scholarly journals Total Thrombus-Formation Analysis System (T-TAS): Clinical Application of Quantitative Analysis of Thrombus Formation in Cardiovascular Disease

2019 ◽  
Vol 119 (10) ◽  
pp. 1554-1562 ◽  
Author(s):  
Koichi Kaikita ◽  
Kazuya Hosokawa ◽  
Jeffrey R. Dahlen ◽  
Kenichi Tsujita
Keyword(s):  
Quantitative Analysis ◽  
Cardiovascular Diseases ◽  
Whole Blood ◽  
Thrombus Formation ◽  
Pressure Curve ◽  
Therapeutic Effects ◽  
Antithrombotic Agents ◽  
Bleeding Events ◽  
Antithrombotic Effects ◽  
Analysis System

AbstractVarious antithrombotic agents are clinically used to inhibit the cascade of arterial or venous thrombosis in cardiovascular diseases. Dual antiplatelet therapy with aspirin and P2Y12 inhibitors is prescribed in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Direct oral anticoagulants (DOACs) are widely used for the prevention or treatment of thromboembolism in patients with atrial fibrillation (AF) and venous thromboembolism. However, there has been no definitive tool to simultaneously monitor the antithrombotic effects of these drugs. The Total Thrombus-Formation Analysis System (T-TAS), a microchip-based flow chamber system that mimics in vivo conditions for evaluating whole blood thrombogenicity, was developed for the quantitative analysis of thrombus formation in whole blood specimens. The utility of T-TAS has been evaluated in CAD patients treated with antiplatelet therapies. The T-TAS PL chip area under the flow pressure curve (AUC) accurately assesses primary hemostasis and is sensitive to the therapeutic effects of various antiplatelet therapies. In addition, low AUC results are a significant predictor of periprocedural bleeding events in CAD patients undergoing PCI. The T-TAS AR chip AUC result is useful for assessing the efficacy of DOACs and warfarin in AF patients undergoing catheter ablation, and it is also a potential independent predictor of periprocedural bleeding events and avoidance of thrombosis in patients having undergone total knee arthroplasty. In conclusion, T-TAS is a useful index for evaluating the total antithrombotic effects of combination antithrombotic agents in patients with various cardiovascular diseases.

scholarly journals Cardiovascular risk factors are associated with augmented thrombogenicity in healthy individuals: analysis using the Total Thrombus-formation Analysis System

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuu Oda ◽  
Takashi Ito ◽  
Yoichiro Yamada ◽  
Tadashi Koga ◽  
Tomoka Nagasato ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Healthy Volunteers ◽  
Cardiovascular Risk Factors ◽  
Whole Blood ◽  
Thrombus Formation ◽  
Reference Intervals ◽  
Blood Samples ◽  
Whole Blood Samples ◽  
Analysis System

Abstract Background Rupture of an atherosclerotic plaque and subsequent exposure of the subendothelial prothrombotic matrix to blood cause arterial thrombosis. Circulating platelets play an indispensable role in the growth of arterial thrombi partially owing to their unique ability to adhere to the subendothelial matrix and to aggregate to each other under flow conditions. Recently, the Total Thrombus-formation Analysis System (T-TAS) was developed for ex vivo analysis of the thrombogenic potential of whole blood samples under flow conditions. Despite the potential clinical utility of the T-TAS in assessing the risk for thrombosis and bleeding, reference intervals for T-TAS analysis in healthy individuals have not been determined. Methods In total, 122 whole blood samples were collected from healthy volunteers ranging in age from 25 to 45 years. T-TAS analysis and hematological, physiological, and lifestyle assessments were conducted in these subjects. Whole blood samples anticoagulated with hirudin were perfused into a collagen-coated microchip (PL chip). The time to 10 kPa and the area under the flow pressure curve up to 10 min (AUC10) were analyzed as representative variables for thrombogenic potential. Reference intervals, which were defined as 2.5–97.5 percentiles, were determined. Additionally, univariate and multivariate analyses were performed to identify factors associated with the AUC10 in the T-TAS. Results The time to 10 kPa and the AUC10 widely varied, even in healthy volunteers. The reference intervals were 1.50–4.02 min and 223.4–456.8, respectively, at a shear rate of 1500 s− 1. Univariate and multivariate analyses showed that platelet counts were most significantly associated with the AUC10 of the T-TAS. The presence of one or more cardiovascular risk factors of a high body mass index, a high pulse pressure, high fasting serum glucose levels, high low-density lipoprotein-cholesterol levels, a history of smoking, and no habitual exercise, had the second largest effect on the AUC10 of the T-TAS. Conclusions Healthy volunteers who had any cardiovascular risk factors showed augmented thrombogenicity, even in artificial uniform capillaries, compared with those without any risk factors in the T-TAS.

scholarly journals Total Thrombus-Formation Analysis System can Predict 1-Year Bleeding Events in Patients with Coronary Artery Disease

2020 ◽  
Vol 27 (3) ◽  
pp. 215-225 ◽  
Author(s):  
Tatsuro Mitsuse ◽  
Koichi Kaikita ◽  
Masanobu Ishii ◽  
Yu Oimatsu ◽  
Nobuhiro Nakanishi ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Thrombus Formation ◽  
Bleeding Events ◽  
Artery Disease ◽  
Analysis System

Abstract 12614: Total Thrombus Formation Analysis System Can Predict High Bleeding Risk in Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nobuhiro Nakanishi ◽  
Koichi Kaikita ◽  
Kenichi Tsujita
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Thrombus Formation ◽  
Academic Research ◽  
Bleeding Risk ◽  
Coronary Intervention ◽  
Bleeding Events ◽  
Percutaneous Coronary ◽  
Analysis System ◽  
Research Consortium ◽  
High Bleeding Risk

Introduction: Antithrombotic therapy is established for the treatment in various cardiovascular events, however, it has shown to increase the bleeding risk. Total Thrombus-formation Analysis System (T-TAS) is reported to be useful for evaluating thrombogenicity. Hypothesis: We examined whether T-TAS might predict 1-year bleeding risk in patients undergoing percutaneous coronary intervention (PCI). Methods: This was a retrospective, observational study at Kumamoto University Hospital between April 2017 and March 2019. Blood samples obtained on the day of PCI were used in T-TAS to compute the thrombus formation area under the curve (AUC) (AR10-AUC30, AUC for AR chip). We divided the study population into 2 groups according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) (182 patients in ARC-HBR positive, 118 in ARC-HBR negative). The primary endpoint was 1-year bleeding events that were defined by Bleeding Academic Research Consortium type2, 3, or 5. Results: The AR10-AUC30 levels were significantly lower in the ARC-HBR positive group than in the ARC-HBR negative group (median [interquartile range] 1568.1 [1258.5-1744.1] vs. 1723.1 [1567.0-1799.5], p<0.001). The combination of ARC-HBR and AR10-AUC30 could discriminate the bleeding risk, and improved predictive capacity compared with ARC-HBR by c-statistics and integrated discrimination improvement. In multivariate Cox hazards analyses, combining ARC-HBR and lower AR10-AUC30 levels were significantly associated with 1-year bleeding events. Decision curve analysis revealed that combining AR10-AUC30 with ARC-HBR ameliorated risk-prediction of bleeding events. Conclusions: The results highlighted that AR10-AUC30 could be a potentially useful marker for predicting high bleeding risk in patients undergoing PCI.

scholarly journals Evaluation of the Antithrombotic Effects of Rivaroxaban and Apixaban Using the Total Thrombus-Formation Analysis System®: In Vitro and Ex Vivo Studies

2016 ◽  
Vol 8 (12) ◽  
pp. 899-907 ◽  
Author(s):  
Hidekazu Sugihara ◽  
Yoshiaki Idemoto ◽  
Takashi Kuwano ◽  
Yoshihisa Nagata ◽  
Joji Morii ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Thrombus Formation ◽  
Antithrombotic Effects ◽  
Analysis System

Combined Dabigatran and Antiplatelet Agents Assessed by the Novel Microchip-Based Flow Chamber System

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1167-1167
Author(s):  
Kenichi Tanaka ◽  
Kazuya Hosokawa ◽  
Tomoko Ohnishi ◽  
Hisayo Sameshima ◽  
Takehiko Koide ◽  
...  
Keyword(s):  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Antiplatelet Agents ◽  
Lag Time ◽  
Flow Chamber ◽  
Chamber System ◽  
Shear Rates ◽  
Antithrombotic Effects ◽  
Flow Pressure

Abstract Abstract 1167 Evaluation of the overall antithrombotic activity of dabigatran in combination with antiplatelet agents is difficult because plasma-based clotting for dabigatran, and platelet aggregometry in anticoagulated blood are two separate tests which do not reflect physiological interactions between soluble factors and platelets. The use of a flow chamber could be more suitable in evaluating a flow-dependent platelet activation and coagulation responses. The aim of the current study was to comparatively evaluate antithrombotic effects of dabigatran in combination with dual antiplatelet therapy (aspirin plus P2Y12 blockade) using the microchip-based flow chamber (T-TAS, Fujimori Kogyo, Japan)(1), and thrombin generation (TG) assay (Thrombinoscope, Maastricht, the Netherlands)(2). After the local ethics committee approval, blood samples were obtained from consented 5 healthy volunteers in the tubes containing 3.2% sodium citrate. Whole blood samples were mixed with dabigatran (250, 500, 1000 nM), aspirin (100 nM) plus ARC-66096 (P2Y12 inhibitor, 1000 nM) at 25¡C for 10 min. Corn trypsin inhibitor (50 μg/ml) was used to prevent contact activation. The whole blood sample was perfused in the capillary pre-coated with collagen and thromboplastin at the shear rate of 240 or 600 s−1. The process of thrombus formation was monitored by flow pressure increases inside the capillary; (i) lag time before it reaches 10 kPa (T10), (ii) occlusion time (OT) is the lag time before it reaches 80 kPa as thrombus completely occludes the capillary, and (iii) AUC30 is an area under the flow pressure curve (under 80 kPa) after 30 min of perfusion. For TG assay, platelet-rich plasma (platelet count 150 × 103/μl) was prepared from citrated whole blood. TG was triggered by adding 20 μl of CaCl2-fluorogenic substrate buffer to 80 μl of the sample mixed with tissue factor (1 pM) in each well. The lag time (min), and peak thrombin concentration (nM) were evaluated. In the flow chamber, dabigatran inhibited white thrombus formation in a concentration dependent manner at shear rates of 240 and 600 s−1(Fig. 1). At 500 nM of dabigatran, OT was prolonged by ∼2-fold from the (non-treated) control at both shear rates. The combination of aspirin and AR-C66096 only weakly suppressed thrombus formation, but it enhanced the antithrombotic efficacy of dabigatran at both shear rates (Fig. 1). In TG measurements using platelet-rich plasma, dabigatran at 500 nM prolonged the by 3.17-fold, and reduced the peak by 57.6% compared to the untreated control (Table 1). Aspirin and AR-C66096 weakly prolonged the lag time without affecting the peak height. There were relatively small changes in these parameters when antiplatelet agents were combined with dabigatran (Table 1). Our results suggest that combined antithrombotic effects of dabigatran, aspirin, and P2Y12inhibition can be demonstrated in the whole blood using the flow chamber system compared without additional plasma preparation required for TG assay. The re-calcified whole blood was perfused at the shear rate of 240 s−1 or 600 s−1. Asp/AR-C=aspirin and AR-C66096 Table 1. Lag time (min) Peak (nM) Native Asp/AR-C Native Asp/AR-C Control 6.8 ± 0.8 9.4 ± 3.2 92.1 ± 23.7 91.2 ± 29.5 Dabi 250 nM 18.6 ± 5.4 21.1 ± 4.5 69.3 ± 20.6 52.2 ± 13.6 Dabi 500 nM 21.6 ± 5.3 26.2 ± 10.2 53.0 ± 5.8 47.8 ± 9.1 Dabi 1000 nM 30.2 ± 5.6 35.1 ± 6.3 23.0 ± 6.9 22.0 ± 8.4 Dabi=dabigatran, Native=no antiplatelet agents, Asp/AR-C=aspirin and AR-C66096 Disclosures: Hosokawa: Fujimori Kogyo: Employment. Ohnishi:Fujimori Kogyo: Employment. Sameshima:Fujimori Kogyo: Employment.

scholarly journals Anti-Platelet Properties of Phenolic and Nonpolar FractionsIsolated from Various Organs of Elaeagnus rhamnoides (L.) A. Nelson in Whole Blood

2021 ◽  
Vol 22 (6) ◽  
pp. 3282
Author(s):  
Bartosz Skalski ◽  
Joanna Rywaniak ◽  
Aleksandra Szustka ◽  
Jerzy Żuchowski ◽  
Anna Stochmal ◽  
...  
Keyword(s):  
Whole Blood ◽  
Thrombus Formation ◽  
Blood Platelets ◽  
Sea Buckthorn ◽  
Platelet Activity ◽  
Bioactive Substances ◽  
Reducing Conditions ◽  
Triterpenic Acids ◽  
Platelet Proteome ◽  
Analysis System

Sea buckthorn (Elaeagnus rhamnoides (L.) A. Nelson) is a shrub growing in coastal areas. Its organs contain a range of bioactive substances including vitamins, fatty acids, various micro and macro elements, as well as phenolic compounds. Numerous studies of sea buckthorn have found it to have anticancer, anti-ulcer, hepatoprotective, antibacterial, and antiviral properties. Some studies suggest that it also affects the hemostasis system. The aim of the study was to determine the effect of six polyphenols rich and triterpenic acids rich fractions (A–F), taken from various organs of sea buckthorn, on the activation of blood platelets using whole blood, and to assess the effect of the tested fractions on platelet proteins: fraction A (polyphenols rich fraction from fruits), fraction B (triterpenic acids rich fraction from fruits), fraction C (polyphenols rich fraction from leaves), fraction D (triterpenic acids rich fraction from leaves), fraction E (polyphenols rich fraction from twigs), and fraction F (triterpenic acids rich fraction from twigs). Hemostasis parameters were determined using flow cytometry and T-TAS (Total Thrombus-formation Analysis System). Additionally, electrophoresis was performed under reducing and non-reducing conditions. Although all tested fractions inhibit platelet activation, the greatest anti-platelet activity was demonstrated by fraction A, which was rich in flavonol glycosides. In addition, none of the tested fractions (A–F) caused any changes in the platelet proteome, and their anti-platelet potential is not dependent on the P2Y12 receptor.

scholarly journals The usefulness of total thrombus-formation analysis system for predicting high bleeding risk in coronary artery disease patients taking anticoagulants who underwent percutaneous coronary intervention

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Nakanishi ◽  
K Kaikita ◽  
T Mitsuse ◽  
K Tsujita
Keyword(s):  
Atrial Fibrillation ◽  
Coronary Artery Disease ◽  
Thrombus Formation ◽  
Bleeding Risk ◽  
Coronary Intervention ◽  
Bleeding Events ◽  
Percutaneous Coronary ◽  
Artery Disease ◽  
Analysis System ◽  
High Bleeding Risk

Abstract Background Although anticoagulants are widely used for prevention of cerebral infarction in patients with atrial fibrillation (AF), venous thrombosis, and valvular disease, it is possible that anticoagulants increase bleeding events in daily medical practices. Recently, we reported that the total thrombus-formation analysis system (T-TAS) was useful for evaluating bleeding risk in coronary artery disease (CAD) patients. Aim We examined whether T-TAS was practical for predicting bleeding risk in CAD patients taking anticoagulants who underwent percutaneous coronary intervention (PCI). Methods This study was the retrospective analysis of the 500 consecutive CAD patients who underwent PCI. Blood samples obtained on the day of PCI were used in T-TAS to compute the thrombus formation area under the curve (AUC) (AR10-AUC30, AUC for AR chip). We divided the total number of study patients into two groups according to the presence of anticoagulants; 53 CAD patients with triple therapy (TT) and 447 CAD patients with dual antiplatelet therapy (DAPT). We compared clinical characteristics and prognosis between the two groups. The primary endpoint was 1-year bleeding events that were defined by ISTH bleeding criteria. We excluded the CAD patients who underwent emergency PCI, and who were treated for hemodialysis. Results All patients took aspirin and clopidogrel, or aspirin and prasugrel at baseline. Compared to the patients with DAPT, the patients with TT had atrial fibrillation and history of stroke. The AR10-AUC30 levels were significantly lower in the patients with TT than the patients with DAPT (median [interquartile range] 1402.6 [1095.1–1609.8] vs. 1679.8 [1526.4–1783.3], p&lt;0.001). Thirty-five patients (7%) had bleeding events during follow-up [11 cases (20.8%) in the patients with TT, 24 cases (5.4%) in the patients with DAPT]. Kaplan-Meier curve analysis showed a worse 1-year bleeding event-free survival rate in the patients with TT compared with the patients with DAPT (p&lt;0.001). Receiver operating characteristic analysis showed that AR10-AUC30 levels significantly predicted bleeding events (AUC 0.653, 95% CI 0.555–0.751; p=0.003) and the cut-off point was 1586.4 by Youden index in the present study. In multivariate Cox hazards analysis, low AR10-AUC30 level (≤1586.4) (hazard ratio 2.99; 95% CI 1.46–6.11; p=0.003) and taking warfarin (hazard ratio 3.02; 95% CI 1.24–7.34; p=0.015) were significant predictors for 1-year bleeding events. Conclusions The present findings suggested that the AR10-AUC30 level determined by T-TAS could be a useful marker for predicting high bleeding risk in CAD patients taking anticoagulants who underwent PCI. Funding Acknowledgement Type of funding source: None

scholarly journals Antithrombogenic properties of Tulbaghia violacea aqueous leaf extracts: assessment of platelet activation and whole blood clotting kinetics

RSC Advances ◽  
2021 ◽  
Vol 11 (48) ◽  
pp. 30455-30464
Author(s):  
Lerato N. Madike ◽  
M. Pillay ◽  
Ketul C. Popat
Keyword(s):  
Cardiovascular Diseases ◽  
Platelet Activation ◽  
Plant Extracts ◽  
Whole Blood ◽  
Blood Clotting ◽  
Therapeutic Effects ◽  
Leaf Extracts ◽  
Wide Range

Tulbaghia violacea plant extracts have been investigated for their potential therapeutic effects in the management of various ailments, among which are cardiovascular diseases, due to the wide range of phytocompounds that the plant possesses.

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