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C0348 The role of plasma D-dimer testing in diagnosis of patients suspected to atrial source thrombi
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Abstracts / Thrombosis Research 130 (2012) S100–S202
high-risk population such as acute coronary syndrome (ACS) patients.For this purpose, we have investigated the possible association between systemic atherosclerotic burden, measured by intima-media thickness (IMT) and pulse wave velocity (PWv) at common carotids (cIMT and c-PWv) and femoral arteries (f-IMT and f-PWv), ankle brachial index (ABI), and Hcy plasma levels, in patients with ACS. Methods: Study population consisted of 101 patients [M= 71; F = 30; age 64 (37–91) y.o.] with previous (1 year) ACS. Cardiovascular risk factors (CRFs) were assessed in each subject, according to current guidelines. All patients, clinically stable and in good psychophysical conditions, underwent clinical examination, blood sampling, ECG at rest, ultrasound (US) assessment and ABI. Hcy values were assessed in the absence of any vitamin supplementation. Results: c-IMTN 0.9 mm and f-IMT N 1.2 mm were found in 42.6% and 39.6% patients, respectively; 32.7% patients presented ABI b 0.9; c-PWv and f-PWv impairment was found in 23.8% and 27.7% patients, respectively.Hcy median values were 11.65 (1.6-24.6) μmol/L; Hcy values N15 μmol/L were found in 33.7% patients.Significant associations between Hcy values and markers of atherosclerotic burden and peripheral arterial diseases were confirmed by correlations (Hcy and: f-IMT, r = 0.315, p = 0.003; c-PWv, r = 0.453, p b 0.0001; f-PWv, r = 0.366, p b 0.0001, ABI, r = −0.375, p b 0.0001) and data distributions [f-IMT, c-PWv, f-PWv, ABI values according to Hcy cut-off (15 μmol/L), p values: 0.042, b0.0001, 0.002, 0.009, b0.0001, respectively].In hyperhomocysteinemic patients, c-IMT N 0.9 mm and f-IMT N 1.2 mm occurred in 56.3% and 56.3%, in comparison to 36.1% and 32.8% of patients with normal Hcy value (p= 0.062, p = 0.029, respectively); no significant difference according to presence of CRFs was found. Impairment of ABI occurred in 63.3% hyperhomocysteinemic patients, in comparison to 25.9% of patients with normal Hcy value (p= 0.001) Comment: In high-risk population, Hcy value assessment may represent a useful marker, over traditional risk factors, in order to detect patients with an increased systemic atherosclerotic burden. doi:10.1016/j.thromres.2012.08.032
C0316 Effects of hemodynamic forces on tissue factor RNA expression in human endothelial cells Bauer Sumpio Yale UniversityVascular Surgery - 333 Cedar St., New Haven, CT, USA 06510 Background: Atherosclerotic lesions predominantly localize in areas exposed to distinct hemodynamic conditions. In such lesions, tissue factor (TF) is over-expressed. Therefore, we hypothesized that varying types of mechanical forces may induce different effects on TF expression in endothelial cell, and may also influence the effects of chemical stimuli. Methods: TF RNA expression in HUVEC exposed to mechanical stress in the presence or absence of chemical stimulation with thrombin (Th) was determined. The forces examined were: steady unidirectional laminar flow (LF), pulsatile unidirectional laminar flow (PF), constant oscillatory flow (OF), pulsatile to-fro flow (TFF) and cyclic strain (CS). Results: Mechanical stimulation of HUVEC with LF for 2 hours induced an 8.7 ± 0.7fold increase in TF RNA expression, while PF induced 4.7 ± 0.9and TFF induced 8.6 ± 1.7 fold, respectively. These responses were significantly higher than static controls. Exposure to OF or CS did not result in any significant increase, whereas chemical stimulation with Th led to significant TF expression (4.9 ± 0.3 fold). The combination of mechanical–chemical stimuli induced significantly higher TF expression than mechanical stresses alone, and this effect was synergistic. Combination of LF+ Th for 2 hours induced significantly increased TF expression (16.6 ± 1.7 fold), as did PF+ Th (14.8 ± 2.4) and TFF + Th
(17.4 ± 1.0). Furthermore, after 6 hours exposure, only TFF demonstrated significantly higher TF expression both with and without Th. Comment: While uniform laminar flow resulted in transient TF expression, disturbed flow induced sustained amplification of TF expression. Further investigation is needed to elucidate the mechanism of localized atherosclerosis in areas exposed to disturbed flow. doi:10.1016/j.thromres.2012.08.033
C0348 The role of plasma D-dimer testing in diagnosis of patients suspected to atrial source thrombi Irina Sazonova1, Uzoma Ibebuogu2, Inna Gladysheva2, Nikhil Kadle1, Gyanendra Sharma1, Ramon Figueroa1, Vincent Robinson1 1 Georgia Health Sciences University, Medicine - 1120 15th street, CB2609, Augusta GA, 30912, USA; 2University of Tennessee Health Sciences Center, Medicine - 956 Court Ave., Memphis, TN 38163, USA Background: Transesophageal echocardiography (TEE) is the accepted standard to diagnose cardiogenic thromboemboli that commonly applied to patients with atrial fibrillation and ischemic stroke. To minimize costs and risks of TEE we evaluated the usefulness of a Ddimer test as a supplemental work-up procedure for patients with suspected atrial source thrombi. Methods: Blood samples were collected from 49 patients with mean age 63± 14 years (56% males, 63% white) who clinically suspected to intra-cardiac thrombi. TEE was requested for indications including: ischemic stroke (48%), atrial fibrillation and flutter (52%). D-Dimer levels were assessed by Latex assay. One-way Anova and Pearson test were used for statistical analysis. Results: The only clinical and demographic predictors that correlated with elevated D-dimer levels were presence of atrial fibrillation or flutter (P=0.016; r=0.3453) and advanced age (P=0.013; r=0.356). Patients with confirmed intra-cardiac clot had lower mean left atrial appendage velocity (23.7±8.4 cm/sec, pb 0.05) as compared to non-cardioembolic stroke (50.0±27.6 cm/sec) or no clot patients (42.5±23.7 cm/sec). Due to low positive prediction value and high variability, D-Dimer level was not statistically different between groups. At a cutoff value of b200 ng/ml, the fibrin D-dimer assay had a sensitivity, specificity, positive predictive value and negative predictive value of 100%, 19%, 15% and 100% respectively for the diagnosis of intracardiac clot. However, it was apparent that elevated D-dimer level (1877 ng/ml) has supported diagnosis of cardio-embolic stroke in a patient by MRI, despite negative CT angiography and TEE results. The D-dimer level of this patient was reduced to 218 ng/ml after 3 months of anticoagulation therapy. Comment: The gold standard for clot determination should not be limited to cardiac assessment with TEE and may be supplemented by D-dimer testing. The exclusion of intra-cardiac clot with TEE along does not eliminate the risk of prior thromboembolic events. doi:10.1016/j.thromres.2012.08.034
C0386 A meta-synthesis of qualitative studies exploring patients' and healthcare professionals views of atrial fibrillation and oral anticoagulant therapy Christian Borg Xuereb1, Rachel L. Shaw1, Gregory Y.H. Lip2, Deirdre A. Lane2 1 Aston University, School of Life and Health Sciences - Aston University, Birmingham, B4 7ET, UK; 2University of Birmingham, Centre for Cardiovascular Sciences - City Hospital, Birmingham, B18 7QH, UK
Abstracts / Thrombosis Research 130 (2012) S100–S202
high-risk population such as acute coronary syndrome (ACS) patients.For this purpose, we have investigated the possible association between systemic atherosclerotic burden, measured by intima-media thickness (IMT) and pulse wave velocity (PWv) at common carotids (cIMT and c-PWv) and femoral arteries (f-IMT and f-PWv), ankle brachial index (ABI), and Hcy plasma levels, in patients with ACS. Methods: Study population consisted of 101 patients [M= 71; F = 30; age 64 (37–91) y.o.] with previous (1 year) ACS. Cardiovascular risk factors (CRFs) were assessed in each subject, according to current guidelines. All patients, clinically stable and in good psychophysical conditions, underwent clinical examination, blood sampling, ECG at rest, ultrasound (US) assessment and ABI. Hcy values were assessed in the absence of any vitamin supplementation. Results: c-IMTN 0.9 mm and f-IMT N 1.2 mm were found in 42.6% and 39.6% patients, respectively; 32.7% patients presented ABI b 0.9; c-PWv and f-PWv impairment was found in 23.8% and 27.7% patients, respectively.Hcy median values were 11.65 (1.6-24.6) μmol/L; Hcy values N15 μmol/L were found in 33.7% patients.Significant associations between Hcy values and markers of atherosclerotic burden and peripheral arterial diseases were confirmed by correlations (Hcy and: f-IMT, r = 0.315, p = 0.003; c-PWv, r = 0.453, p b 0.0001; f-PWv, r = 0.366, p b 0.0001, ABI, r = −0.375, p b 0.0001) and data distributions [f-IMT, c-PWv, f-PWv, ABI values according to Hcy cut-off (15 μmol/L), p values: 0.042, b0.0001, 0.002, 0.009, b0.0001, respectively].In hyperhomocysteinemic patients, c-IMT N 0.9 mm and f-IMT N 1.2 mm occurred in 56.3% and 56.3%, in comparison to 36.1% and 32.8% of patients with normal Hcy value (p= 0.062, p = 0.029, respectively); no significant difference according to presence of CRFs was found. Impairment of ABI occurred in 63.3% hyperhomocysteinemic patients, in comparison to 25.9% of patients with normal Hcy value (p= 0.001) Comment: In high-risk population, Hcy value assessment may represent a useful marker, over traditional risk factors, in order to detect patients with an increased systemic atherosclerotic burden. doi:10.1016/j.thromres.2012.08.032
C0316 Effects of hemodynamic forces on tissue factor RNA expression in human endothelial cells Bauer Sumpio Yale UniversityVascular Surgery - 333 Cedar St., New Haven, CT, USA 06510 Background: Atherosclerotic lesions predominantly localize in areas exposed to distinct hemodynamic conditions. In such lesions, tissue factor (TF) is over-expressed. Therefore, we hypothesized that varying types of mechanical forces may induce different effects on TF expression in endothelial cell, and may also influence the effects of chemical stimuli. Methods: TF RNA expression in HUVEC exposed to mechanical stress in the presence or absence of chemical stimulation with thrombin (Th) was determined. The forces examined were: steady unidirectional laminar flow (LF), pulsatile unidirectional laminar flow (PF), constant oscillatory flow (OF), pulsatile to-fro flow (TFF) and cyclic strain (CS). Results: Mechanical stimulation of HUVEC with LF for 2 hours induced an 8.7 ± 0.7fold increase in TF RNA expression, while PF induced 4.7 ± 0.9and TFF induced 8.6 ± 1.7 fold, respectively. These responses were significantly higher than static controls. Exposure to OF or CS did not result in any significant increase, whereas chemical stimulation with Th led to significant TF expression (4.9 ± 0.3 fold). The combination of mechanical–chemical stimuli induced significantly higher TF expression than mechanical stresses alone, and this effect was synergistic. Combination of LF+ Th for 2 hours induced significantly increased TF expression (16.6 ± 1.7 fold), as did PF+ Th (14.8 ± 2.4) and TFF + Th
(17.4 ± 1.0). Furthermore, after 6 hours exposure, only TFF demonstrated significantly higher TF expression both with and without Th. Comment: While uniform laminar flow resulted in transient TF expression, disturbed flow induced sustained amplification of TF expression. Further investigation is needed to elucidate the mechanism of localized atherosclerosis in areas exposed to disturbed flow. doi:10.1016/j.thromres.2012.08.033
C0348 The role of plasma D-dimer testing in diagnosis of patients suspected to atrial source thrombi Irina Sazonova1, Uzoma Ibebuogu2, Inna Gladysheva2, Nikhil Kadle1, Gyanendra Sharma1, Ramon Figueroa1, Vincent Robinson1 1 Georgia Health Sciences University, Medicine - 1120 15th street, CB2609, Augusta GA, 30912, USA; 2University of Tennessee Health Sciences Center, Medicine - 956 Court Ave., Memphis, TN 38163, USA Background: Transesophageal echocardiography (TEE) is the accepted standard to diagnose cardiogenic thromboemboli that commonly applied to patients with atrial fibrillation and ischemic stroke. To minimize costs and risks of TEE we evaluated the usefulness of a Ddimer test as a supplemental work-up procedure for patients with suspected atrial source thrombi. Methods: Blood samples were collected from 49 patients with mean age 63± 14 years (56% males, 63% white) who clinically suspected to intra-cardiac thrombi. TEE was requested for indications including: ischemic stroke (48%), atrial fibrillation and flutter (52%). D-Dimer levels were assessed by Latex assay. One-way Anova and Pearson test were used for statistical analysis. Results: The only clinical and demographic predictors that correlated with elevated D-dimer levels were presence of atrial fibrillation or flutter (P=0.016; r=0.3453) and advanced age (P=0.013; r=0.356). Patients with confirmed intra-cardiac clot had lower mean left atrial appendage velocity (23.7±8.4 cm/sec, pb 0.05) as compared to non-cardioembolic stroke (50.0±27.6 cm/sec) or no clot patients (42.5±23.7 cm/sec). Due to low positive prediction value and high variability, D-Dimer level was not statistically different between groups. At a cutoff value of b200 ng/ml, the fibrin D-dimer assay had a sensitivity, specificity, positive predictive value and negative predictive value of 100%, 19%, 15% and 100% respectively for the diagnosis of intracardiac clot. However, it was apparent that elevated D-dimer level (1877 ng/ml) has supported diagnosis of cardio-embolic stroke in a patient by MRI, despite negative CT angiography and TEE results. The D-dimer level of this patient was reduced to 218 ng/ml after 3 months of anticoagulation therapy. Comment: The gold standard for clot determination should not be limited to cardiac assessment with TEE and may be supplemented by D-dimer testing. The exclusion of intra-cardiac clot with TEE along does not eliminate the risk of prior thromboembolic events. doi:10.1016/j.thromres.2012.08.034
C0386 A meta-synthesis of qualitative studies exploring patients' and healthcare professionals views of atrial fibrillation and oral anticoagulant therapy Christian Borg Xuereb1, Rachel L. Shaw1, Gregory Y.H. Lip2, Deirdre A. Lane2 1 Aston University, School of Life and Health Sciences - Aston University, Birmingham, B4 7ET, UK; 2University of Birmingham, Centre for Cardiovascular Sciences - City Hospital, Birmingham, B18 7QH, UK