Reduced peak, but no diurnal variation, in thrombin generation upon melatonin supplementation in tetraplegia

2015 ◽  
Vol 114 (11) ◽  
pp. 964-968 ◽  
Author(s):  
Anders Dahm ◽  
Grethe Skretting ◽  
Marie-Christine Mowinckel ◽  
Annicke Stranda ◽  
Bjarne Østerud ◽  
...  
Keyword(s):  
Diurnal Variation ◽  
Thrombin Generation ◽  
Study Groups ◽  
Sleep Cycle ◽  
Healthy Individuals ◽  
Time To Peak ◽  
Cat Assay ◽  
Increased Risk ◽  
Significant Diurnal Variation

SummaryTetraplegic patients have increased risk of venous thrombosis despite anti-thrombotic prophylaxis. Moreover, they have blunted plasma variations in melatonin and altered diurnal variation of several haemostatic markers, compared with able-bodied. However, whether healthy individuals and tetraplegic patients, with or without melatonin, display abnormalities in thrombin generation during a 24-hour (h) cycle, is unknown. We therefore used the Calibrated Automated Thrombogram (CAT) assay to examine diurnal variations and the possible role of melatonin in thrombin generation. Six men with long-standing complete tetraplegia were included in a randomised placebo-controlled cross-over study with melatonin supplementation (2 mg, 4 consecutive nights), whereas six healthy, able-bodied men served as controls. Ten plasma samples were collected frequently during a 24-h awake/sleep cycle. No significant diurnal variation of any of the measured CAT indices was detected in the three study groups. Whereas endogenous thrombin potential (ETP) was independent (p > 0.05) of whether the tetraplegic men received melatonin or placebo, melatonin decreased (p = 0.005) peak values in tetraplegia compared with those given placebo. Able-bodied men had lower (p = 0.019) ETP and Lag-Time (p = 0.018) compared with tetraplegics receiving placebo. Neither the Time-to-Peak nor the Start-Tail was affected (p > 0.05) by melatonin in tetraplegia. In conclusion, indices of thrombin generation are not subjected to diurnal variation in healthy able-bodied or tetraplegia, but peak thrombin generation is reduced in tetraplegic men receiving oral melatonin.

scholarly journals Characterization of the thrombin generation profile in systemic lupus erythematosus

2017 ◽  
Vol 104 (1) ◽  
pp. 35-41 ◽  
Author(s):  
A Kern ◽  
E Barabás ◽  
A Balog ◽  
Sz Burcsár ◽  
M Kiszelák ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Thrombin Generation ◽  
Area Under The Curve ◽  
Autoimmune Disorder ◽  
Systemic Lupus ◽  
Time To Peak ◽  
Cat Assay ◽  
Coagulation Tests ◽  
Healthy Control

Systemic lupus erythematosus (SLE) is a multisystemic inflammatory autoimmune disorder. Thrombotic events occur at a higher incidence among SLE patients. The investigation of thrombin generation (TG) with calibrated automated thrombogram (CAT) test as a global hemostasis assay is applicable for the overall functional assessment of the hemostasis. The aim of this study was to characterize the hemostatic alterations observed in SLE by CAT assay. In this study, CAT parameters and basic coagulation parameters of SLE patients (n = 22) and healthy control subjects (n = 34) were compared. CAT area under the curve (i.e., endogenous thrombin potential) was lower than normal in SLE (807 vs. 1,159 nM*min, respectively), whereas other CAT parameters (peak, lag time, time to peak, and velocity index) and the basic coagulation tests were within the normal range. The presence of anti-phospholipid antibodies and the applied therapy was not associated with hemostasis parameters in SLE. We concluded that the reported high risk of thrombosis is not related to TG potential.

scholarly journals Zinc deficiency may play a crucial role in dialysis-associated bacterial infections

2020 ◽  
Vol 11 (1) ◽  
pp. e9-e9
Author(s):  
Zahra Lotfi ◽  
Abbas Ali Zeraati ◽  
Elaheh Dashti ◽  
Tina Zeraati ◽  
Maryam Arghiany ◽  
...  
Keyword(s):  
Zinc Deficiency ◽  
Bacterial Infections ◽  
Critical Role ◽  
Serum Zinc ◽  
Zinc Level ◽  
Healthy Individuals ◽  
Mortality And Morbidity ◽  
Increased Risk ◽  
The Mean

Introduction: Systemic bacterial infections are a common cause of mortality and morbidity in hemodialysis patients. Zinc has a critical role in several immune system functions. Patients who have enough amounts of zinc are able to better face infections caused by various pathogens in comparison to those with zinc insufficiency Objective We sought to assess the role of zinc deficiency in dialysis-associated bacterial infections. Patients and Methods: Eighty-Three adult patients with end-stage renal disease (ESRD) on hemodialysis including 43 patients with bacterial infectious complications and 40 non-infected patients as well as 41 healthy individuals were enrolled. Clinical data, laboratory values including serum zinc level and imaging findings were collected. SPSS was utilized to analyze the data with a significance cutoff set at P < 0.05. Results: Out of 124 participants, 80 (64.51%) were males and 44 (35.49%) were females. The mean age of infected hemodialysis group, non-infected hemodialysis group, and healthy controls were 50.8 ± 16.25, 49.1 ± 18.1, and 56.3 ± 18.2 years, respectively. Catheter site infection (37.3%) and urinary tract infection (30.2%) were the most common infections. The mean serum zinc concentration was significantly lower in the infected patients, compared to non-infected patients and healthy individuals (P < 0.001). Conclusion: The ESRD patients on hemodialysis have lower serum zinc levels which are associated with increased risk of bacterial infection. The role of screening for zinc deficiency and use of supplemental zinc in these patients need to be studied.

scholarly journals THE ROLE OF INTERLEUKIN 1β GENE POLYMORPHISM IN DEVELOPMENT OF PREDOMINANTY SENSORY CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY

2019 ◽  
Vol 21 (1) ◽  
pp. 141-148
Author(s):  
T. E. Popova ◽  
N. A. Shnayder ◽  
M. M. Petrova ◽  
A. A. Tappakhov
Keyword(s):  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Study Groups ◽  
Krasnoyarsk Region ◽  
Genotype Frequencies ◽  
Increased Risk ◽  
Significant Difference ◽  
Risk Of Disease ◽  
T Locus ◽  
Il1b Gene

The aim of the present study was a search for associations between the polymorphic allelic variants 3954 C>T (rs1143644) and -511C>T (rs16944) of IL1B gene in the patients with sensory predominant chronic inflammatory demyelinating polyneuropathies (SP-CIDP) from Krasnoyarsk Region and the Sakha (Yakutia) Republic. A total of 95 people were examined, having been divided into 2 groups according to their residence. The first group consisted of 42 patients living in the Sakha (Yakutia) Republic. The second group included 53 patients living in the Krasnoyarsk Region. It was revealed that the carriers of homozygous CC genotype in the 3954C>T locus were more often detected in patients from the Sakha (Yakutia) Republic, and the carriage of TT genotype is found exclusively in the patients from Krasnoyarsk Region. When comparing the different genotype frequencies in the -511CT locus, we did not reveal any statistically significant differences between the two groups of patients. Presence of the CC genotype of the 3954C>T locus was associated with a significantly increased risk of disease in the patients from Sakha (Yakutia) Republic, while carrying CT and TT genotypes at the locus 3954C>T and the TT genotype at the locus -511C>T, is associated with increased risk disorder among patients of the Krasnoyarsk Region. The frequency of carriage of various genotypes in the 3954C>T and -511C>T loci of the IL1B gene was prevalent among the patients from the Sakha (Yakutia) Republic, the association of genotypes of CC/CT prevailed in patients from the Krasnoyarsk Region (p = 0.005), as well as prevalence of CC/CC and CC/CT (p = 0.023). However, there was no statistically significant difference in occurrence of individual genotypes between the two study groups. When analyzing the carrier frequency of high-producing alleles of 3954C and -511C in patients with SP-CIDP, it was shown that they were significantly more common among patients from the Sakha (Yakutia) Republic and patients from the Krasnoyarsk Region than the low-producing 3954T and -511T alleles. Moreover, the 3954C allele was more often found in the Yakut group (p = 0.001), and in the -511C allele for the Krasnoyarsk group of patients (p = 0.05). The presence of 3954C and -511C alleles increases the risk of SP-CIDP development in patients from the Sakha (Yakutia) Republic, as well as carriage of 3954T allele in patients from the Krasnoyarsk Region.

Protein S levels modulate the activated protein C resistance phenotype induced by elevated prothrombin levels

2006 ◽  
Vol 95 (02) ◽  
pp. 236-242 ◽  
Author(s):  
Jeroen Brugge ◽  
Guido Tans ◽  
Jan Rosing ◽  
Elisabetta Castoldi
Keyword(s):  
Protein C ◽  
Thrombin Generation ◽  
Activated Protein C ◽  
Protein S ◽  
Healthy Individuals ◽  
Resistance Phenotype ◽  
Apc Resistance ◽  
Thrombosis Risk ◽  
Highly Correlated

SummaryElevated plasma prothrombin levels, due to the prothrombin 20210 G/A mutation or to acquired causes, area risk factor for venous thrombosis,partly because of prothrombin-mediated inhibition of the protein C anticoagulant pathway and consequent activated proteinC (APC) resistance. We determined the effect of plasma prothrombin concentration on the APC resistance phenotype and evaluated the role of protein S levels asa modulating variable. The effect of prothrombin and protein S levels on APC resistance was investigated in reconstituted plasma systems and in a population of healthy individuals using both the aPTT-based and the thrombin generation-based APC resistance tests. In reconstituted plasma, APC resistance increased at increasing prothrombin concentration in both assays. Enhanced APC resistance was caused by the effect of prothrombin on the clotting time in the absence of APC in the aPTT-based test, and on thrombin formation in the presence of APC in the thrombin generation-based test. In plasma from healthy individuals prothrombin levels were highly correlated to protein S levels. Since prothrombin and proteinS had opposite effects on the APC resistance phenotype, the prothrombin/protein S ratio was a better predictor of APC resistance than the levels of either protein alone. Prothrombin titrations in plasmas containing different amounts of proteinS confirmed that proteinS levels modulate the ability of prothrombin to induce APC resistance. These findings suggest that carriers of the prothrombin 20210 G/A mutation, who have a high prothrombin/protein S ratio, may experience a higher thrombosis risk than non-carriers with comparable prothrombin levels.

scholarly journals The Seasonal Variation of TKR Infection Rates

2017 ◽  
Vol 5 (5_suppl5) ◽  
pp. 2325967117S0016
Author(s):  
Ben Parkinson ◽  
Drew Armit ◽  
Michael Reid ◽  
Michelle Lorimer ◽  
Ian Harris
Keyword(s):  
Seasonal Variation ◽  
Surgical Site Infections ◽  
Study Groups ◽  
Winter Period ◽  
Infection Rates ◽  
Tropical Regions ◽  
Joint Registry ◽  
Increased Risk ◽  
Total Knee

Introduction: A seasonal variation in the incidence of surgical site infections has been described following a number of common surgical procedures. However in the setting of elective Total Knee Replacement (TKR), the role of environmental factors is an area of research that is currently lacking from the literature. Data recently presented from our institution demonstrates a possible trend toward higher infection rates during periods of increased temperature and humidity. The aim of this study was to investigate if seasonal and geographical factors influence the rate of TKR infection within Australia. Methods: Data from the AOA National Joint Registry for all primary TKRs performed within the last 5 years was analysed to determine the revision rates for early (<12 months) post-operative infection. The infection rates for tropical regions (Darwin, Cairns, Townsville, Mackay) were compared to the remainder of the country. A month-by-month analysis was performed to determine if there was a seasonal variation within the 2 study groups. Results: During the study period a total of 207,540 primary TKRs were performed (6,514 tropical vs 201,026 non-tropical regions). Overall, the rate of revision for infection was significantly higher for the tropical regions of Australia (0.80% vs 0.39%). In non-tropical regions, there was no observed seasonal variation of infection rates. In tropical regions, there was a clear seasonal variation found, with the winter months being associated with a significantly lower rate of infection than the remainder of the year (0.37% vs 0.94%). The infection rates were not significantly different between tropical (0.37%) and non- tropical (0.38%) regions during the winter period. Conclusion: To the best of our knowledge, this is the first study to investigate and demonstrate a significant influence from seasonal variation on primary TKR infection rates. This phenomenon is evident only within tropical regions, with the periods of warmer and humid weather resulting in a significantly increased risk of primary TKR infection. These findings require further investigation and research.

scholarly journals Whole blood thrombin generation in Bmal1-deficient mice

2014 ◽  
Vol 112 (08) ◽  
pp. 271-275 ◽  
Author(s):  
Marisa Ninivaggi ◽  
Hilde Kelchtermans ◽  
Marijke J. Kuijpers ◽  
Bianca Hemmeryckx ◽  
Johan W. M. Heemskerk ◽  
...  
Keyword(s):  
Whole Blood ◽  
Thrombin Generation ◽  
Peak Height ◽  
Premature Aging ◽  
Specific Substrate ◽  
Mouse Blood ◽  
Time To Peak ◽  
Cat Assay ◽  
Small Aliquot ◽  
Deficient Mice

SummaryThe Calibrated Automated Thrombogram (CAT) assay that measures thrombin generation (TG) in platelet-poor and -rich plasma, is increasingly being recognised as a more sensitive tool to determine the overall function of the haemostatic system. We developed a method enabling the measurement of TG in a small aliquot of blood. The objective was to validate this assay in mouse blood and to examine the rate and extent of TG in a mouse model of premature aging. TG was assayed in blood from 20– to 28-week-old brain and muscle ARNT-like protein-1 (Bmal1)-deficient (knockout, KO) mice and wild-type (WT) littermates. Bmal1-KO mice are known to display symptoms of premature aging. TG was initiated by adding calcium, tissue factor and a thrombin specific substrate. After TG, the samples were prepared for scanning electron microscopy (SEM). The intra-assay variations (%) in mouse blood of the endogenous thrombin potential (ETP), peak height, lag time, time-to-peak and velocity index were 10% or less (n=24). We found that Bmal1-KO mice have a significantly (p<0.001) higher ETP (437 ± 7 nM.min; mean ± SD, n=7) when compared with WT mice (ETP=220 ± 45 nM.min; mean ± SD, n=5). The peak heights also differed significantly (p=0.027). By applying SEM we found that Bmal1 deficient mice display a denser fibrin network with smaller pores compared to WT mice. In conclusion, the whole blood TG assay in mice revealed to be reproducible. As a proof-of-principle we have shown that the whole blood TG assay is capable of detecting a prothrombotic phenotype in Bmal1-KO mice.

scholarly journals Validation of the Role of Thrombin Generation Potential by a Fully Automated System in the Identification of Breast Cancer Patients at High Risk of Disease Recurrence

TH Open ◽  
2021 ◽  
Vol 05 (01) ◽  
pp. e56-e65
Author(s):  
Marina Marchetti ◽  
Patricia Gomez-Rosas ◽  
Marina Pesenti ◽  
Cristina Verzeroli ◽  
Cinzia Giaccherini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Thrombin Generation ◽  
Multivariable Analysis ◽  
Disease Recurrence ◽  
Automated System ◽  
Breast Cancer Patients ◽  
Cat Assay ◽  
Risk Categories

Abstract Background The measurement of thrombin generation (TG) potential by the calibrated automated thrombogram (CAT) assay provides a strong contribution in identifying patients at high risk of early disease recurrence (E-DR). However, CAT assay still needs standardization and clinical validation. Objective In this study, we aimed to validate the role of TG for E-DR prediction by means of the fully automated ST Genesia system. Methods A prospective cohort of 522 patients from the HYPERCAN study with newly diagnosed resected high-risk breast cancer was included. Fifty-two healthy women acted as controls. Plasma samples were tested for protein C, free-protein S, and TG by ST Genesia by using the STG-ThromboScreen reagent with and without thrombomodulin (TM). Results In the absence of TM, patients showed significantly higher peak and ETP compared with controls. In the presence of TM, significantly lower inhibition of ETP and Peak were observed in patients compared with controls. E-DR occurred in 28 patients; these patients had significantly higher peak and endogenous thrombin potential (ETP) in the absence of TM compared with disease-free patients. Multivariable analysis identified mastectomy, luminal B HER2-neg, triple negative subtypes, and ETP as independent risk factors for E-DR. These variables were combined to generate a risk assessment score, able to stratify patients in three-risk categories. The E-DR rates were 0, 4.7, and 13.5% in the low-, intermediate-, and high-risk categories (hazard ratio = 8.7; p < 0.05, low vs. high risk). Conclusion Our data validate the ETP parameter with a fully automated standardized system and confirm its significant contribution in identifying high-risk early breast cancer at risk for E-DR during chemotherapy.

scholarly journals Role of a thrombin generation assay in the prediction of infection severity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Boaz Elad ◽  
Gilat Avraham ◽  
Naama Schwartz ◽  
Adi Elias ◽  
Mazen Elias
Keyword(s):  
Hospital Mortality ◽  
Thrombin Generation ◽  
Systemic Infection ◽  
Lag Time ◽  
Peak Height ◽  
Clinical Tool ◽  
Time To Peak ◽  
Thrombin Generation Assay ◽  
Failure Assessment

AbstractThrombin plays a central role in sepsis pathophysiology. The correlation of thrombin generation (TG) assays with infection severity and prognosis, and whether it can be used as a clinical tool, have been poorly explored and are the subjects of our research. We recruited 130 patients with systemic infection between 2016 and 2019. Patients were divided according to infection severity by using the sequential organ failure assessment (SOFA) and quickSOFA (qSOFA) scores. The hemostatic state was analyzed by Calibrated Automated Thrombogram. The primary end points were TG values and the secondary end point was in-hospital mortality. Patients with qSOFA ≥ 2 had a longer lag time (5.6 vs. 4.6 min) and time to peak (8 vs. 6.9 min) than those with lower scores (p = 0.014 and 0.01, respectively). SOFA ≥ 2 had a longer lag time (5.2 vs. 4.3 min), time to peak (7.5 vs. 6.7 min) and lower endogenous thrombin potential (ETP) (1834 vs. 2015 nM*min), p = 0.008, 0.019, and 0.048, respectively. Patients who died (11) had lower ETP (1648 vs. 1928 nM*min) and peak height (284 vs. 345 nM), p = 0.034 and 0.012, respectively. In conclusion TG assays may be a valuable tool in predicting infection severity and prognosis.

Thrombin Generation Measured Ex Vivo Following Microvasculor Injury Is Increased in SLE Patients with Antiphospholipid-protein Antibodies

1997 ◽  
Vol 78 (04) ◽  
pp. 1173-1177 ◽  
Author(s):  
Jacek Musiał ◽  
Jakub Swadźba ◽  
Miłosz Jankowski ◽  
Marek Grzywacz ◽  
Stanisława Bazan-Socha ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Thrombin Generation ◽  
Ex Vivo ◽  
Skin Incision ◽  
Anticardiolipin Antibodies ◽  
Small Blood Vessel ◽  
Anionic Phospholipids ◽  
Increased Risk ◽  
High Concentrations

SummaryAntiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and (β2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. However, the pathogenic mechanism leading to thrombosis in patients with APA remains unclear. We studied 32 patients with systemic lupus erythematosus (SLE) who were divided into two groups depending on the presence (n = 19) or absence (n = 13) of APA. Healthy volunteers (n = 12) matched by age and sex served as controls. In all subjects LA and IgG class anticardiolipin antibodies (ACA) were determined. Thrombin generation was monitored ex vivo measuring fibrinopeptide A (FPA) and prothrombin fragment F1 + 2 (F1 + 2) in blood emerging from a skin microvasculature injury, collected at 30 second intervals. In subjects with antiphospholipid antibodies mean FPA and F1 + 2 concentrations were signiF1cantly higher at most blood sampling times than in controls. In some SLE patients with APA the process of thrombin generation was clearly disturbed and very high concentrations of F1brinopeptide A were detected already in the F1rst samples collected. Two minutes after skin incision SLE patients without APA produced slightly more FPA, but not F1 + 2, as compared to healthy subjects. Mathematical model applied to analyze the thrombin generation kinetics revealed that APA patients generated signiF1cantly greater amounts of thrombin than healthy controls (p = 0.02 for either marker). In contrast, in the same patients generation of thrombin in recalciF1ed plasma in vitro was delayed pointing to the role of endothelium in the phenomenon studied. In summary, these data show for the F1rst time that in SLE patients with antiphospholipid-protein antibodies thrombin generation after small blood vessel injury is markedly increased. Enhanced thrombin generation might explain thrombotic tendency observed in these patients.

Vitamin A: dietologist’s position

2020 ◽  
pp. 49-57
Author(s):  
S. V. Orlova ◽  
E. A. Nikitina ◽  
L. I. Karushina ◽  
Yu. A. Pigaryova ◽  
O. E. Pronina
Keyword(s):  
Immune Response ◽  
Urinary Tract ◽  
Gastrointestinal Tract ◽  
Vitamin A ◽  
Developed Countries ◽  
Therapeutic Practice ◽  
The Past ◽  
Increased Risk ◽  
Mucous Membranes

Vitamin A (retinol) is one of the key elements for regulating the immune response and controls the division and differentiation of epithelial cells of the mucous membranes of the bronchopulmonary system, gastrointestinal tract, urinary tract, eyes, etc. Its significance in the context of the COVID‑19 pandemic is difficult to overestimate. However, a number of studies conducted in the past have associated the additional intake of vitamin A with an increased risk of developing cancer, as a result of which vitamin A was practically excluded from therapeutic practice in developed countries. Our review highlights the role of vitamin A in maintaining human health and the latest data on its effect on the development mechanisms of somatic pathology.

Sign in / Sign up

Export Citation Format

Share Document