scholarly journals The Influence of Race on Plasma Thrombin Generation In Healthy Subjects In Singapore

2017 ◽  
Vol 24 (7) ◽  
pp. 1144-1147 ◽  
Author(s):  
Chuen Wen Tan ◽  
Wan Hui Wong ◽  
Chin Kimg Tan ◽  
Yiong Huak Chan ◽  
Hartirathpal Kaur ◽  
...  

Race is touted as an independent risk factor for venous thromboembolism (VTE), although the basis for this is varied and contentious. Comparison of plasma thrombin generation (TG) using calibrated automated thrombogram (CAT) across races offers a modality that objectively measures global hemostatic function to evaluate this influence. Direct comparative data across races are currently not available. Aim is to establish the influence of race on plasma TG. Sixty normal participants, matched for age and gender, equally representing 4 races—Caucasian, Chinese, Indian, and Malay—were recruited. Thrombin generation parameters (lag time, time to peak, peak, and endogenous thrombin potential [ETP]) in platelet-poor plasma were measured using CAT. The mean ETP (standard deviation) for the different races were Caucasians: 1338.18 (194.19) nM·min; Chinese, 1318.91 (108.90) nM·min; Indians, 1389.81 (182.61) nM·min; and Malays, 1436.21 (184.24) nM·min. Caucasians had the longest mean lag time of 2.59 ± 0.37 seconds; Indians had the highest mean peak of 284.22 ± 30.74 nM, and Malays had the longest mean time to peak of 5.47 ± 0.59 seconds. Analysis based on race did not demonstrate any significant difference for all TG parameters. The greatest mean difference of ETP between any 2 races (Malays and Chinese) was 117.30 nM·min (95% confidence interval: −45.86 to 280.46 nM·min) which was within the predefined limit of equivalence. In a cohort of healthy participants, TG mediated by plasma factors is not influenced by race and does not explain the reported racial differences in VTE incidence. For the 4 racial groups studied, the use of separate normal ranges for plasma TG might not be essential.

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 185-185
Author(s):  
Rachel McPherson ◽  
Barbara Resnick ◽  
Elizabeth Galik

Abstract Communication and interactions are an integral part of care in long-term care settings. Resident variables, such as race and gender, shape communication and interaction between staff and residents. The Quality of Interactions Schedule (QuIS) was developed to measure the quality of verbal and nonverbal interactions among nursing staff and older adults initially for those in acute care and later used as well in a variety of long term care settings. A quantified measurement of the quality of interactions between residents and staff was created to quantify the QuIS. The purpose of this study was to describe the gender and racial differences in scored quality of interactions. Data for the present study was based on baseline data from the Evidence Integration Triangle for Behavioral and Psychological Symptoms of Dementia (EIT-4-BPSD) implementation study. A total of 535 residents from 55 settings were included in the analyses. An analysis of covariance was conducted to determine a difference in QuIS scores between males and females while controlling for age. The second model tested for differences in QuIS scores between blacks and whites while controlling for age and gender. There was not a statistically significant difference in QuIS scores between male and female residents. There was a significant difference in QuIS scores between those who were black versus white, such that those who were black received more positive interactions from staff than those who were white. Future work should focus on a deeper examination of resident factors and staff factors that may influence these interactions.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Suju Wang ◽  
Wenyang Hao ◽  
Chunxiao Xu ◽  
Daofeng Ni ◽  
Zhiqiang Gao ◽  
...  

Objective(s). The purpose of this study was to explore the effectiveness of wideband acoustic immittance (WAI) in the diagnosis of otosclerosis by comparing the differences in the energy reflectance (ER) of WAI between patients with otosclerosis and age- and gender-matched normal hearing controls in the Chinese population. Methods. Twenty surgically confirmed otosclerotic ears were included in the otosclerotic group. The ER of WAI at ambient and peak pressures, resonance frequency, and 226-Hz tympanogram were collected prior to surgery using a Titan hearing test platform (Interacoustics A/S, Middelfart, Denmark). All diagnoses of otosclerosis in the tested ear were confirmed by surgery after the measurements. Thirteen normal adults (26 ears) who were age- and gender-matched with the otosclerotic patients were included as the control group. Results. At peak pressure, the ERs of otosclerotic patients were higher than those of the control group for frequencies less than 4,000Hz and were lower for frequencies greater than 4,000Hz. In addition, within the analyzed frequencies, the differences observed at 2,520Hz was statistically significant (p<0.05/16=0.003, Bonferroni corrected). At ambient pressure, the differences observed at 1,260 and 6,350Hz were statistically significant (p<0.05/16=0.003, Bonferroni corrected). Although the differences between the otosclerotic and control groups exhibited similar trends to those in studies implemented in Caucasian populations, the norms in the present study in the control group were different from those in the Caucasian populations, suggesting racial differences in WAI test results. Regarding the middle ear resonance frequency, no significant difference was observed between the two groups (P>0.05). Conclusion. WAI can provide valuable information for the diagnosis of otosclerosis in the Chinese population. Norms and diagnostic criteria corresponding to the patient’s racial group are necessary to improve the efficiency of WAI in the diagnosis of otosclerosis.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sarina Falcione ◽  
Gina Sykes ◽  
Joseph Kamtchum Tatuene ◽  
Danielle Munsterman ◽  
Twinkle Joy ◽  
...  

Background and Purpose: Thrombus formation is central to pathophysiology of stroke in patients with atrial fibrillation. Whether factors in plasma contribute to thrombus generation in patients with atrial fibrillation remains unclear. In this study we sought to determine whether plasma contributes to thrombin generation in patients with atrial fibrillation. Methods: There were 78 acute ischemic strokes with atrial fibrillation and 37 non-stroke controls. Plasma thrombin generation was measured by thrombin generation assay, resulting lag time, peak thrombin, time to peak and area under the curve was assessed. Thrombin generation capacity was compared in stroke patients with atrial fibrillation to non-stroke controls. The relationship to anticoagulation was assessed. In vitro, the effect of anticoagulation on plasma thrombin generation was determined. Results: Thrombin generation capacity was increased (shorter lag time and time to peak) in ischemic stroke patients with atrial fibrillation compared to non-stroke atrial-fibrillation controls (p<0.05 and p<0.01, respectively). Anticoagulation decreased plasma induced thrombin generation. Ischemic stroke patients with atrial fibrillation treated with anticoagulation (DOAC or warfarin) had lower plasma induced thrombin generation compared to atrial-fibrillation patients not on anticoagulation (p<0.05). Thrombin generation by plasma could be further reduced by DOAC in an in-vitro assay. Conclusions: Stroke patients with atrial fibrillation have a higher plasma induced thrombin generation compared to atrial fibrillation controls. Factors in plasma such as leukocyte derived tissue factor likely contribute to thrombus formation in patients with atrial fibrillation. As such, components in plasma may represent new targets to reduce thrombus formation and stroke risk in patients with atrial fibrillation.


2017 ◽  
Vol 6 (2) ◽  
pp. 89-99 ◽  
Author(s):  
Malin Nylander ◽  
Signe Frøssing ◽  
Caroline Kistorp ◽  
Jens Faber ◽  
Sven O Skouby

Polycystic ovary syndrome (PCOS) is associated with increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) in later life. We aimed to study the effect of liraglutide intervention on markers of VTE and CVD risk, in PCOS. In a double-blind, placebo-controlled, randomized trial, 72 overweight and/or insulin-resistant women with PCOS were randomized, in a 2:1 ratio, to liraglutide or placebo 1.8 mg/day. Endpoints included between-group difference in change (baseline to follow-up) in plasminogen activator inhibitor-1 levels and in thrombin generation test parameters: endogenous thrombin potential, peak thrombin concentration, lag time and time to peak. Mean weight loss was 5.2 kg (95% CI 3.0–7.5 kg, P < 0.001) in the liraglutide group compared with placebo. We detected no effect on endogenous thrombin potential in either group. In the liraglutide group, peak thrombin concentration decreased by 16.71 nmol/L (95% CI 2.32–31.11, P < 0.05) and lag time and time to peak increased by 0.13 min (95% CI 0.01–0.25, P < 0.05) and 0.38 min (95% CI 0.09–0.68, P < 0.05), respectively, but there were no between-group differences. There was a trend toward 12% (95% CI 0–23, P = 0.05) decreased plasminogen activator inhibitor-1 in the liraglutide group, and there was a trend toward 16% (95% CI −4 to 32, P = 0.10) reduction, compared with placebo. In overweight women with PCOS, liraglutide intervention caused an approximate 5% weight loss. In addition, liraglutide affected thrombin generation, although not significantly differently from placebo. A concomitant trend toward improved fibrinolysis indicates a possible reduction of the baseline thrombogenic potential. The findings point toward beneficial effects of liraglutide on markers of VTE and CVD risk, which should be further pursued in larger studies.


2019 ◽  
Vol 25 ◽  
pp. 107602961986349
Author(s):  
Feng Dong ◽  
Longhao Wang ◽  
Chengbin Wang

Pregnancy is a hypercoagulable state associated with an increased risk of venous thrombosis. Calibrated automated thrombogram (CAT) is a test to monitor the thrombin generation (TG), a laboratory marker of thrombosis risk, and increases during normal pregnancy, but it is still unclear whether TG is related to the use of insulin in pregnant women with gestational diabetes mellitus (GDM). We performed thrombin generation by CAT on 135 normal pregnant women, including 43 in first trimester, 32 in second trimester, 60 in third trimester, respectively; 68 pregnant women with GDM were also enrolled, 19 patients with GDM using insulin to control blood glucose and 49 patients control their blood glucose through diet and exercise with noninsulin treatment. The overall CAT parameters were calculated using descriptive statistics method with mean ± standard deviation. Mean endogenous thrombin potential, peak thrombin generation, and StartTail time increased significantly with the pregnancy. There was no significant difference in TG test parameters except StartTail time( P = .003) in insulin-treated GDM group when compared to those without insulin in the GDM group. The normal ranges for CAT parameters in pregnant women were determined. Thrombin generation increased significantly in first trimester and remains stable in second and third trimester. The use of insulin in patient with GDM did not affect thrombin generation test. Our study helps to establish the reference range of thrombin generation in Chinese normal pregnant population and provide more basis to predict the risk of thrombus complicating during pregnancy.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4029-4029
Author(s):  
Wolfgang Wegert ◽  
Manuela Krause ◽  
Inge Scharrer ◽  
Ulla Stumpf ◽  
Andreas Kurth ◽  
...  

Abstract The changes of tissue factor (TF) blood levels in patients undergoing major surgery has been reported presenting controversial data. Whether this TF is hemostatically active or if it interacts with other coagulation factors, e.g. FVIII, is still unclear, making thrombotic risk and complications assessment for even more difficult. We analyzed plasma samples from four male patients aged 27–55 with severe hemophilia A without inhibitory antibodies, undergoing total knee replacement, which all gave informed consent. Initial FVIII doses before intervention was 75–80 U/kg. Treatment following intervention was targeted at 100 % FVIII serum levels. None received heparin. No bleeding events occurred during the observation period. The samples were taken at these timepoints (TP): 1. before preoperative FVIII substitution, 2. at the time of first incision (intervention start), 3. at circulation arrest release + 90 s after prosthesis implantation, 4. final suture (intervention end), 5. 24 h and 6. 48 h after intervention to assay procedurally induced TF production. Coagulation analyses were carried out using a fluorometric thrombin generation assay (TGA) in platelet rich plasma (PRP), RoTEG (rotation thrombelastography) in whole blood and a TF ELISA for the plasma samples’ TF levels. Both clotting function tests were started using TF diluted 1:100.000 and calcium chloride 16,7 mM (final conc.). TGA parameters were ETP, PEAK (maximum thrombin generation velocity), TIME TO PEAK, LAG TIME. TGA parameters directly related to thrombin activity (ETP; PEAK) showed no change during the intervention, but a sharp decrease 24 h later with a partial recovery 48 h later. TGA time marks (TIME TO PEAK, LAG TIME) changed in an inverse way, except for the difference from LAG TIME and TIME TO PEAK, which shortened continously after circulation arrest removal. RoTEG was characterized using 4 parameters: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF) and clot formation rate (CFR). After preoperative FVIII substitution, CT decreased by 10 % and CFT by 50 % in 48 h. MCF stayed unchanged during the intervention and the following 24 h, but increased by 20 % at 48 h. CFR increased by 10 % during intervention, and by 20 % from 24 to 48 h. TF ELISA showed preoperative TF plasma levels from 11 to 271 pg/ml. After release of circulation arrest (TP 3) TF concentration increased sharply (4 times the initial value), which was not detectable in the samples taken at TPs 2 and 4. TF levels further increased at TPs 5 and 6 to 170 % and 317 % resp. Altogether, TF plasma levels elevated after major surgery seem to correspond to a potential risk factor for postoperative thrombosis, especially when elevation is induced after intervention. However, functional coagulation assays do not change uniformly, as the thrombin generation assay reflects no marked changes under intervention, but in the period after(24–48 h). Changes in the RoTEG whole blood clotting assay are not dramatic but indicate a thrombophilic shift in coagulation balance also pronouned at 24–48h, too. These results demonstrate that increased coagulability after orthopedic surgery detected using functional clotting assays correlates with increased TF levels, but further studies must be performed to prove this relation in healthy individuals.


2015 ◽  
Vol 114 (07) ◽  
pp. 78-86 ◽  
Author(s):  
Georges Jourdi ◽  
Virginie Siguret ◽  
Anne Céline Martin ◽  
Jean-Louis Golmard ◽  
Anne Godier ◽  
...  

SummaryRivaroxaban and apixaban are selective direct inhibitors of free and prothrombinase-bound factor Xa (FXa). Surprisingly prothrombin time (PT) is little sensitive to clinically relevant changes in drug concentration, especially with apixaban. To investigate this pharmacodynamic discrepancy we have compared the kinetics of FXa inhibition in strictly identical conditions (pH 7.48, 37 °C, 0.15 M). KI values of 0.74 ± 0.03 and 0.47 ± 0.02 nM and kon values of 7.3 ± 1.6 106 and 2.9 ± 0.6 107 M-1 s-1 were obtained for apixaban and rivaroxaban, respectively. To investigate if these constants rationalise the inhibitor pharmacodynamics, we used numerical integration to evaluate impact of FXa inhibition on thrombin generation assay (TGA) and PT. Simulation predicted that in TGA triggered with 20 pM tissue factor, 100 ng/ml apixaban or rivaroxaban increased 1.8– or 3.0-fold the lag time and 1.4– or 2.0-fold the time to peak, whilst decreasing 1.2– or 3.1-fold the maximum thrombin and 1.7– or 3.5-fold the endogenous thrombin potential. These numbers were consistent with those obtained through the corresponding TGA triggered in plasma spiked with apixaban or rivaroxaban. Simulated PT ratios were also consistent with the corresponding plasma PT: markedly less sensitive to apixaban than to rivaroxaban. Analogous differences in TGA and PT were obtained irrespective of the drug amount added. We concluded that kon values for FXa of apixaban and rivaroxaban rationalise the unexpected lower sensitivity of PT and TGA to the former.


2018 ◽  
Vol 3 (2) ◽  
pp. 57
Author(s):  
Fereshte Dehghan Banadaki ◽  
Mahboubeh Mansouri ◽  
Reza Shekarriz-Foumani

Introduction: Allergic diseases include a wide range of symptoms such as asthma, rhinitis, urticaria, eczema, and gastrointestinal symptoms that are becoming increasingly prevalent in today’s world. Exposure to food allergens is one of the contributing factors for allergic diseases in humans. The identification of susceptibility to food allergens plays an important role in the prevention and treatment of allergic diseases.Materials and Methods: After the clinical diagnosis of allergic diseases, patients were examined using the skin prick test.The method of collecting data was observational. All data were entered in SPSS software version 21 and analyzed using descriptive and inferential statistics.Results: A total of 466 patients with a mean age of                          years were studied, of which 58.6% were boys and 41.4% were girls. A total of 44.2% patients had asthma, 21.7% had allergic rhinitis, 2.1% had allergic sinusitis, 1.7% had conjunctivitis, 1.1% had angioedema, 11.6% had urticaria, 19.7% had eczema, and 26.8% had gastrointestinal allergic symptoms. A total of 114 patients (24.5%) had food allergies, of which 43.9% were girls and 56.1% were boys. In terms of the age and gender of patients, no statistically significant difference was observed between different food allergens (P<.05). The most common allergens in patients under study were peanuts (7.9%), milk (7.3%), almond (6.6%), freshwater fish (6.6%), and walnuts (6.4%).Conclusion: The findings revealed that allergen prevalence in each region is influenced by its climatic conditions, people’s food habits, their racial differences, and their lifestyles.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 718-718
Author(s):  
Romy Kremers ◽  
Stéphane Zuily ◽  
Hilde Kelchtermans ◽  
Tessa Peters ◽  
Saartje Bloemen ◽  
...  

Abstract Background: The antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies directed mainly against prothrombin and β2-glycoprotein I. The syndrome is associated with an increased risk of thrombosis. The global hemostatic state in a patient can be tested by measuring thrombin generation (TG). Recently, we developed a method to study the main pro- and anticoagulant processes at the basis of TG, called the thrombin dynamics method. Aim: In this study we investigated the dynamics of thrombin generation in healthy subjects and APS patients. Materials and methods: Healthy subjects (n=129) and antiphospholipid syndrome (APS) patients (n=31) were included in the study. Sixty-eight percent of the APS patients were lupus anticoagulant positive, anti-cardiolipin antibodies were detected in 84% of the patients, and 52% presented with anti-β2-glycoprotein I antibodies. Patients on anticoagulant therapy were excluded from the study. Thrombin generation was measured at 1 pM tissue factor (TF) and activated protein C (APC) system sensitivity was tested by measuring TG in the presence and absence of 20 nM thrombomodulin (TM). Results: Thrombin generation was measured in platelet poor plasma at 1 pM tissue factor. The lag time and time-to-peak were significantly prolonged in APS patients compared to healthy subjects (lag time: 3.30 ± 0.59 vs. 6.69 ± 4.26 min, p<0.001; time-to-peak: 8.33 ± 1.29 vs. 10.76 ± 4.51 min, p<0.001). The peak height was significantly higher in APS patients (240 ± 84 vs. 214 ± 58 nM, p<0.05) and the velocity index was elevated in APS patients (134 ± 66 vs. 70 ± 32 nM/min, p<0.001) compared to healthy subjects. The ETP values were comparable between healthy subjects and APS patients (1260 ± 235 vs. 1176 ± 362 nM*min). The pro- and anticoagulant processes underlying thrombin generation were studied separately. The total amount of prothrombin converted during thrombin generation (PCtot) did not differ between healthy subjects and patients (1234 vs. 1165 nM). However, the maximum rate of prothrombin conversion (PCmax) was significantly elevated in APS patients (291 vs 425 nM/min; p<0.001). The amount of thrombin-antithrombin (T-AT) complexes formed was comparable between patients and controls (1169 vs. 1098 nM), and the thrombin decay capacity (TDC) was comparable as well (0.675 vs. 0.674 min-1). These results are in line with the finding that the plasma levels of the main thrombin inhibitors are unchanged in APS patients. Antithrombin levels are on average 2.31 ± 0.44 μM in healthy subjects and 2.36 ± 0.56 μM in APS patients, and the mean α2-macroglobulin levels were 3.22 ± 0.77 μM in healthy subjects and 3.23 ± 1.11 μM in patients. Thrombomodulin reduced the ETP by 45% in healthy subjects, but had significantly less effect in APS patients (10%). The addition of TM decreased total prothrombin conversion by 40% and the maximum prothrombin conversion rate by 50% in healthy subjects. In patients, TM only slightly reduced total prothrombin conversion (8%) and the maximum prothrombin conversion rate (7%). Discussion: The thrombin generation results indicate a predisposition to thrombosis in APS patients, as the TG parameters peak height and the velocity index are increased. Examination of the underlying pro- and anticoagulant processes of prothrombin conversion and thrombin inactivation revealed that although the same amount of prothrombin is converted in patients, the maximum activity of the prothrombinase complex is higher, indicating that patients can generate thrombin faster. In addition, APS patients have a dysfunctional APC system, as prothrombin conversion and thrombin generation could be only slightly inhibited by the addition of thrombomodulin. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 119 (06) ◽  
pp. 899-905
Author(s):  
Stéphanie Roullet ◽  
Sylvie Labrouche ◽  
Geneviève Freyburger

Background During liver transplantation (LT), thrombin generation (TG) is altered. The most frequently used assay for TG is the Calibrated Automated Thrombogram (CAT). It is designed for series of plasmas and is semi-automated. Complete automation has led to a new device, the ST-Genesia, enabling quantitative standardized TG evaluation. Objective The aim of this observational study was to compare the TG results of the CAT and the ST-Genesia on frozen-thawed plasma samples prepared from the blood of LT patients. Patients and Methods Poor platelet plasma aliquots were prepared from blood samples from six LT patients selected to get the whole range of TG and were assessed with CAT (recombinant human tissue factor [TF] concentration 5 pm) and with ST-Genesia Bleedscreen assay (BS, using ‘low’ recombinant human TF concentration) and Thromboscreen assay (TS, using ‘medium’ recombinant human TF concentration). The TG parameters studied were: lag time, peak, time to peak, endogenous thrombin potential, velocity index and start tail. Results BS and TS did not differ significantly from each other whatever the parameter studied, whereas most of the CAT parameters were significantly different from those obtained with BS and TS. Hierarchical clustering analysis of the different parameters of TG showed three homogeneous groups. One cluster gathered TG quantitative parameters from ST-Genesia. A second cluster gathered all the kinetic parameters. The last cluster isolated the quantitative parameters of CAT. Conclusion In patients undergoing LT, TG performed with CAT and with ST-Genesia provided different results, for unknown reasons.


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