In vivo assessment of dual-function submicron textured nitric oxide releasing catheters in a 7-day rabbit model.

Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. Herein, a dualfunction submicron textured nitric oxide (NO)-releasing catheter was developed. The hemocompatibility and antithrombotic activity of vascular catheters were evaluated in both 20 h in vitro blood loop and 7 d in vivo rabbit model. Surface characterization assessments via atomic force microscopy show the durability of the submicron pattern after incorporation of NO donor S-nitroso-N-acetylpenicillamine (SNAP). The SNAP-doped catheters exhibited prolonged and controlled NO release mimicking the levels released by endothelium. Fabricated catheters showed cytocompatibility when evaluated against BJ human fibroblast cell lines. After 20h in vitro evaluation of catheters in a blood loop, textured-NO catheters exhibited a 13-times reduction in surface thrombus formation compared to the control catheters, which had 83% of the total area covered by clots. After the 7 d in vivo rabbit model, analysis on the catheter surface was examined via scanning electron microscopy, where significant reduction of platelet adhesion, fibrin mesh, and thrombi can be observed on the NO-releasing textured surfaces. Moreover, compared to relative controls, a 63% reduction in the degree of thrombus formation within the jugular vein was observed. Decreased levels of fibrotic tissue decomposition on the jugular vein and reduced platelet adhesion and thrombus formation on the texture of the NO-releasing catheter surface are indications of mitigated foreign body response. This study demonstrated a biocompatible and robust dual-functioning textured NO PU catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. STATEMENT OF SIGNIFICANCE: Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. This study demonstrated a robust, biocompatible, dual-functioning textured nitric oxide (NO) polyurethane catheter in limiting fouling-induced complications for longer-term blood-contacting device applications. The fabricated catheters exhibited prolonged and controlled NO release that mimics endothelium levels. After the 7 d in vivo model, a significant reduction in platelet adhesion, fibrin mesh, and thrombi was observed on the NO-releasing textured catheters, along with decreased levels of fibrotic tissue decomposition on the jugular vein. Results illustrate that NO-textured catheter surface mitigates foreign body response.

Third trimester intrauterine fetal death: proposal for the assessment of the chronology of umbilical cord and placental thrombosis.

The timing of umbilical cord and placental thrombosis in the third trimester intrauterine fetal death (TT-IUFD) may be fundamental for medico-legal purposes, when it undergoes medical litigation due to the absence of risk factors. Authors apply to human TT-IUFD cases a protocol, which includes histochemistry and immunohistochemistry (IHC) for the assessment of thrombi's chronology. A total of 35 thrombi of umbilical cord and/or placenta were assessed: 2 in umbilical artery, 6 in umbilical vein, 15 in insertion, 10 in chorionic vessels, 1 in fetal renal vein, 1 in fetal brachiocephalic vein. Thrombi's features were evaluated with hematoxylin-eosin, Picro-Mallory, Von Kossa, Perls, and immunohistochemistry for CD15, CD68, CD31, CD61, and Smooth Muscle Actin. The estimation of the age of the thrombi was established by applying neutrophils/macrophages ratio taking into consideration, according to literature, the presence of hemosiderophagi, calcium deposition, and angiogenesis. To estimate an approximate age of fresh thrombi (< 1 day), a non-linear regression model was tested. Results were compared to maternal risk factors, fetal time of death estimated at autopsy, mechanism, and cause of death. Our study confirms that the maternal risk factors for fetal intrauterine death and the pathologies of the cord, followed by those of the placental parenchyma, are the conditions that are most frequently associated with the presence of thrombi. Results obtained with histological stainings document that the neutrophile/macrophage ratio is a useful tool for determining placental thrombi's age. Age estimation of thrombi on the first day is very challenging; therefore, the study presented suggests the N/M ratio as a parameter to be used, together with others, i.e., hemosiderophagi, calcium deposition, and angiogenesis, for thrombi's age determination, and hypothesizes that its usefulness regards particularly the first days when all other parameters are negative.

Assessment of Platelet Thrombus Formation under Flow Conditions in Adult Patients with COVID-19: An Observational Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation, which may dysregulate platelet function. Total Thrombus-Formation Analysis System (T-TAS) is a flow-chamber device that analyses platelet-mediated thrombus formation in capillary channels through the following parameters: (1) the area under the flow-pressure curve (AUC), (2) occlusion start time (OST), time needed to reach OST, and (3) occlusion time (OT), time needed to reach the occlusion pressure. METHODS AND FINDINGS: Sixty-one COVID-19 patients admitted to intensive, subintensive, and low intensive care were prospectively enrolled according to the time of admission: group A (up to 8 days) (n = 18); group B (from 9 to 21 days) (n = 19), and group C ( > 21 days) (n = 24). T-TAS measurements were performed at enrolment and after 7 days. Median OST was similar among groups. AUC was lower in group A compared to B (p = 0.001) and C (p = 0.033). OT was longer in group A compared to B (p = 0.001) and C (p = 0.028). Platelet count (PC) was higher in group B compared to A (p = 0.024). The linear regression showed that OT and AUC were independent from PC in group A (OT: 0.149 [95% confidence interval [CI]: -0.326 to 0.624], p = 0.513 and AUC: 0.005 [95% CI: -0.008 to 0.017], p = 0,447). In contrast, in group B, PC was associated with OT (-0.019 [-0.028 to 0.008], p = 0.023) and AUC (0.749 [0.358-1.139], p = 0,015), similarly to group C. Conversely, patients with different illness severity had similar T-TAS parameters. CONCLUSION: COVID-19 patients display an impaired platelet thrombus formation in the early phase of the disease compared to later stages and controls, independently from illness severity.

Anti-clogging mechanisms of a motion-activated chest tube patency maintenance system: Histology and high-speed camera assessment.

The motion-activated system (MAS) employs vibration to prevent intraluminal chest tube clogging. We evaluated the intraluminal clot formation inside chest tubes using high-speed camera imaging and postexplant histology analysis of thrombus. The chest tube clogging was tested (MAS vs. control) in acute hemothorax porcine models (n = 5). The whole tubes with blood clots were fixed with formalin-acetic acid solution and cut into cross-sections, proceeded for H&E-stained paraffin-embedded tissue sections (MAS sections, n = 11; control sections, n = 11), and analyzed. As a separate effort, a high-speed camera (FASTCAM Mini AX200, 100-mm Zeiss lens) was used to visualize the whole blood clogging pattern inside the chest tube cross-sectional view. Histology revealed a thin string-like fibrin deposition, which showed spiral eddy or aggregate within the blood clots in most sections of Group MAS, but not in those of the control group. Histology findings were compatible with high-speed camera views. The high-speed camera images showed a device-specific intraluminal blood "swirling" pattern. Our findings suggest that a continuous spiral flow in blood within the chest tube (MAS vs. static control) contributes to the formation of a spiral string-like fibrin network during consumption of coagulation factors. As a result, the spiral flow may prevent formation of thick band-like fibrin deposits sticking to the inner tube surface and causing tube clogging, and thus may positively affect chest tube patency and drainage.

Attenuation Coefficient Parameter Computations for Tissue Composition Assessment of Carotid Atherosclerotic Plaque in Vivo.

Quantitative ultrasound has been used to assess carotid plaque tissue composition. Here, we compute the attenuation coefficient (AC) in vivo with the optimum power spectral shift estimator (OPSSE) and reference phantom method (RPM), extract AC parameters and form parametric maps. Differences between OPSSE and RPM AC parameters are computed. Relationships between AC parameters, surgical scores and histopathology assessments are examined. Kendall's τ correlations between OPSSE AC and surgical scores are significant, including those between cholesterol and Standard Deviation (adjusted p = 0.038); thrombus and Minimum (adjusted p = 0.002), Maximum (adjusted p = 0.021) and Standard Deviation (adjusted p = 0.001); ulceration and Average (adjusted p = 0.033), Median (unadjusted p = 0.013), Maximum (unadjusted p = 0.039) and Mode (adjusted p = 0.009). The strongest correlations with histopathology are percentage cholesterol and Median OPSSE (unadjusted p = 0.007); percentage hemorrhage and Minimum OPSSE (adjusted p < 0.001); hemosiderin score and Median OPSSE (adjusted p = 0.010); and percentage calcium and Percentage Non-physical RPM Pixels (unadjusted p = 0.014). Kruskal-Wallis H and Dunn's post hoc tests have the ability to distinguish between groups (p < 0.05). Results suggest AC parameters may assist in vivo evaluation of carotid plaque vulnerability.

A novel, rapid, and low cost method for preparing tissues with metallic stents for routine histology.

BACKGROUND: Coronary artery stenting has become a common procedure and cardiovascular pathology specimens containing these metallic stents are accordingly becoming common. Histologic examination of stented vessels is imperative, but special techniques are needed due to the presence of metal within the tissue. We describe a rapid and inexpensive method for preparing stented vascular specimens for routine histology suitable for use in almost any histology laboratory. DESIGN: After formalin fixation and decalcification, stented vascular segments were freeze-embedded and sectioned using a handheld power micro cutoff wheel tool into ~1 mm slices. Sections were allowed to thaw and the strut shards removed with fine forceps. No longer containing metal, the sections were processed for routine paraffin embedding, microtomy and staining. RESULTS: Histologic sections showed only minor tissue disruption around the stent struts. In our experience with 25 stented arteries (mean interval from implantation 5.6 years), the mean subjective section quality score was 4.1 out of 5. The position of each strut could easily be determined, along with neointimal in-stent restenosis and thrombosis. Local reaction to each strut could be surmised even if minor tissue disruption occurred. The entire process was completed in 2-3 days. The incremental cost over that of routine histology is nominal. CONCLUSION: This method for examining stented vascular segments histologically could readily be applied in most pathology laboratories and serves as a highly practical solution to dilemma of examining stents histologically.

[Relevance of complete blood count parameters in the assessment of acute coronary syndromes: a combined hematological and cardiological perspective]. / Alterazioni dell'emocromo nella sindrome coronarica acuta: ematologi e cardiologi a confronto.

The aim of this review is to explore the available evidence concerning the relationship between the different parameters of the complete blood count, its pathophysiological changes and cardiovascular disease, specifically focusing on the acute ischemic setting. Erythrocytes, leukocytes and platelets undergo significant and more or less durable changes over time in response to conditions of systemic inflammatory, infectious and neoplastic disease. This is the reason why blood cell count parameters can (and should) be implemented in the global assessment of the patient with acute coronary syndrome.From the literature review it emerges that anemia and thrombocytopenia have an independent negative prognostic role in the medium and long term, being markers of the overall frailty of patients with ischemic heart disease. On the other hand, essential thrombocythemia and polycythemia vera, two chronic myeloproliferative neoplasms, are characterized by an important increase in thrombotic risk. Both conditions are given a brief description for the particular importance of the close collaboration between cardiologists and hematologists in the diagnosis and treatment of these diseases in the context of ischemic heart disease.

Feasibility of a circulation model for the assessment of endovascular recanalization procedures and periprocedural thromboembolism in-vitro.

Aim of this study was to establish a simple and highly reproducible physiological circulation model to investigate endovascular device performance. The developed circulation model included a pneumatically driven pulsatile pump to generate a flow rate of 2.7 L/min at 70 beats per minute. Sections from the superficial femoral arteries were used in order to simulate device/tissue interaction and a filter was integrated to analyze periinterventional thromboembolism of white, red and mixed thrombi. The working fluid (3 L) was a crystalloid solution constantly tempered at 36.5 °C. To evaluate the model, aspiration thrombectomy, stent-implantation and thrombectomy with the Fogarty catheter were performed. Usability of the model was measured by the System Usability Scale (SUS) - Score. Histological specimens were prepared and analyzed postinterventional to quantify tissue/device interaction. Moreover, micro- and macroembolism were evaluated for each thrombus entity and each device. Results were tested for normality using the D'Agostino-Pearson test. Statistical comparisons of two groups were performed using the Student's t-test. All devices were able to remove the occlusions after a maximum of 2 attempts. First-pass-recanalization was not fully achieved for aspiration thrombectomy of mixed thrombi (90.6%), aspiration thrombectomy of red thrombi (84.4%) and stent-implantation in occlusions of red thrombi (92.2%). Most micro- and macroembolism were observed using the Fogarty catheter and after stent-implantation in occlusions of white thrombi. Histological examinations revealed a significant reduction of the vascular layers suggesting vascular damage after use of the Fogarty catheter (327.3 ± 3.5 µm vs. 440.6 ± 3.9 µm; p = 0.026). Analysis of SUS rendered a mean SUS-Score of 80.4 which corresponds to an excellent user acceptability of the model. In conclusion, we describe a stable, easy to handle and reproducible physiological circulation model for the simulation of endovascular thrombectomy including device performance and thromboembolism.

Capped antithrombin III dosing is cost effective in the management of asparaginase-associated thrombosis.

Asparaginase therapy induces a transient antithrombin III (ATIII) deficiency, which contributes to the risk of asparaginase-induced thrombosis. At Cincinnati Children's Hospital Medical Center, management of asparaginase-induced thrombosis includes ATIII supplementation during therapeutic anticoagulation with enoxaparin. Due to the expense associated with ATIII, a capped dosing approach for ATIII was evaluated in this population. Peak ATIII levels were obtained following capped doses to evaluate response. In this pilot evaluation, 11 patients received a total of 138 capped doses for a total cost savings of $803 782. This pilot evaluation represents the first reported analysis of capped ATIII dosing in oncology patients.

Characteristics and outcomes associated with 30-day readmissions following acute coronary syndrome 2000-2013: the Acute Coronary Syndrome Israeli Survey.

BACKGROUND: Readmissions following acute myocardial infarction are associated with poor outcomes and a heavy economic burden. There are few evidence-based data on the characteristics and outcomes of patients readmitted following acute coronary syndrome. We explored the incidence and outcomes of patients readmitted after an acute coronary syndrome in the past decade. METHODS: The study population comprised all acute coronary syndrome patients who were enrolled and prospectively followed up in the biennial Acute Coronary Syndrome Israeli Survey from 2000 to 2013. Multivariate analysis identified factors independently associated with readmission and long-term mortality. RESULTS: There were 13,010 study patients, of whom 556 (4.2%) had an unplanned readmission within 30 days of the index event. Stent thrombosis during the index hospitalisation (odds ratio (OR) 8.43; 95% confidence interval (CI) 4.11-16.07; P<0.001), female sex (OR 1.34; 95% CI 1.1-1.63; P=0.003), older age (>65 years; OR 1.28; 95% CI 1.06-1.55; P=0.011), and lack of dual-antiplatelet therapy (OR 1.52; 95% CI 1.25-1.86; P<0.001) were independently associated with readmission. Readmitted patients were less likely to have been treated with guideline-directed medical therapy during hospitalisation and at discharge, and were less likely to have undergone coronary angiography. A strong trend towards decline in readmission rates following acute coronary syndrome was observed between 2000 and 2013 (P<0.001). However, the association between readmission and poor long-term outcome was more pronounced among patients readmitted during more recent years (2008-2013). CONCLUSIONS: Patients readmitted to hospital following acute coronary syndrome comprise an undertreated, high-risk cohort. Our findings indicate that despite a significant decline in readmission rates following acute coronary syndrome over the past decade, readmission within 30 days following acute coronary syndrome still portends a grave outcome.

Prospective Assessment of Clinical Risk Factors and Biomarkers of Hypercoagulability for the Identification of Patients with Lung Adenocarcinoma at Risk for Cancer-Associated Thrombosis: The Observational ROADMAP-CAT Study.

BACKGROUND: The aim of this prospective study was to identify the most clinically relevant hypercoagulability biomarkers in lung adenocarcinoma patients for elaboration of an improved risk assessment model (RAM) for venous thromboembolism (VTE). SUBJECTS, MATERIALS, AND METHODS: One hundred fifty ambulatory patients with lung adenocarcinoma were prospectively enrolled. Thrombin generation, procoagulant phospholipid-dependent clotting time (Procoag-PPL), tissue factor activity (TFa), factor VIIa (FVIIa), factor V (FV), antithrombin, D-Dimers, P-selectin, and heparanase levels were assessed in platelet-poor plasma at inclusion (baseline) and at the end of the third chemotherapy cycle (third chemotherapy). Cox regression analysis was used to identify independent VTE predictors. RESULTS: At baseline, patients had significantly attenuated thrombin generation, shorter Procoag-PPL, higher levels of TFa, D-Dimers, and heparanase, and lower levels of FVIIa and P-selectin, compared with controls. A significant increase in Procoag-PPL, FV, and FVIIa and a decrease of P-selectin levels were observed between baseline and third chemotherapy. Hospitalization within the last 3 months prior to assessment, time since cancer diagnosis less than 6 months, mean rate index (MRI) of thrombin generation, and Procoag-PPL were independently associated with symptomatic VTE. Accordingly, a prediction model including Procoag-PPL and MRI showed significant discriminating capacity (area under the curve: 0.84). CONCLUSION: Ambulatory patients with lung adenocarcinoma may display pronounced blood hypercoagulability due to decreased Procoag-PPL, increased endothelial cell activation, and increased degradation of fibrin. Incorporation of Procoag-PPL and MRI of thrombin generation may improve the accuracy of a VTE-RAM in the above setting. IMPLICATIONS FOR PRACTICE: The prospective ROADMAP-CAT study identified two biomarkers of hypercoagulability, the procoagulant phospholipid-dependent clotting time (Procoag-PPL) and the mean rate index (MRI) of the propagation phase of thrombin generation assessed with the Calibrated Automated Thrombinoscope, as being clinically relevant for the classification of ambulatory patients with lung adenocarcinoma receiving a maximum of one cycle of chemotherapy into high and intermediate/low risk for venous thromboembolism. Measurement of Procoag-PPL and MRI within 1 month after the administration of the first chemotherapy cycle provides significant accuracy of the assessment. Association of the Procoag-PPL and MRI with the clinical risk assessment model for cancer-associated thrombosis in ambulatory patients with solid tumors (COMPASS-CAT RAM) further improved its accuracy.

In vitro and in vivo assessment of oxygenator blood volume for the prediction of clot formation in an ECMO circuit (theory and validation).

INTRODUCTION: Clotting is one of the major causes of mortality and morbidity during extracorporeal membrane oxygenation (ECMO). A large meta-analysis study suggests that 29% of patients require the oxygenator to be replaced during ECMO. As clots usually form in the oxygenator, the oxygenator blood volume (OXBV) decreases over time. The currently used pressure gradient as a predicator of clot formation is unreliable. OBJECTIVE: The aim of this study was to develop and validate ultrasound dilution technology in a quantitative assessment of clotting, using measurements of OXBV. METHODS: OXBV was measured using the ELSA monitor (Transonic Systems Inc., Ithaca, NY, USA) from the transit time of a saline bolus passing through the oxygenator as recorded by a sensor placed after the oxygenator. The accuracy and reproducibility (coefficient of variation [CV]) of OXBV measurement and its independence from ECMO flow was assessed in vitro in lambs and from a clinical data archive. RESULTS: The in vitro accuracy compared with volumetric measurements of OXBV of 22-134 ml at flows of 300-700 ml/min was -0.8±6.6%. For an OXBV of 355 ml at flows of 1020-7000 ml/min, accuracy was -0.4±1.6%. In 88 animal OXBV measurements, the CV was 1.49±1.12%. For an OXBV of 153 (range 42-387 ml), clinical measurements at flow ranged from 210-5960 ml/min, with a CV of 3.20±2.44 %. CONCLUSION: Dilution technology has the ability to accurately and reproducibly assess the clotting process in the oxygenator. Larger studies are needed to establish guidelines for the prediction of imminent clotting and may help to avoid unnecessary circuit changes.

Primary Human Lung Alveolus-on-a-chip Model of Intravascular Thrombosis for Assessment of Therapeutics.

Pulmonary thrombosis is a significant cause of patient mortality; however, there are no effective in vitro models of thrombi formation in human lung microvessels that could also assess therapeutics and toxicology of antithrombotic drugs. Here, we show that a microfluidic lung alveolus-on-a-chip lined by human primary alveolar epithelium interfaced with endothelium and cultured under flowing whole blood can be used to perform quantitative analysis of organ-level contributions to inflammation-induced thrombosis. This microfluidic chip recapitulates in vivo responses, including platelet-endothelial dynamics and revealed that lipopolysaccharide (LPS) endotoxin indirectly stimulates intravascular thrombosis by activating the alveolar epithelium, rather than acting directly on endothelium. This model is also used to analyze inhibition of endothelial activation and thrombosis due to a protease activated receptor-1 (PAR-1) antagonist, demonstrating its ability to dissect complex responses and identify antithrombotic therapeutics. Thus, this methodology offers a new approach to study human pathophysiology of pulmonary thrombosis and advance drug development.

Global deregulation of ginseng products may be a safety hazard to warfarin takers: solid evidence of ginseng-warfarin interaction.

Recent global deregulation of ginseng as the table food raises our concern about the possible ginseng-warfarin interaction that could be life-threatening to patients who take warfarin for preventing fatal strokes and thromboembolism while using ginseng products for bioenergy recovery. Here we show that quality-control ginsenosides, extracted from ginseng and containing its major active ingredients, produce dose- and time-dependent antagonism in rats against warfarin's anti-coagulation assessed by INR and rat thrombosis model. The interactions between ginsenosides and warfarin on thrombosis, pharmacokinetics, activities of coagulation factors and liver cytochrome P450 isomers are determined by using thrombosis analyzer, UPLC/MS/MS, ELISA and real-time PCR, respectively. The antagonism correlates well with the related pharmacokinetic interaction showing that the blood plateaus of warfarin reached by one-week warfarin administration are significantly reduced after three-week co-administration of warfarin with ginsenosides while 7-hydroxywarfarin is increased. The one-week warfarin and three-week warfarin-ginsenosides regimen result in restoring the suppressed levels by warfarin of the coagulating factors II, VII and protein Z, and significantly enhance activities of P450 3A4 and 2C9 that metabolize warfarin. The present study, for the first time, provides the solid evidence to demonstrate the warfarin-ginsenoside interaction, and warns the warfarin users and regulation authorities of the dangerous interaction.

In-vitro assessment of the effect of dabigatran on thrombosis of adult and neonatal plasma: comparisons using thromboelastography and microscopic visualization of fibrin clot structure.

: Thromboelastography (TEG) is a global assay used for evaluating features of clot formation in vitro. Dabigatran is a reversible direct inhibitor of thrombin that has not been studied in neonates using a sophisticated global assay, such as TEG. Neonatal hemostasis differs from adult hemostasis in both quantitative and qualitative characteristics. Our aim was to compare the TEG clotting profile of neonatal and adult platelet-poor plasma when exposed to different concentrations of dabigatran. We used commercially collected adult pooled plasma and neonatal cord blood collected from placentas of healthy full term newborns. Platelet-poor plasma was isolated, pooled, and frozen. Prior to experiment, plasma was thawed and filtered. A reaction mixture of CaCl2, corn trypsin inhibitor, tissue factor, and dabigatran in imidazole buffer was mixed with plasma in a TEG cup. Time to clot initiation (R-time), speed of clot strengthening (α-angle), and maximum clot strength (maximal amplitude) were measured. Scanning electron microscopy was performed to evaluate fibrin clot structure. Without dabigatran, there was no significant difference in TEG measurements between neonatal and adult samples. However, neonatal plasma clotting with dabigatran had slower onset, slower speed, and weaker clots that were more porous with thicker fibers, compared with adult plasma clotting. Thus, neonatal plasma may be more sensitive to dabigatran as assessed by our in-vitro TEG study.

Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura.

Essentials Endothelial injury is thought to be a key event in thrombotic thrombocytopenic purpura (TTP). Endothelial and cardiac damages were assessed in a model of TTP using ADAMTS-13 knockout mice. Damages of cardiac perfusion and function were associated with nitric oxide pathway alteration. Endothelial dysfunction constitutes a critical event in TTP development and cardiac injury. SUMMARY: Background Cardiac alterations represent a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). Endothelial injury remains poorly defined, but seems to be a key initiating event leading to the formation of platelet-rich thrombi in TTP patients. Objectives To assess the changes in endothelial function and the induced cardiac damage in a mouse model of TTP. Patients/methods We used an animal model in which TTP-like symptoms are triggered by injection of 2000 units kg-1 of recombinant von Willebrand factor in ADAMTS-13 knockout mice. Results These mice developed TTP-like symptoms, i.e. severe thrombocytopenia, schistocytosis, and anemia. On day 2, magnetic resonance imaging demonstrated a decrease in left ventricular perfusion associated with alteration of left ventricular ejection fraction, fractional shortening, and cardiac output, suggesting early systolic dysfunction. This was associated with decrease in endothelium-mediated relaxation responses to acetylcholine in mesenteric and coronary arteries, demonstrating severe early endothelial dysfunction. In parallel, we showed decreased cardiac expression of endothelial nitric oxide (NO) synthase and increased expression of antioxidant enzymes, suggesting alteration of the NO pathway. At this time, cardiac immunohistochemistry revealed an increase in the expression of VCAM-1 and E-selectin. Conclusion This study provides evidence that the heart is a sensitive target organ in TTP, and shows, for the first time, strong mesenteric and coronary endothelial dysfunction in an induced-TTP model. The mechanisms incriminated are the occurrence of a pro-oxidant state, and proadhesive and proinflammatory phenotypes. This previously largely unrecognized vascular dysfunction may represent an important contributor to the systemic organ failure occurring in TTP.

First pass perfusion imaging to improve the assessment of left ventricular thrombus following a myocardial infarction.

PURPOSE: To assess whether a first-pass perfusion sequence (FPP) improved the detection of left ventricular thrombus (LVT). MATERIALS AND METHODS: Three hundred and twenty-nine patients with a first STEMI were prospectively included to undergo cardiac magnetic resonance (CMR) at baseline and after a 3-month follow-up. A CMR delayed analysis was performed by three blinded examiners (2 CMR experts and 1 novice) according to a two-step reading protocol. First, an analysis was performed on cine CMR and late gadolinium enhancement (routine stage). Then, the FPP stage was performed following initial protocol along with a FPP sequence. RESULTS: LVT was found in 31 out of a total of 638 (4.9%) CMR scans, affecting 30 (9.1%) individuals. All were located in the left ventricular apex. The FPP stage improved significantly the LVT diagnosis for all readers, in 10 and 13 cases (32% and 42%) of LVT suspicion for the experts and 16 cases (41%) for the novice. Respectively 1, 2 and 6 LVT were not detected during the routine stage by the CMR experts and the novice. For the novice, the FPP stage improved diagnosis sensitivity from 78.1 to 91.2%. CONCLUSIONS: The prevalence of LVT following a myocardial infarction reached 9.1% and increased with the reading of FPP sequence. The FPP stage improved expert diagnostic certitude and the novice's abilities to reach expert level.

The utility of International Society on Thrombosis and Haemostasis-Bleeding Assessment Tool and other bleeding questionnaires in assessing the bleeding phenotype in two platelet function defects.

The main objective of this study is to investigate the utility of International Society on Thrombosis and Haemostasis-Bleeding Assessment Tool (ISTH-BAT) in comparison with the condensed form of Molecular and Clinical Markers for the Diagnosis and Management of type 1 and WHO BATs, in assessing bleeding in two well known and clinically significant platelet function defects. Thirty-eight patients previously diagnosed with Glanzmann's thrombasthenia and 10 with Bernard-Soulier syndrome (BSS) were analyzed. Bleeding scores were significantly higher than that of controls using both electronic bleeding questionnaire (eBQ) and ISTH-BAT with no significant difference between both tools. ISTH-BAT had a sensitivity, specificity, positive predictive value and negative predictive value of 100%, 76.2%, 0.9 and 1. This was closely similar to eBQ. Both ISTH-BAT and eBQ are efficient in BSS and Glanzmann's thrombasthenia. However, given the ISTH recommendation, ISTH-BAT should be adopted. Larger study including other platelet defects will enhance its utility and support the integration of bleeding scores with standardized laboratory testing to allow for a universal diagnostic approach to patients with suspected bleeding disorders.

Dynamic and quantitative assessment of blood coagulation using optical coherence elastography.

Reliable clot diagnostic systems are needed for directing treatment in a broad spectrum of cardiovascular diseases and coagulopathy. Here, we report on non-contact measurement of elastic modulus for dynamic and quantitative assessment of whole blood coagulation using acoustic radiation force orthogonal excitation optical coherence elastography (ARFOE-OCE). In this system, acoustic radiation force (ARF) is produced by a remote ultrasonic transducer, and a shear wave induced by ARF excitation is detected by the optical coherence tomography (OCT) system. During porcine whole blood coagulation, changes in the elastic property of the clots increase the shear modulus of the sample, altering the propagating velocity of the shear wave. Consequently, dynamic blood coagulation status can be measured quantitatively by relating the velocity of the shear wave with clinically relevant coagulation metrics, including reaction time, clot formation kinetics and maximum shear modulus. The results show that the ARFOE-OCE is sensitive to the clot formation kinetics and can differentiate the elastic properties of the recalcified porcine whole blood, blood added with kaolin as an activator, and blood spiked with fibrinogen.