scholarly journals The Impact of Age and BMI on the VWF/ADAMTS13 Axis and Simultaneous Thrombin and Plasmin Generation in Hospitalized COVID-19 Patients

2022 ◽  
Vol 8 ◽  
Author(s):  
Kiruphagaran Thangaraju ◽  
Upendra Katneni ◽  
Imo J. Akpan ◽  
Kenichi Tanaka ◽  
Tiffany Thomas ◽  
...  

Aging and obesity independently contribute toward an endothelial dysfunction that results in an imbalanced VWF to ADAMTS13 ratio. In addition, plasma thrombin and plasmin generation are elevated and reduced, respectively, with increasing age and also with increasing body mass index (BMI). The severity risk of Corona Virus Disease 2019 (COVID-19) increases in adults older than 65 and in individuals with certain pre-existing health conditions, including obesity (>30 kg/m2). The present cross-sectional study focused on an analysis of the VWF/ADAMTS13 axis, including measurements of von Willebrand factor (VWF) antigen (VWF:AG), VWF collagen binding activity (VWF:CBA), Factor VIII antigen, ADAMTS13 antigen, and ADAMTS13 activity, in addition to thrombin and plasmin generation potential, in a demographically diverse population of COVID-19 negative (−) (n = 288) and COVID-19 positive (+) (n = 543) patient plasmas collected at the time of hospital presentation. Data were analyzed as a whole, and then after dividing patients by age (<65 and ≥65) and independently by BMI [<18.5, 18.5–24.9, 25–29.9, >30 (kg/m2)]. These analyses suggest that VWF parameters (i.e., the VWF/ADAMTS13 activity ratio) and thrombin and plasmin generation differed in COVID-19 (+), as compared to COVID-19 (−) patient plasma. Further, age (≥65) more than BMI contributed to aberrant plasma indicators of endothelial coagulopathy. Based on these findings, evaluating both the VWF/ADAMTS13 axis, along with thrombin and plasmin generation, could provide insight into the extent of endothelial dysfunction as well as the plasmatic imbalance in coagulation and fibrinolysis potential, particularly for at-risk patient populations.

2004 ◽  
Vol 92 (12) ◽  
pp. 1320-1326 ◽  
Author(s):  
Cristina Farías ◽  
María Amaral ◽  
Ana Kempfer ◽  
Roberto Votta ◽  
Carlos Marchese ◽  
...  

SummaryADAMTS13 dysfunction has been involved in the pathogenesis of Thrombotic Thrombocytopenic Purpura. This disorder occurs more frequently in women and, in 13% of them, is associated with pregnancy. However, there is little information on the protease behaviour in normal pregnancy. We studied von Willebrand factor and ADAMTS13 activity changes in normal non-pregnant, pregnant and post-delivery women. Fifty-five non-pregnant women, normal blood bank donors, who were not taking contraceptive pills were included as controls. A prospective cross-sectional study of 270 normal pregnant and post-delivery women was carried out. ADAMTS13 activity decreased progressively as from the period of 12–16 weeks up to the end of early puerperium (mean 52%, range 22–89, p < 0.0001), to increase slightly thereafter. Nulliparous presented mildly lower levels of ADAMTS13 activity than parous women (65% vs. 83%, p=0.0003), and primigravidae than multigravidae between 6–11 weeks up to 17–23 weeks of pregnancy (69% vs. 80%, p=0.005). Although in all women the protease levels were the same by blood groups, the O blood group non-pregnant women showed a higher mean of ADAMTS13 activity than those non-O (78% vs. 69%, p= 0.064). Our results suggest that the changing levels of protease activity during pregnancy and puerperium, induced by unidentified mechanisms, could render the peripartum time more vulnerable to developed thrombotic microangiopathies.


2020 ◽  
Vol 13 (3) ◽  
pp. 157-167 ◽  
Author(s):  
Justin van der Tas ◽  
Thomas Dodson ◽  
Daniel Buchbinder ◽  
Stefano Fusetti ◽  
Michael Grant ◽  
...  

Study Design: The COrona VIrus Disease-19 (COVID-19) pandemic has disrupted craniomaxillofacial (CMF) surgeons practice worldwide. We implemented a cross-sectional study and enrolled a sample of CMF surgeons who completed a survey. Objective: To measure the impact that COVID-19 has had on CMF surgeons by (1) identifying variations that may exist by geographic region and specialty and (2) measuring access to adequate personal protective equipment (PPE) and identify factors associated with limited access to adequate PPE. Methods: Primary outcome variable was availability of adequate PPE for health-care workers (HCWs) in the front line and surgeons. Descriptive and analytic statistics were computed. Level of statistical significance was set at P < .05. Binary logistic regression models were created to identify variables associated with PPE status (adequate or inadequate). Results: Most of the respondents felt that hospitals did not provide adequate PPE to the HCWs (57.3%) with significant regional differences ( P = .04). Most adequate PPE was available to surgeons in North America with the least offered in Africa. Differences in PPE adequacy per region ( P < .001) and per country ( P < .001) were significant. In Africa and South America, regions reporting previous virus outbreaks, the differences in access to adequate PPE evaporated compared to Europe ( P = .18 and P = .15, respectively). Conclusion: The impact of COVID-19 among CMF surgeons is global and adversely affects both clinical practice and personal lives of CMF surgeons. Future surveys should capture what the mid- and long-term impact of the COVID-19 crisis will look like.


2016 ◽  
Vol 49 (8) ◽  
pp. 933-955 ◽  
Author(s):  
N. Smith ◽  
F. Kinnafick ◽  
S. J. Cooley ◽  
G. M. Sandal

Results from previous studies suggest that stressful environmental conditions such as those faced on expedition may result in psychological growth. Building on previous research, the present cross-sectional study examined the role of personality and perceived stress in relation to post-expedition growth. Eighty-three participants who had completed a mountaineering expedition responded to measures of stress, personality, growth, well-being, and resilience. Findings implicate perceived stress, and personality dimensions of agreeableness and openness, in post-expedition growth. Growth was associated with well-being but distinct from psychological resilience, highlighting the need to consider growth and resilience independently. Present findings support the proposition that stressful expedition environments may promote positive psychological adjustment and identify factors that may influence this change. Research is needed to delineate the impact of other variables, such as coping, on changes that occurs during the post-expedition phase. Such research holds relevance for maintaining health following immersion in extreme and unusual environments.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1425-1425
Author(s):  
Bruce A. Schwartz ◽  
Birte Fuchs ◽  
Christoph Kannicht ◽  
Barbera Solecka ◽  
Mario Kröning

Abstract Abstract 1425 Introduction: The characteristic multimer pattern of plasmatic von Willebrand factor (VWF) results from asymmetric cleavage by the processing metalloprotease ADAMTS13 between Y1605/M1606 within the VWF A2 domain. In normal plasma, characteristic species of various multimeric sizes with flanking satellite bands (triplets) encircling the major band on VWF multimer gels are present. The faster and slower migrating bands encompassing a VWF multimer lack one N-terminal fragment or possess an additional N-terminal fragment, respectively. Even though the distribution of VWF satellite bands is significantly altered in some types of von Willebrand disease (VWD) and several commercial VWF concentrates, the impact of triplet structure on VWF function has not been investigated so far. Methods: Four commercially available VWF concentrates were analyzed with respect to ADAMTS13 content as well as VWF multimer- and triplet structure using agarose gel electrophoresis. ADAMTS13 activity was quantified by the fluorescence resonance energy transfer (FRET) assay. VWF zymogram gels were used to test for ADAMTS13 activity. Samples composed of different VWF triplet distribution but comparable VWF multimers were obtained by fractionation of plasmatic VWF using heparin affinity chromatography. VWF affinity to collagen was measured by surface plasmon resonance (SPR). Results: VWF concentrates markedly differed in their content of ADAMTS13 antigen and activity. A higher ADAMTS13 content correlated with an increased portion of the proteolyzed faster migrating VWF triplet band. The degree of VWF proteolysis, i.e. lack of an additional N-terminal fragment, correlated with a decreased collagen binding level measured by SPR. Conclusion: Proteolytic cleavage of N-terminal domains of VWF resulting in a higher content of faster migrating satellite bands affects the function of VWF. The impact of VWF N-terminal domains on collagen binding and potential clinical consequences of enhanced proteolysis in commercial concentrates has to be further evaluated. Disclosures: Schwartz: Octapharma: Employment. Fuchs:Octapharma: Employment. Kannicht:Octapharma: Employment. Solecka:Octapharma: Employment. Kröning:Octapharma: Employment.


2014 ◽  
Vol 112 (08) ◽  
pp. 297-303 ◽  
Author(s):  
Ilaria Mancini ◽  
Carla Valsecchi ◽  
Luca Lotta ◽  
Louis Deforche ◽  
Silvia Pontiggia ◽  
...  

SummaryCollagen-binding activity (CBA) and FRETS-VWF73 assays are widely adopted methods for the measurement of the plasmatic activity of ADAMTS13, the von Willebrand factor (VWF) cleaving-protease. Accurately assessing the severe deficiency of ADAMTS13 is important in the management of thrombotic thrombocytopenic purpura (TTP). However, non-concordant results between the two assays have been reported in a small but relevant percentage of TTP cases. We investigated whether CBA or FRETS-VWF73 assay reflects ADAMTS13 proteolytic activity in acquired TTP patients with non-concordant measurements. Twenty plasma samples with non-concordant ADAMTS13 activity results, <10% using FRETS-VWF73 and ≥20% using CBA, and 11 samples with concordant results, <10% using either FRETS-VWF73 and CBA assays, were analysed. FRETS-VWF73 was performed in the presence of 1.5 M urea. ADAMTS13 activities were also measured under flow conditions and the VWF multimer pattern was defined in order to verify the presence of ultra-large VWF due to ADAMTS13 deficiency. In FRETS-VWF73 assay with 1.5 M urea, ADAMTS13 activity significantly increased in roughly 50% of the samples with non-concordant results, whereas it remained undetectable in all samples with concordant measurements. Under flow conditions, all tested samples showed reduced ADAMTS13 activity. Finally, samples with non-concordant results showed a ratio of high molecular weight VWF multimers higher than normal. Our results support the use of FRETS-VWF73 over CBA assay for the assessment of ADAMTS13 severe deficiency and indicate urea as one cause of the observed differences.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Lerine B Eldin ◽  
Asmaa W Abd Elaziz ◽  
Dina A Ragab ◽  
Karim A Abdelhady

Abstract Background Ruptured oesophageal varices (OVs) is a major cause of mortality in Portal hypertension (PHT) patients, It has been a great issue of interest and research to screen and early detect OVs via oesophageal varices non-invasive methods. Objective The aim of this study was to assess the reliability of measuring plasma von willibrand factor antigen (VWF-Ag) for prediction of the occurrence of oesophageal varices in patients with portal hypertension. Subjects & Methods This was a prospective cross-sectional study, done on 47 children with portal hypertension. The children were recruited from Pediatrics Hepatology clinic, Ain Shams University. Patient’s data was collected including age, sex, etiology and duration of PHT, along with medical treatment. Also an upper GIT endoscope, abdominal doppler ultrasound, and laboratory tests including measuring of plasma VWF-Ag were done to each patient. Then the children were divided based on their endoscopic findings into two groups; variceal group which included 37 patients, and a nonvariceal group which included 10 patients Results: The results of our study revealed an elevated plasma VWF-Ag in patients with oesophageal varices, whilst normal levels of plasma VWF-Ag in the non-variceal patients. In addition, there was a direct positive correlation between increased plasma VWF-Ag and the degree of oesophageal varices. Conclusion Since the plasma VWF-Ag level correlates with the presence and degree of OVs, it can be used as a noninvasive indicator of the presence and degree of OVs, However, further studies using larger sample might be needed to support this.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5312-5312
Author(s):  
Lei Shen ◽  
Guoyuan Lu ◽  
Ningzheng Dong ◽  
Liqiong Jiang ◽  
Zhenni Ma ◽  
...  

Abstract Abstract 5312 Patients with chronic kidney disease (CKD) have increased risks of endothelial dysfunction and thrombosis. Systemic inflammation may contribute to the endothelial dysfunction and accelerated thrombosis observed in CKD patients. von Willebrand factor (VWF), a well-known index of endothelial damage, has been reported to increase both in CKD and inflammatory states. ADAMTS13 is a specific VWF-cleaving protease, and some reports suggested that the ratio of VWF and ADAMTS13 maybe more useful in the diagnosis and treatment evaluation of patients in the prothrombotic state. So we assessed the relationships among endothelial dysfunction, ADAMTS13 activity, and levels of inflammatory cytokines in CKD patients. CKD patients were classified into 3 groups: chronic glomerulonephritis group (CGN, n = 31), idiopathic nephritic syndrome group (NS, n = 32), and lupus nephritis group (LN, n = 41). We measured the plasma levels of TNF-α, VWF antigen (VWF:Ag), and ADAMTS13 activity by using an ELISA-based method in CKD patients (n = 104) and normal controls (n = 32). The ratio of the VWF:Ag level to ADAMTS13 activity was calculated. The VWF:Ag level was significantly higher and the ADAMTS13 activity was significantly lower in all the disease groups than in the controls (P < 0.01). ADAMTS13 activity was lower in the NS group than in the CGN and LN groups (P < 0.05) (Table 1). The TNF-α (pg/mL) level was higher in the CKD group than in the control group (CGN: 3.19 ± 1.01; NS: 3.26 ± 1.18; LN: 3.24 ± 1.24; Control: 2.27 ± 1.23; P < 0.01; P < 0.01). TNF-α was positively correlated with the VWF:Ag level (r = 0.242, P = 0.013) and negatively correlated with the glomerular filtration rate (GFR) (r = −0.193, P = 0.049). ADAMTS13 activity was negatively correlated with the cholesterol level in CKD patients (r = −0.2, P = 0.042). TNF-α level in CKD was positively correlated with the VWF:Ag level and negatively correlated with GFR, which suggests that inflammation might be a major cause of endothelial dysfunction and an index for renal function. The VWF:Ag level increased and ADAMTS13 activity decreased in CKD patients, which indicates that CKD leads to a prothrombotic state. Table 1. The plasma VWF:Ag level, ADAMTS13 activity, and the VWF/ADAMTS13 ratio in the CGN, NS, LN, and control groups N VWF (%) ADAMTS13 (%) VWF/ADAMTS13 CGN 31 198.25 ± 140.20** 61.93 ± 22.47**# 3.83 ± 3.29** NS 32 149.94 ± 74.50** 48.87 ± 18.63** 3.42 ± 1.59** LN 41 234.75 ± 134.91**## 67.81 ± 22.30**## 3.79 ± 2.52** CONTROL 32 99.55 ± 21.37 94.37 ± 23.66 1.12 ± 0.37 vs. CONTROL ** P < 0.01; vs. NS ## p < 0.01, # P < 0.05 Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2003 ◽  
Vol 101 (3) ◽  
pp. 946-948 ◽  
Author(s):  
Rosemarie A. Reiter ◽  
Paul Knöbl ◽  
Katalin Varadi ◽  
Peter L. Turecek

Abstract von Willebrand factor–cleaving protease (ADAMTS13) cleaves von Willebrand factor (VWF) and regulates its physiologic function. To investigate the relation between ADAMTS13 activity and VWF, we compared ADAMTS13 activity with the VWF-related parameters VWF antigen (VWF:Ag), VWF collagen-binding activity (VWF:CBA), VWF-propeptide, proVWF, and VWF multimeric composition in 10 healthy volunteers and 3 patients with type 1 von Willebrand disease before and after infusing 0.3 μg/kg desmopressin. The VWF-related parameters in the volunteers increased 60 minutes after start of infusion by 3.7-fold for VWF:Ag, 7.2-fold for propeptide, and 2.2-fold for VWF:CBA. Unusually large VWF multimers and traces of proVWF appeared. The ADAMTS13 activity decreased to about half the initial value. After 24 hours values returned to baseline. Patients with type 1 von Willebrand disease showed similar results. We conclude that the inverse correlation between ADAMTS13 and VWF-related parameters suggests a consumption of ADAMTS13 after the desmopressin-induced release of higher multimers of VWF.


2021 ◽  
Vol 14 (4) ◽  
pp. 2235-2244
Author(s):  
Ainsy Goldlin T. J ◽  
Prakash M

Background: Corona Virus Disease 2019 (COVID-19) has brought several impacts on the health of people. The infodemic which accompanied the pandemic can lead to cyberchondria, fear and anxiety accompanying excessive online search of COVID-19 related information. Most of the people try to avoid getting infected with this virus by taking adequate protective measures. Hence the aim of this study was to analyze the impact of COVID-19 related cyberchondria on self-medication and self care. Materials and Methods: An online cross-sectional semi-structured questionnaire based study was done and a total of 323 responses were obtained. Participants were segregated into two clusters based on the cyberchondria severity score which included four constructs using k-means cluster analysis considering the score obtained in each construct. The impact of cyberchondria on self care and self care among medical practitioners between the clusters was analyzed using independent t-test. Qualitative data were analyzed using descriptive statistics. Results: This study found that 35% of the participants were categorized in the cluster with high cyberchondria score. A marked proportion of the participants who have taken self-medication for COVID-19 prophylaxis belonged to this cluster. A statistically significant difference was observed in the mean of the scores used to assess self care between the clusters (p = 0.003) whereas no significant difference was observed among registered medical practitioners (p=0.222). Conclusion: Anxiety related with excessive online COVID-19 information seeking behaviour had effects in terms of enhanced self care and self-medication in the respondents. Hence it is important to use internet wisely for self well being.


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