared to 1.08 for those without the SNP (p<0.001). EU Bleeding Score was not significantly affected by either race or SNP status. All Caucasian controls with D1472H were heterozygous, while 14% of the African-American controls were homozygous. The mean RCo/Ag for the homozygous controls was 0.71, compared to 0.86 for the AA heterozygous controls (p<0.025). In order to determine if the exon 28 SNPs intrinsically altered the measurement of VWF, the 3 SNPs were engineered into recombinant VWF and expressed in HEK293T cells. VWF Ag and RCo were performed on the purified expressed VWF. The RCo/Ag ratios for the recombinant expressed VWF were decreased for 1380V and 1472H, while the construct containing all 3 SNPs showed an even lower ratio (59% of wild-type RCo/Ag ratio). These data suggest that specific exon 28 SNPs may contribute to low RCo/Ag ratios, especially in the African-American population. Since the RCo assay involves ristocetin binding to VWF, mutations (and polymorphisms) in VWF may affect the measurement of “VWF activity” by this assay and might not reflect true hemorrhagic risk.

scholarly journals Association of Obesity on Laboratory Profiles of Individuals with Type 1 Von Willebrand Disease and Low VWF in the Athn Dataset

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2415-2415
Author(s):  
Beverly Schaefer ◽  
Dunlei Cheng ◽  
Peter A. Kouides
Keyword(s):  
Research Funding ◽  
Management Practices ◽  
Laboratory Data ◽  
Von Willebrand Disease ◽  
Data Set ◽  
Significant Difference ◽  
Prevalence Of Obesity ◽  
Von Willebrand ◽  
The Impact

Introduction: Obesity is associated with endothelial dysfunction, hemostatic and fibrinolytic disturbances. The relationship between obesity and elevated Von Willebrand Factor (VWF) is complex and not fully elucidated. There is a significant knowledge gap regarding the impact of BMI on VWF levels. Given the proinflammatory effect associated with abdominal obesity, we hypothesized that there would be an increased prevalence of obesity among individuals with Low VWF (LVWF) compared to Type 1 Von Willebrand Disease (T1VWD) in the ATHN (American Thrombosis and Hemostasis Network) dataset. Methods: A retrospective review of de-identified patients included in the ATHN dataset as of March 2018 was performed. The dataset was queried for all patients with a diagnosis of "T1VWD," who were over 18 years of age when labs were drawn and when BMI was recorded, who had VWF Ristocetin cofactor (RCO) levels <50 IU/dL and who had BMI entered within 24 months of the date of lab entry. Subjects were categorized with VWF RCO ≤30% as T1VWD and 30-50% as LVWF. We used the NIH definitions for BMI (BMI<18.5, underweight; 18.5-24.9, normal; 25-29.9, overweight; 30-39.9, obese; BMI >40, extremely obese). Results: Of the 6939 patients with T1VWD in the ATHN dataset, 4754 patients had VWF RCO <50%, 1019 were above the age of 18, resulting in 548 evaluable subjects with BMI and laboratory metrics. There were 186 patients in the T1VWD cohort, and 362 patients in the LVWF cohort, with a Female:Male ratio >3:1 (Table 1). BMI was treated as a continuous measurement and on bivariate analysis there was not a statistically significant difference (p=0.593), with mean BMI 28.2 (17.2-52) in T1VWD and 28.6 (15.3-55.4) in LVWF. Prevalence of obesity (BMI ≥30) was not significantly different between cohorts (T1VWF 32% vs. LVWF 36%, p=0.345, Table 1). The prevalence of obesity by age (18-39, 40-59, >60 years) was similar among both cohorts with the exception of a larger proportion of obese individuals over the age of 60 in the LVWF cohort (63% vs 25%). Mean FVIII level for LVWF cohort was significantly higher compared to that for T1VWD cohort (80% vs. 53%; p<0.001). In addition, extremely obese patients had an elevated mean FVIII level compared to overweight patients (81% vs. 60%; p=0.041, Table 2). Among individuals with BMI≥30, there were increased rates for Black race (p=0.013), and Medicaid and Medicare rates (p=0.028) when compared to non-obese individuals (Table 3). While rates of obesity are known to vary regionally, no conclusions could be drawn as there was disproportionate geographic clustering in states with well-established hemophilia treatment centers. Conclusions: Our analysis identified that 34.8% of adults categorized as VWD in the ATHN data set are obese, with similar prevalence among T1VWD and LVWF. This finding, coupled with associated race, ethnic and socioeconomic risk factors can help prioritize prevention and weight management as a critical component of the comprehensive care model. Increasing degree of obesity may be associated with elevated FVIII, and should be studied prospectively in larger cohorts and the potential impact on cardiovascular risk. Limitations of this analysis include incomplete laboratory data, lack of longitudinal laboratory data, unknown potential confounders including pregnancy or medication effect, and non-uniform geographic distribution of patients. Further research is needed to evaluate the impact of obesity on bleeding phenotype, bleeding related complications, and management practices, as well as the effects of weight change on VWF and FVIII levels. Disclosures Schaefer: Siemens: Research Funding; Stago: Research Funding.

(Preprint)

2018 ◽  
Author(s):  
Natalia Banasik ◽  
Dariusz Jemielniak ◽  
Wojciech P?dzich
Keyword(s):  
Medical Condition ◽  
Extended Period ◽  
Well Being ◽  
Marginal Effect ◽  
Life Duration ◽  
Significant Difference ◽  
The Mean ◽  
Academic Teachers ◽  
Length Of Life ◽  
The Impact

BACKGROUND There have been mixed results of the studies checking whether prayers do actually extend the life duration of the people prayed for. Most studies on the topic included a small number of prayers and most of them focused on people already struggling with a medical condition. Intercessory prayer’s influence on health is of scholarly interest, yet it is unclear if its effect may be dependent on the number of prayers for a named individual received per annum. OBJECTIVE We sought to examine if there is a noticeable increased longevity effect of intercessory prayer for a named individual’s well-being, if he receives a very high number of prayers per annum for an extended period. METHODS We retrieved and conducted a statistical analysis of the data about the length of life for 857 Roman Catholic bishops, 500 Catholic priests, and 3038 male academics from the US, France, Italy, Poland, Brazil, and Mexico. We obtained information for these individuals who died between 1988 and 2018 from Wikidata, and conducted an observational cohort study. Bishops were chosen for the study, as they receive millions of individual prayers for well being, according to conservative estimates. RESULTS There was a main effect for occupation F(2, 4391) = 4.07, p = .017, ηp 2 = .002, with pairwise comparisons indicating significant differences between the mean life duration of bishops (M=30489) and of priests (M=29894), but none between the academic teachers (M=30147) and either of the other groups. A comparison analysis between bishops from the largest and the smallest dioceses showed no significant difference t(67.31)=1.61, p = .11. Our main outcome measure is covariance of the mean length of life in each of the categories: bishops, priests, academic teachers, controlled for nationality. CONCLUSIONS The first analysis proved that bishops live longer than priests, but due to a marginal effect size this result should be treated with caution. No difference was found between the mean length of life of bishops from the largest and the smallest dioceses. We found no difference between bishops and male academics. These results show that the impact of intercessory prayers on longevity is not observable.

scholarly journals The impact of COVID-19 infection on hip fracture 30-day mortality

Trauma ◽  
2021 ◽  
pp. 146040862094972
Author(s):  
Ahmed Fadulelmola ◽  
Rob Gregory ◽  
Gavin Gordon ◽  
Fiona Smith ◽  
Andrew Jennings
Keyword(s):  
Hip Fracture ◽  
Hip Fractures ◽  
Hospital Admissions ◽  
The Elderly ◽  
Primary Outcome Measure ◽  
Time To Death ◽  
Significant Difference ◽  
The Mean ◽  
The Impact ◽  
Mean Time

Introduction: A novel virus, SARS-CoV-2, has caused a fatal global pandemic which particularly affects the elderly and those with comorbidities. Hip fractures affect elderly populations, necessitate hospital admissions and place this group at particular risk from COVID-19 infection. This study investigates the effect of COVID-19 infection on 30-day hip fracture mortality. Method: Data related to 75 adult hip fractures admitted to two units during March and April 2020 were reviewed. The mean age was 83.5 years (range 65–98 years), and most (53, 70.7%) were women. The primary outcome measure was 30-day mortality associated with COVID-19 infection. Results: The COVID-19 infection rate was 26.7% (20 patients), with a significant difference in the 30-day mortality rate in the COVID-19-positive group (10/20, 50%) compared to the COVID-19-negative group (4/55, 7.3%), with mean time to death of 19.8 days (95% confidence interval: 17.0–22.5). The mean time from admission to surgery was 43.1 h and 38.3 h, in COVID-19-positive and COVID-19-negative groups, respectively. All COVID-19-positive patients had shown symptoms of fever and cough, and all 10 cases who died were hypoxic. Seven (35%) cases had radiological lung findings consistent of viral pneumonitis which resulted in mortality (70% of mortality). 30% ( n = 6) contracted the COVID-19 infection in the community, and 70% ( n = 14) developed symptoms after hospital admission. Conclusion: Hip fractures associated with COVID-19 infection have a high 30-day mortality. COVID-19 testing and chest X-ray for patients presenting with hip fractures help in early planning of high-risk surgeries and allow counselling of the patients and family using realistic prognosis.

The Impact of Medical Comorbidities on Patient Satisfaction in Chronic Rhinosinusitis

2021 ◽  
pp. 000348942110157
Author(s):  
Amarbir S. Gill ◽  
Joshua Hwang ◽  
Angela M. Beliveau ◽  
Jeremiah A. Alt ◽  
Edward Bradley Strong ◽  
...  
Keyword(s):  
Patient Satisfaction ◽  
Hearing Impairment ◽  
Chronic Rhinosinusitis ◽  
Medical Comorbidities ◽  
Patient Demographics ◽  
Significant Difference ◽  
Comorbidity Index ◽  
The Mean ◽  
Therapy Compliance ◽  
The Impact

Background: Patient satisfaction has a significant bearing on medical therapy compliance and patient outcomes. The purpose of this study was to (1) describe patient satisfaction, as characterized by the Patient Satisfaction Questionnaire-18 (PSQ-18), in the care of patients with chronic rhinosinusitis (CRS) and (2) analyze the impact of comorbidities on satisfaction using the functional comorbidity index (FCI). Methods: Patient demographics, disease severity measures, and PSQ-18 scores for patients with CRS presenting to a tertiary rhinology clinic between November 2019 and April 2020 were collected and analyzed. FCI was calculated retrospectively using the electronic medical record; individual comorbidities were tabulated. Spearman’s correlations followed by multivariate regression was used to assess the relationship between medical comorbidities and PSQ-18. Results: Sixty-nine patients met criteria for analysis. There were no significant differences in age, gender, and Sinonasal Outcomes Test-22 scores between CRS patients with (CRSwNP) and without (CRSsNP) nasal polyps. There was no significant difference in the mean FCI for patients with CRSwNP versus CRSsNP (5.1 and 4.3, respectively) ( P = .843). Similarly, there was no significant difference in the mean sum PSQ-18 score (78/100 in both) between these cohorts ( P = .148). The mean sum PSQ-18 score was not significantly associated with anxiety ( P = .728), depression ( P = .624), or FCI ( P = .282), but was significantly associated with hearing impairment ( P < .001). Conclusion: Patient satisfaction in the care of CRS is generally high with a diagnosis of comorbid hearing impairment demonstrating a negative association with satisfaction in this cohort.

scholarly journals Impact of Remote Teaching on Japanese Medical University Students' Sleeping Habits : a Longitudinal Study

2021 ◽  
Author(s):  
Reiko Hori ◽  
Eiji Shibata ◽  
Iwao Okajima ◽  
Masahiro Matsunaga ◽  
Tomohiro Umemura ◽  
...  
Keyword(s):  
University Students ◽  
Sleep Duration ◽  
Sleep Problems ◽  
Significant Difference ◽  
Delayed Sleep Phase ◽  
The Mean ◽  
Delayed Sleep ◽  
Sleeping Habits ◽  
Medical University ◽  
The Impact

Abstract Background: The coronavirus disease 2019 (COVID-19) pandemic has changed our daily life. Owing to the imposed restrictions, many educational facilities have introduced remote teaching. This study aims to understand the impact of remote teaching on Japanese university students' sleeping habits.Methods: The participants were medical university students. We used data from an ongoing longitudinal sleeping habits survey. For 684 participants who enrolled in the university during 2018–2020, multilevel analyses of sleep duration during weekdays and weekends across 3 years were conducted, adjusting for gender, grade, place of stay, sleep problems and lifestyle habits. Results: Among the participants, 356 male (mean ± standard deviation: 22 ± 3, 18–37 years old) and 288 female (22 ± 3, 18–32 years old) students in 2018, 365 male (24 ± 3,18–36 years old) and 284 female (22 ± 2, 18–33 years old) students in 2019, and 226 male (20 ± 3,18-36 years old) and 167 female (21 ± 2, 18–34 years old) students in 2020 answered the questionnaire. The mean sleep duration during weekdays (in minutes) was 407.6 ± 60.3 in 2018, 406.9 ± 63.0 in 2019, and 417.3 ± 80.9 in 2020. The mean sleep duration during weekends (in minutes) was 494.5 ± 82.5 in 2018, 488.3 ± 87.9 in 2019, and 462.3 ± 96.4 in 2020. The analysis showed that sleep duration during weekdays was associated with the place of stay and survey year. Moreover, students reported significantly longer sleep duration during weekdays in 2020 than 2019, but no significant difference in sleep duration between 2018 and 2019. Sleep duration during weekends was found to be associated with the survey year, gender and always doing something before going to bed. Sleep duration during weekends was shorter in 2020 than 2019 and longer in male students and students who always do something before going to bed. Ten students were reported to have a delayed sleep phase in 2020. Conclusions: Students' sleep duration increased during weekdays and decreased during weekends in 2020. This difference could be explained by the COVID-19 pandemic and the introduction of remote teaching.

scholarly journals Collagen Binding Provides a Sensitive Screen for Variant von Willebrand Disease

2013 ◽  
Vol 59 (4) ◽  
pp. 684-691 ◽  
Author(s):  
Veronica H Flood ◽  
Joan Cox Gill ◽  
Kenneth D Friedman ◽  
Pamela A Christopherson ◽  
Paula M Jacobi ◽  
...  
Keyword(s):  
Gel Electrophoresis ◽  
Reference Intervals ◽  
Von Willebrand Disease ◽  
Type Iii Collagen ◽  
Healthy Controls ◽  
Collagen Binding ◽  
Vessel Injury ◽  
Clinical Biology ◽  
Von Willebrand

BACKGROUND von Willebrand factor (VWF) is a multimeric protein that binds platelets and collagen, facilitating hemostasis at sites of vessel injury. Measurement of VWF multimer distribution is critical for diagnosis of variant von Willebrand disease (VWD), particularly types 2A and 2B, but the typical measurement by gel electrophoresis is technically difficult and time-consuming. A comparison of VWF collagen binding (VWF:CB) and VWF multimer distribution was performed to evaluate the utility of VWF:CB as a diagnostic test. METHODS Participants were enrolled in the Zimmerman Program for the Molecular and Clinical Biology of VWD. VWF:CB was analyzed with type III collagen and multimer distribution by agarose gel electrophoresis. The study population included 146 healthy controls, 351 individuals with type 1 VWD, and 77 with type 2 VWD. Differences between individuals with multimer group results within (controls) and outside the reference intervals were assessed with Mann–Whitney tests. RESULTS The mean VWF:CB/VWF antigen ratio was 1.10 for individuals with multimer distribution within the reference intervals and 0.51 for those with multimer distribution outside the reference intervals (P &lt; 0.001). Sensitivity of VWF:CB for multimer abnormalities was 100% for healthy controls, 99% for patients with type 1, and 100% for patients with type 2A and type 2B VWD using a VWF:CB/VWF antigen cutoff ratio of 0.6, and decreased to 99% for all patients with a ratio of 0.7. With the exception of individuals with novel or unclassified mutations, the VWF:CB was able to correctly categorize participants with variant VWD. CONCLUSIONS These findings suggest that VWF:CB may substitute for multimer distribution in initial VWD testing, although further studies are needed to validate the clinical utility of VWF:CB.

Abstract 321: Impact Of Chronic Kidney Disease On Heart Failure Outcomes In A Minority Cohort

2014 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
TAOPHEEQ MUSTAPHA ◽  
VARIJA BHOGIREDDY ◽  
HARTMAN MADU ◽  
ADU BOACHIE ◽  
ABDUL OSENI ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
African American ◽  
Kidney Disease ◽  
Prognostic Impact ◽  
Mortality And Morbidity ◽  
Ckd Stage ◽  
Significant Difference ◽  
The Mean ◽  
The Impact

BACKGROUND: Heart failure (HF) and Chronic kidney disease (CKD) are major public health problems that often co-exist with a resultant high mortality and morbidity. Most of the studies evaluating their reciprocal prognostic impact have focused on mortality in majority populations. There is limited literature on the impact of CKD on HF morbidities in ethnic minorities. AIMS: Our study seeks to compare HF outcomes in patients with or without CKD in an African-American predominant cohort. METHODS: We obtained data from the NGH at Meharry Heart Failure Cohort; a comprehensive retrospective HF database comprised of patient care data (HF admissions, non-HF admissions, and emergency room visits) were assessed from January 2006 to December 2008. The study group consist of 306 subjects with a mean age of 65±15 years. 81% were African-American (AA), 19% Caucasian and 48.5% are females. Following the NKF KDOQI guidelines, 5 stages of CKD were outlined based on GFR. RESULTS: The overall prevalence of CKD in this population is 54.2%. CKD stage 1 was most prevalent with 45.8%, prevalence for stages 2-5 are 21.6%, 18.3%, 9.5% and 4.9% respectively. The comparison of the mean of ER visits, non HF hospitalizations and HF hospitalizations between normal and CKD patients was done using independent t-test and showed no significant difference in the mean number of ER visits (p=0.564), or HF hospitalizations(p=0.235). However, there is a statistically significant difference in the mean number of non -HF hospitalizations between normal and CKD patients (p=0.031). CONCLUSION: This study shows that the prevalence of CKD in this minority -predominant HF cohort is similar to prior studies in majority populations. However, only the non-HF hospitalizations were significantly increased in the CKD group. Future prospective studies will be needed to define the implications of this in the management of HF patients with CKD.

scholarly journals Systemic anti-commensal response to fungi analyzed by flow cytometry is related to gut mycobiome ecology

Microbiome ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Alicia Moreno-Sabater ◽  
Gaelle Autaa ◽  
Delphine Sterlin ◽  
Amenie Jerbi ◽  
Remy Villette ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Alpha Diversity ◽  
Fungal Species ◽  
Individual Variability ◽  
Humoral Immune ◽  
Healthy Donors ◽  
Significant Difference ◽  
Genus Richness ◽  
Humoral Responses ◽  
The Impact

Abstract Background Interest for the study of gut mycobiota in relation with human health and immune homeostasis has increased in the last years. From this perspective, new tools to study the immune/fungal interface are warranted. Systemic humoral immune responses could reflect the dynamic relationships between gut mycobiota and immunity. Using a novel flow cytometry technology (Fungi-Flow) to determine immunoglobulin (Ig) responses to fungi, we studied the relationships between gut mycobiota and systemic humoral anti-commensal immunity. Results The Fungi-Flow method allows a sensitive and specific measurement of systemic IgG responses against 17 commensal and environmental fungi from the two main divisions; Ascomycota and Basidiomycota. IgG responses exhibited a high inter-individual variability. Anti-commensal IgG responses were contrasted with the relative abundance, alpha-diversity, and intra-genus richness of fungal species in gut mycobiota of twenty healthy donors. Categorization of gut mycobiota composition revealed two differentiated fungal ecosystems. Significant difference of anti-Saccharomyces systemic IgG responses were observed in healthy donors stratified according to the fungal ecosystem colonizing their gut. A positive and significant correlation was observed between the variety of IgG responses against fungal commensals and intestinal alpha-diversity. At the level of intra-genus species richness, intense IgG responses were associated with a low intra-genus richness for known pathobionts, but not commensals. Conclusions Fungi-Flow allows an easy and reliable measure of personalized humoral responses against commensal fungi. Combining sequencing technology with our novel Fungi-Flow immunological method, we propose that there are at least two defined ecosystems in the human gut mycobiome associated with systemic humoral responses. Fungi-Flow opens new opportunities to improve our knowledge about the impact of mycobiota in humoral anti-commensal immunity and homeostasis.

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