Summary
Blood‐contacting medical devices, such as vascular grafts, stents, heart valves, and catheters, are often used to treat cardiovascular diseases. Thrombus formation is a common cause of ...failure of these devices. This study (i) examines the interface between devices and blood, (ii) reviews the pathogenesis of clotting on blood‐contacting medical devices, (iii) describes contemporary methods to prevent thrombosis on blood‐contacting medical devices, (iv) explains why some anticoagulants are better than others for prevention of thrombosis on medical devices, and (v) identifies future directions in biomaterial research for prevention of thrombosis on blood‐contacting medical devices.
Abstract Triglycerides represent 1 component of a heterogeneous pool of triglyceride-rich lipoproteins (TGRLs). The reliance on triglycerides or TGRLs as cardiovascular disease (CVD) risk biomarkers ...prompted investigations into therapies that lower plasma triglycerides as a means to reduce CVD events. Genetic studies identified TGRL components and pathways involved in their synthesis and metabolism. We advocate that only a subset of genetic mechanisms regulating TGRLs contribute to the risk of CVD events. This “omic” approach recently resulted in new targets for reducing CVD events.
The present study examined the thesis that positive affect may serve to broaden the scope of attentional filters, reducing their selectivity. The effect of positive mood states was measured in two ...different cognitive domains: semantic search (remote associates task) and visual selective attention (Eriksen flanker task). In the conceptual domain, positive affect enhanced access to remote associates, suggesting an increase in the scope of semantic access. In the visuospatial domain, positive affect impaired visual selective attention by increasing processing of spatially adjacent flanking distractors, suggesting an increase in the scope of visuospatial attention. During positive states, individual differences in enhanced semantic access were correlated with the degree of impaired visual selective attention. These findings demonstrate that positive states, by loosening the reins on inhibitory control, result in a fundamental change in the breadth of attentional allocation to both external visual and internal conceptual space.
Objective To determine how length of anticoagulation and clinical presentation of venous thromboembolism influence the risk of recurrence after anticoagulant treatment is stopped and to identify the ...shortest length of anticoagulation that reduces the risk of recurrence to its lowest level.Design Pooled analysis of individual participants’ data from seven randomised trials.Setting Outpatient anticoagulant clinics in academic centres.Population 2925 men or women with a first venous thromboembolism who did not have cancer and received different durations of anticoagulant treatment.Main outcome measure First recurrent venous thromboembolism after stopping anticoagulant treatment during up to 24 months of follow-up.Results Recurrence was lower after isolated distal deep vein thrombosis than after proximal deep vein thrombosis (hazard ratio 0.49, 95% confidence interval 0.34 to 0.71), similar after pulmonary embolism and proximal deep vein thrombosis (1.19, 0.87 to 1.63), and lower after thrombosis provoked by a temporary risk factor than after unprovoked thrombosis (0.55, 0.41 to 0.74). Recurrence was higher if anticoagulation was stopped at 1.0 or 1.5 months compared with at 3 months or later (hazard ratio 1.52, 1.14 to 2.02) and similar if treatment was stopped at 3 months compared with at 6 months or later (1.19, 0.86 to 1.65). High rates of recurrence associated with shorter durations of anticoagulation were confined to the first 6 months after stopping treatment.Conclusion Three months of treatment achieves a similar risk of recurrent venous thromboembolism after stopping anticoagulation to a longer course of treatment. Unprovoked proximal deep vein thrombosis and pulmonary embolism have a high risk of recurrence whenever treatment is stopped.
Summary
Background
Clinical situations occur where expedient assessment of the anticoagulant activity of the direct factor Xa (FXa) inhibitors is required. Although quantitative anti‐FXa (FXa) assays ...can be used to measure plasma levels of apixaban or rivaroxaban, turnaround is often slow and many laboratories do not perform these assays.
Objective
We compared the in vitro effects of apixaban and rivaroxaban on two readily available laboratory tests, the prothrombin time (PT) and activated partial thromboplastin time (APTT), performed with different reagents. We aimed to identify the most sensitive reagents.
Methods
Rivaroxaban or apixaban was added to human plasma at a range of concentrations covering expected peak and trough levels, and concentrations were confirmed using calibrated anti‐FXa assays. Samples were assayed with six PT and seven APTT reagents using different coagulometers.
Results and Conclusions
TriniCLOT PT Excel S was the only reagent to demonstrate sensitivity to apixaban. All of the PT reagents were sensitive to rivaroxaban with TriniCLOT PT Excel S and HemosIL HS PLUS being the most sensitive. Sensitivity to rivaroxaban varied among APTT reagents; four reagents exhibited the greatest responsiveness, and of these, Actin FSL was the most responsive. Commonly used coagulation tests may be useful for assessing the anticoagulant effect of rivaroxaban but not of apixaban. The reason for the different effects of apixaban and rivaroxaban on the PT and APTT is unknown.
Background: Guidelines recommend stopping aspirin and clopidogrel 7 to 10 days before surgery to allow time for replacement of permanently inhibited platelets by newly released uninhibited ...platelets.Objectives: The purpose of the present study was to determine the rate of offset of the anti‐platelet effects of aspirin and clopidogrel after stopping treatment and the proportion of untreated donor platelets that are required to reverse their anti‐platelet effects.Methods: Cohort 1 consisted of 15 healthy subjects who received aspirin 81 mg day−1 or clopidogrel 75 mg day−1 for 7 days and underwent serial blood sampling until platelet function testing results normalized. Cohort 2 consisted of 36 healthy subjects who received aspirin 325 mg day−1, clopidogrel 75 mg day−1, aspirin 81 mg day−1 plus clopidogrel 75 mg day−1 or no treatment for 7 days and underwent a single blood sampling.Results: In cohort 1, arachidonic acid (AA)‐induced light transmission aggregation (LTA) returned to baseline levels in all subjects within 4 days of stopping aspirin, coinciding with the partial recovery of plasma thromboxane B2 concentrations. ADP‐induced LTA did not return to baseline levels until 10 days after stopping clopidogrel. In cohort 2, AA‐induced LTA in patient treated with aspirin reached control levels after mixing with 30% untreated donor platelets whereas ADP‐induced LTA in patients treated with clopidogrel reached control levels only after the addition of 90% or more donor platelets.Conclusions: Platelet aggregation recovers within 4 days of stopping aspirin but clopidogrel must be stopped for 10 days to achieve a normal aggregatory response.
Diatoms are unicellular phytoplankton accounting for ∼40% of global marine primary productivity
1, yet the molecular mechanisms underlying their ecological success are largely unexplored. We use a ...functional-genomics approach in the marine diatom
Phaeodactylum tricornutum to characterize a novel protein belonging to the widely conserved YqeH subfamily
2 of GTP-binding proteins thought to play a role in ribosome biogenesis
3, sporulation
4, and nitric oxide (NO) generation
5. Transgenic diatoms overexpressing this gene, designated
PtNOA, displayed higher NO production, reduced growth, impaired photosynthetic efficiency, and a reduced ability to adhere to surfaces. A fused YFP-PtNOA protein was plastid localized, distinguishing it from a mitochondria-localized plant ortholog.
PtNOA was upregulated in response to the diatom-derived unsaturated aldehyde 2E,4E/Z-decadienal (DD), a molecule previously shown to regulate intercellular signaling, stress surveillance
6, and defense against grazers
7. Overexpressing cell lines were hypersensitive to sublethal levels of this aldehyde, manifested by altered expression of superoxide dismutase and metacaspases, key components of stress and death pathways
8, 9. NOA-like sequences were found in diverse oceanic regions, suggesting that a novel NO-based system operates in diatoms and may be widespread in phytoplankton, providing a biological context for NO in the upper ocean
10.
Summary
Background
In clinical practice, physicians are given the choice of selecting one of two dabigatran doses based on patient characteristics, with the lower dose typically used in patients at a ...higher risk of bleeding.
Objectives
The objectives of the study were to (i) estimate the inter‐ and intra‐patient variability in dabigatran levels with 110 mg (DE110) and 150 mg (DE150) doses, (ii) examine the effect of physicians’ dose selection on levels in DE110 and DE150 subgroups, and (iii) explore whether a single trough measurement identifies patients with extreme levels on subsequent visits.
Methods
In this prospective observational study of 100 patients with atrial fibrillation (AF), peak and trough levels of dabigatran were measured with the Hemoclot® assay at baseline and every 2 months thereafter (maximum four visits).
Results
Inter‐patient variability in dabigatran levels (geometric coefficient of variation gCV, 51–64%) was greater than intra‐patient variability (gCV, 32–40%). Similar medians and distributions of levels were observed in DE110 and DE150 subgroups. Patients receiving DE110 were older, had lower renal function and weighed less than those receiving DE150. Up to 40% of patients whose trough levels were in the upper extremes, and up to 80% of patients whose trough levels were in the lower extremes at baseline, showed subsequent levels that fell in the middle quartiles.
Conclusions
Our data support the practice of selecting the dabigatran dose based upon clinical characteristics because it results in similar levels of drug exposure in patients given DE110 or DE150. They do not support the concept that a single Hemoclot® measurement reliably identifies patients with consistently high or low values.
Many patients with the antiphospholipid antibody syndrome and recurrent thrombosis receive doses of warfarin adjusted to achieve an international normalized ratio (INR) of more than 3.0. However, ...there are no prospective data to support this approach to thromboprophylaxis.
We performed a randomized, double-blind trial in which patients with antiphospholipid antibodies and previous thrombosis were assigned to receive enough warfarin to achieve an INR of 2.0 to 3.0 (moderate intensity) or 3.1 to 4.0 (high intensity). Our objective was to show that high-intensity warfarin was more effective in preventing thrombosis than moderate-intensity warfarin.
A total of 114 patients were enrolled in the study and followed for a mean of 2.7 years. Recurrent thrombosis occurred in 6 of 56 patients (10.7 percent) assigned to receive high-intensity warfarin and in 2 of 58 patients (3.4 percent) assigned to receive moderate-intensity warfarin (hazard ratio for the high-intensity group, 3.1; 95 percent confidence interval, 0.6 to 15.0). Major bleeding occurred in three patients assigned to receive high-intensity warfarin and four patients assigned to receive moderate-intensity warfarin (hazard ratio, 1.0; 95 percent confidence interval, 0.2 to 4.8).
High-intensity warfarin was not superior to moderate-intensity warfarin for thromboprophylaxis in patients with antiphospholipid antibodies and previous thrombosis. The low rate of recurrent thrombosis among patients in whom the target INR was 2.0 to 3.0 suggests that moderate-intensity warfarin is appropriate for patients with the antiphospholipid antibody syndrome.
PDF
