Assessment of endogenous fibrinolysis using a point-of-care assay to identify increased cardiovascular risk in patients with diabetes and ACS

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Kanji ◽  
Y.X Gue ◽  
D Dinarvand ◽  
M.Q Farag ◽  
D.A Gorog
Keyword(s):  
Whole Blood ◽  
Clinical Characteristics ◽  
Thrombus Formation ◽  
Point Of Care ◽  
Occlusion Time ◽  
Increased Risk ◽  
Significant Difference ◽  
Patients With Diabetes ◽  
Endogenous Fibrinolysis ◽  
Point Of Care Assay

Abstract Introduction Patients with diabetes mellitus (DM) are increased risk of myocardial infarction (MI) and following a MI, patients with DM have an increased risk of recurrent MI and cardiovascular (CV) death. Plasma turbidimetry studies show that hypofibrinolysis is a key abnormality in DM that may drive increased ischaemic risk. Such assays are cumbersome, require specialist expertise and do not provide information in a clinically-relevant timeframe. Assessment of fibrinolysis in whole blood, using a point-of-care assay, has revealed that in ACS patients, impaired fibrinolysis is predictive of adverse CV events. Whether this technique can identify residual risk in patients with DM, is unclear. Purpose It was our aim to compare thrombotic and endogenous fibrinolytic status between patients with and without DM, presenting with ACS. Methods We conducted a prospective, observational study of consecutive patients admitted with ACS. Venous blood was taken to assess thrombotic and thrombolytic status using the point-of-care Global Thrombosis Test, assessing time to occlusive thrombus formation under high shear (occlusion time, OT) and time taken for spontaneous lysis of the thrombus (lysis yime, LT). Blood was taken after dual antiplatelet therapy (DAPT) loading, but before administration of fondaparinux or low molecular weight heparin. Patients with renal or hepatic impairment, known bleeding diathesis, thrombocytopenia and those taking anticoagulation were excluded. Results A total of 775 patients were included, of whom 158 (20%) had DM. Patients with DM, compared to those without DM, more frequently had hypertension (70% vs. 39%, p<0.001), hyperlipidaemia (65% vs. 29%, p<0.001), higher BMI (28.6 [25.3–32.0] vs. 26.6 [23.7–29.8] kg/m2, p<0.001) and prior MI (28% vs 9%, p<0.001), but were less often smokers (23% vs. 34% p=0.007). In all other clinical characteristics DM and non-DM patients were matched. Time to occlusive thrombus formation was similar in patients with and without DM (OT 401 (284–519) s vs. 391 (289–514) s, p=0.603). There was a trend for longer LT in patients with DM compared to those without DM (LT 1634 (130–2321) s vs. 1562 (1247–2147) s, p=0.080). After propensity score matching to adjust for baseline differences in clinical characteristics, we observed a highly significant difference in LT between DM and non-DM patients (LT 1634 [1306–2321] s vs. 1387 [1109–1740] s, p<0.001). Patients with DM also had higher fibrinogen level (4.4 [3.5–5.4] vs. 4.1 [3.5–4.8] g/l, p=0.012) and higher C-reactive protein (5 [2–12] vs. 3 [1–8] mg/l, p=0.002). CRP correlated with LT (r=0.2, p=0.016), but no correlation was observed between fibrinogen and LT (r=0.069, p=0.424). Conclusions Amongst patients with ACS, those with DM exhibit markedly impaired endogenous fibrinolysis compared to those without DM, and this can be detected with a bedside assay using whole blood. This may explain the increased risk of secondary events in patients with ACS and DM. Funding Acknowledgement Type of funding source: None

scholarly journals Comparing Patient Characteristics, Clinical Outcomes, and Biomarkers of Severe Asthma Patients in Taiwan

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 764
Author(s):  
Shih-Lung Cheng ◽  
Kuo-Chin Chiu ◽  
Hsin-Kuo Ko ◽  
Diahn-Warng Perng ◽  
Hao-Chien Wang ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Clinical Characteristics ◽  
Linear Models ◽  
Patient Characteristics ◽  
Emergency Department Visits ◽  
Receiver Operating Characteristic Curves ◽  
Increased Risk ◽  
Significant Difference ◽  
Asthma Patients ◽  
Patients At Risk

Purpose: To understand the association between biomarkers and exacerbations of severe asthma in adult patients in Taiwan. Materials and Methods: Demographic, clinical characteristics and biomarkers were retrospectively collected from the medical charts of severe asthma patients in six hospitals in Taiwan. Exacerbations were defined as those requiring asthma-specific emergency department visits/hospitalizations, or systemic steroids. Enrolled patients were divided into: (1) those with no exacerbations (non-exacerbators) and (2) those with one or more exacerbations (exacerbators). Receiver operating characteristic curves were used to determine the optimal cut-off value for biomarkers. Generalized linear models evaluated the association between exacerbation and biomarkers. Results: 132 patients were enrolled in the study with 80 non-exacerbators and 52 exacerbators. There was no significant difference in demographic and clinical characteristics between the two groups. Exacerbators had significantly higher eosinophils (EOS) counts (367.8 ± 357.18 vs. 210.05 ± 175.24, p = 0.0043) compared to non-exacerbators. The optimal cut-off values were 292 for EOS counts and 19 for the Fractional exhaled Nitric Oxide (FeNO) measure. Patients with an EOS count ≥ 300 (RR = 1.88; 95% CI, 1.26–2.81; p = 0.002) or FeNO measure ≥ 20 (RR = 2.10; 95% CI, 1.05–4.18; p = 0.0356) had a significantly higher risk of exacerbation. Moreover, patients with both an EOS count ≥ 300 and FeNO measure ≥ 20 had a significantly higher risk of exacerbation than those with lower EOS count or lower FeNO measure (RR = 2.16; 95% CI, 1.47–3.18; p = < 0.0001). Conclusions: Higher EOS counts and FeNO measures were associated with increased risk of exacerbation. These biomarkers may help physicians identify patients at risk of exacerbations and personalize treatment for asthma patients.

scholarly journals Clinical Outcomes of Pulmonary Embolism in Mexican Patients With COVID-19

2021 ◽  
Vol 27 ◽  
pp. 107602962110089
Author(s):  
Luis O. Bobadilla-Rosado ◽  
Santiago Mier y Teran-Ellis ◽  
Gabriel Lopez-Pena ◽  
Javier E. Anaya-Ayala ◽  
Carlos A. Hinojosa
Keyword(s):  
Pulmonary Embolism ◽  
Clinical Outcomes ◽  
Mexico City ◽  
Clinical Characteristics ◽  
Anticoagulation Therapy ◽  
Coagulation Abnormalities ◽  
Survivor Group ◽  
Increased Risk ◽  
Tertiary Center ◽  
Significant Difference

Coagulation abnormalities have been reported in COVID-19 patients, which may lead to an increased risk of Pulmonary Embolism (PE). We aimed to describe the clinical characteristics and outcomes of COVID-19 patients diagnosed with PE during their hospital stay. We analyzed patients with PE and COVID-19 in a tertiary center in Mexico City from April to October of 2020. A total of 26 (100%) patients were diagnosed with Pulmonary Embolism and COVID-19. We observed that 14 (54%) patients were receiving either prophylactic or full anticoagulation therapy, before PE diagnosis. We found a significant difference in mortality between the group with less than 7 days (83%) and the group with more than 7 days (15%) in Intensive Care Unit ( P = .004); as well as a mean of 8 days for the mortality group compared with 20 days of hospitalization in the survivor group ( P = .003). In conclusion, there is an urgent need to review antithrombotic therapy in these patients in order to improve clinical outcomes and decrease hospital overload.

Development of a point-of-care assay system for high-sensitivity C-reactive protein in whole blood

2003 ◽  
Vol 332 (1-2) ◽  
pp. 51-59 ◽  
Author(s):  
Jae Soon Ahn ◽  
Sunga Choi ◽  
Sang Ho Jang ◽  
Hyuk Jae Chang ◽  
Jae Hoon Kim ◽  
...  
Keyword(s):  
Whole Blood ◽  
Point Of Care ◽  
High Sensitivity ◽  
Assay System ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Point Of Care Assay

Inflammation and thrombosis in diabetes

2011 ◽  
Vol 105 (S 06) ◽  
pp. S43-S54 ◽  
Author(s):  
Katharina Hess ◽  
Peter Grant
Keyword(s):  
Plaque Rupture ◽  
Thrombus Formation ◽  
Atherosclerotic Lesion ◽  
Coagulation Factors ◽  
Fibrin Clot ◽  
Thrombotic Risk ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Inflammatory State

SummaryPatients with diabetes mellitus are at increased risk of cardiovascular morbidity and mortality. Atherothrombosis, defined as atherosclerotic lesion disruption with superimposed thrombus formation, is the most common cause of death among these patients. Following plaque rupture, adherence of platelets is followed by local activation of coagulation, the formation of a cross-linked fibrin clot and the development of an occlusive platelet rich fibrin mesh. Patients with diabetes exhibit a thrombotic risk clustering which is composed of hyper-reactive platelets, up regulation of pro-thrombotic markers and suppression of fibrinolysis. These changes are mainly mediated by the presence of insulin resistance and dysglycaemia and an increased inflammatory state which directly affects platelet function, coagulation factors and clot structure. This prothrombotic state is related to increased cardiovascular risk and may account for the reduced response to antithrombotic therapeutic approaches, underpinning the need for adequate antithrombotic therapy in patients with diabetes to reduce their cardiovascular mortality.

Validation of a new point-of-care assay for determination of β-carotene concentration in bovine whole blood and plasma

2012 ◽  
pp. n/a-n/a ◽  
Author(s):  
Jens Raila ◽  
Francis Enjalbert ◽  
Ralf Mothes ◽  
Andrea Hurtienne ◽  
Florian J. Schweigert
Keyword(s):  
Whole Blood ◽  
Point Of Care ◽  
Β Carotene ◽  
Point Of Care Assay

P4744Patients with atrial fibrillation exhibit a systemic prothrombotic state attributable to impaired endogenous fibrinolysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y X Gue ◽  
N Spinthakis ◽  
V Markides ◽  
T Wong ◽  
D Gorog
Keyword(s):  
Atrial Fibrillation ◽  
Healthy Volunteers ◽  
Platelet Reactivity ◽  
Point Of Care ◽  
Venous Blood ◽  
Full Blood Count ◽  
Newly Diagnosed ◽  
Prothrombotic State ◽  
Occlusion Time ◽  
Endogenous Fibrinolysis

Abstract Background The association of atrial fibrillation (AF) with thromboembolic stroke due to stasis in the left atrium and left atrial appendage is well described. Whether AF is associated with a systemic prothrombotic state, detectable in peripheral blood, unclear. Previous studies have been inconsistent, with some very small previous studies (<30 patients each) variably indicating that patients with AF may have raised platelet reactivity and levels of antithrombin III, d-dimer, PAI-1 and t-PA-PAI complexes. These cumbersome laboratory tests of coagulation and fibrinolysis are not readily available in the clinical setting. Purpose It was our aim to compare, in peripheral venous blood, thrombotic and endogenous fibrinolytic profile of healthy volunteers and patients with newly diagnosed nonvalvular atrial fibrillation (NVAF), using a point-of-care technique. Methods In a prospective observational study, venous blood samples were taken from 98 healthy volunteers and 100 patients with newly diagnosed NVAF in the out-patient setting. Patients with newly diagnosed NVAF had venous blood tested before any treatment was initiated with aspirin or oral anticoagulation. Thrombotic status was assessed using the Global Thrombosis Test (GTT), a point-of-care test using native non-coagulated blood, assessed within 15 sec of blood withdrawal. The time to form an occlusive venous thrombus in native (non-citrated) blood, a measure of platelet reactivity (occlusion time, OT) and the time taken to spontaneous endogenous fibrinolysis to restore flow (lysis time, LT) were assessed. Results Basic blood tests (full blood count, renal and liver function, inflammatory markers) were normal in all subjects. The groups were matched for sex and race. Mean age of the healthy cohort was 34±8 years and patients 65±10 years. Endogenous fibrinolysis was markedly impaired in patients with NVAF compared to healthy individuals as shown by markedly prolonged LT (median 2015s [interquartile range IQR 1555–2507] vs. 1124s [IQR 919–1554], p<0.ehz745.11201). There was no difference in platelet reactivity between patients and normal volunteers (369s [IQR 308–445]vs 368s [IQR 309–441], p=0.704). Sensitivity analysis was performed on a subgroup matched for age, sex and race. LT remained significantly longer in patients with NVAF compared to controls (1569s [IQR 1499–2244] vs. 1219s [IQR 943–1560], p=0.03), with no difference in platelet reactivity (p=NS). Conclusion In the largest study to date and using a clinically-friendly automated point-of-care technique, we show that patients with NVAF exhibit a systemic prothrombotic state, attributable to significantly impaired endogenous fibrinolysis compared with healthy volunteers. Further studies are needed to see if this could become a screening test for the prothrombotic state in patients with NVAF. Acknowledgement/Funding None

scholarly journals Rapid Point-of-Care Assay of Enoxaparin Anticoagulant Efficacy in Whole Blood

10.3791/3852 ◽  
2012 ◽  
Author(s):  
Mario A. Inchiosa ◽  
Suryanarayana Pothula ◽  
Keshar Kubal ◽  
Vajubhai T. Sanchala ◽  
Iris Navarro
Keyword(s):  
Whole Blood ◽  
Point Of Care ◽  
Point Of Care Assay

Toward development of a point-of-care assay of enoxaparin anticoagulant activity in whole blood

2011 ◽  
Vol 32 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Mario A. Inchiosa ◽  
Suryanarayana Pothula ◽  
Keshar Kubal ◽  
Vajubhai T. Sanchala ◽  
Iris Navarro
Keyword(s):  
Whole Blood ◽  
Point Of Care ◽  
Anticoagulant Activity ◽  
Point Of Care Assay

scholarly journals Assessment of Bleeding Phenotype in Hemophilia Α By a Novel Point-of-Care Global Assay

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4662-4662
Author(s):  
Debnath Maji ◽  
Michael A Suster ◽  
Divyaswathi Citla Sridhar ◽  
Maria Alejandra Pereda ◽  
Janet Martin ◽  
...  
Keyword(s):  
Whole Blood ◽  
Research Funding ◽  
Thrombin Generation ◽  
Hemophilia A ◽  
Point Of Care ◽  
Blood Samples ◽  
Healthy Group ◽  
Significant Difference ◽  
Bleeding Score ◽  
Bleeding History

Introduction: Patients with Hemophilia A have considerable phenotypic heterogeneity with respect to clinical severity based on their baseline factor levels. As clinical bleeding risk is helpful to individualize factor replacement therapy in hemophilia patients, previous studies have utilized direct and indirect methods of thrombin generation to classify individual bleeding phenotypes, however, with variable results. An easy to use, point-of-care, global assay to assess bleed phenotype, can be a useful tool in the clinical setting to determine intensity of prophylaxis therapy for patients with hemophilia. We have previously introduced a novel, point-of-care (POC), dielectric microsensor, ClotChip, and demonstrated its sensitivity to factor replacement in patients with severe hemophilia A. We aim to further test the ability of ClotChip in assessment of a bleeding phenotype, as described by a bleeding score, in patients with hemophilia A. Methods: After IRB approval, 28 patients with hemophilia A of varying severity and well-characterized bleeding history, were enrolled in this study at the time of trough factor levels. The bleeding history was extracted from patient charts and included number of bleeds (joint and soft-tissue), annual factor usage in terms of units/kg, and number of target joints. These parameters were used to generate a bleeding score (range: 0 - 24), and patients were divided in to 2 categories with scores between 0 - 12 (n=14) and > 12 (n=14). Healthy volunteers (n=17) were accrued as controls. Whole blood samples were obtained by venipuncture into collection tubes containing 3.2% sodium citrate. Samples were then tested with the ClotChip within 2 hours of collection. ClotChip is based on the electrical technique of dielectric spectroscopy (DS) and features a low-cost (material cost < $1), small- sized (26mm × 9mm × 3mm), and disposable microfluidic biochip with miniscule sample volume (< 10 µL). The ClotChip readout was taken as the temporal variation in the real part of blood dielectric permittivity at 1 MHz. Our previous studies have shown that the ClotChip readout is sensitive to the global coagulation process and the time to reach a peak in permittivity (Tpeak) is a sensitive parameter to assess coagulation factor defects. Thrombin generation assay (TGA) using low tissue factor concentration was also performed on blood samples according to the manufacturer's direction. TGA was not available for 4 hemophilia and 2 control samples. Endogenous thrombin potential (ETP) parameter of TGA was used in this study to assess thrombin generation. Data are reported as mean ± standard deviation (SD). Analysis of variance (ANOVA) was used to test for statistical significance between groups with P < 0.05. Spearman's correlation test was used to derive correlation statistics. Results: ClotChip exhibited a mean Tpeak of 2186s ± 1560s for hemophilia patients in the group with higher bleeding scores (i.e. score >12), a mean Tpeak of 931s ± 496s for the group with lower bleeding scores (i.e. score <12) and a mean Tpeak of 441s ± 74s for the healthy group (Figure 1A). A significant difference in Tpeak was found between the group with higher bleeding scores compared to the group with lower bleeding scores (P = 0.002) as well as between higher bleeding scores and the healthy group (P < 0.0001). However, no significant difference in the TGA ETP parameter was detected between the groups with higher bleeding scores (mean ETP: 470 ± 814) and lower bleeding scores (mean ETP: 471 ± 897) (Figure 1B). ETP exhibited a statistical difference between the healthy group (mean ETP: 3462 ± 575) and both hemophilia groups (P < 0.0001). We also carried out studies to investigate the correlative power of the ClotChip Tpeak parameter to the TGA ETP parameter when including additional blood samples that were collected at various times during a hemophilia patient's prophylaxis regimen. The ClotChip Tpeak parameter exhibited strong negative correlation to the TGA ETP parameter (Spearman's rs= -0.73, P < 0.0001). Conclusions: Our studies suggest that a novel dielectric microsensor (ClotChip) could be useful in assessing bleeding phenotype in hemophilia A patients, allowing rapid assessment of hemostasis using a miniscule amount of whole blood (<10 µL) at the POC. Further studies are needed to determine if ClotChip data can be used to individualize prophylactic factor replacement regimens in hemophilia A patients. Disclosures Maji: XaTek, Inc: Patents & Royalties: 9,995,701. Suster:XaTek, Inc: Consultancy, Patents & Royalties: 9,995,701. Mohseni:XaTek, Inc: Consultancy, Patents & Royalties. Ahuja:XaTexk Inc.: Consultancy, Patents & Royalties, Research Funding; Rainbow Children's Foundation: Research Funding; Bayer: Consultancy; Biovertiv Sanofi: Consultancy; Genentech: Consultancy.

scholarly journals Treatment Outcomes of Clopidogrel in Patients With ACS and Diabetes Undergoing PCI-analysis of Beijing Medicare Database

2020 ◽  
Author(s):  
Weihao Wang ◽  
Xiaoxia Wang ◽  
Lina Zhang ◽  
Jie Zhang ◽  
Fuli Man ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Large Scale ◽  
Coronary Intervention ◽  
Chinese Patients ◽  
Increased Risk ◽  
Significant Difference ◽  
Patients With Diabetes ◽  
One Year ◽  
Medicare Database

Abstract Background There are several clinical trials that proved the efficacy of clopidogrel treatment for patients with percutaneous coronary intervention. There are few large-scale research to explore the mortality associated with different duration use of clopidogrel in patients with diabetes and ACS undergoing PCI in the Chinese population. Objectives The objective of this analysis was to determine the efficacy of long-term clopidogrel therapy(≥ 12 months) versus short-term use(< 12 months) in Chinese patients with diabetes after PCI. Methods Using the Beijing Medicare database provided by Beijing Medical Security Bureau. The Beijing Medicare database contains medical data of about 16 million people, including about 990,000 patients with diabetes and a history of taking antidiabetic medicines. Patients were divided into two groups, one group of 9,116 patients receiving consecutive clopidogrel for one year or more, and another group of 3290 patients receiving consecutive clopidogrel less than one year. The primary of this analysis was the risk of all-cause death, myocardial infarction and revascularization. Results In patients with diabetes after PCI, long-term clopidogrel treatment was associated with a reduced risk of all-cause death(HR, 0.57[95%CI, 0.49–0.67], P < 0.0001), myocardial infarction(HR, 0.79[95%CI, 0.68–0.93], P = 0.0035) and an increased risk of angina(HR, 1.18[95%CI, 1.10–1.27], P < 0.0001]) and revascularization(HR, 1.07[95%CI, 1.01–1.13], P = 0.02]). There was no significant difference in the incidence of all-cause re-hospitalization(P = 0.7529), diabetes-related re-hospitalization and cerebrovascular re-hospitalization. Conclusion The present study concluded that long-term dual anti-platelet therapy including clopidogrel and aspirin could decrease the risks of all-cause death, myocardial infarction. But it could increase the risks of angina and revascularization. Further studies should interpret the cause of this question.

Sign in / Sign up

Export Citation Format

Share Document