48 research outputs found
Prophylaxis in von Willebrand Disease: Coming of Age?
Although in most cases von Willebrand disease (VWD) is a mild disorder, a subgroup of patients experience frequent bleeding. In contrast to severe hemophilia in which prophylaxis is the accepted standard of care, this is less frequently used in VWD. Most type 1 VWD patients can be adequately managed with episodic desmopressin and tranexamic acid. In patients with more severe disease, especially those with type 3 VWD, joint bleeds, epistaxis, menorrhagia, and gastrointestinal bleeding are problematic and usually require treatment with von Willebrand factor/factor VIII (VWF/FVIII) concentrate. While in the past these patients were managed with on-demand VWF/FVIII concentrate, several recent reports have demonstrated the value of prophylactic treatment. Despite some uncertainties about the economic impact of treatment of severe VWD, prophylaxis with VWF concentrate should now be considered as the standard of care for the more severe end of the spectrum of affected individuals. The recent introduction of recombinant VWF concentrate is likely to improve the acceptability of prophylaxis in VWD
Residual vein thrombosis and D-dimer for optimizing duration of anticoagulation in idiopathic deep vein thrombosis.
Experimental assessment on exploiting low carbon ethanol fuel in a light-duty dual-fuel compression ignition engine
Compression ignition (CI) engines are widely used in modern society, but they are also recognized as a significative source of harmful and human hazard emissions such as particulate matter (PM) and nitrogen oxides (NOx). Moreover, the combustion of fossil fuels is related to the growing amount of greenhouse gas (GHG) emissions, such as carbon dioxide (CO2). Stringent emission regulatory programs, the transition to cleaner and more advanced powertrains and the use of lower carbon fuels are driving forces for the improvement of diesel engines in terms of overall efficiency and engine-out emissions. Ethanol, a light alcohol and lower carbon fuel, is a promising alternative fuel applicable in the dual-fuel (DF) combustion mode to mitigate CO2 and also engine-out PM emissions. In this context, this work aims to assess the maximum fuel substitution ratio (FSR) and the impact on CO2 and PM emissions of different nozzle holes number injectors, 7 and 9, in the DF operating mode. The analysis was conducted within engine working constraints and considered the influence on maximum FSR of calibration parameters, such as combustion phasing, rail pressure, injection pattern and exhaust gas recirculation (EGR). The experimental tests were carried out on a single-cylinder light-duty CI engine with ethanol introduced via port fuel injection (PFI) and direct injection of diesel in two operating points, 1500 and 2000 rpm and at 5 and 8 bar of brake mean effective pressure (BMEP), respectively. Noise and the coefficient of variation in indicated mean effective pressure (COVIMEP) limits have been chosen as practical constraints. In particular, the experimental analysis assesses for each parameter or their combination the highest ethanol fraction that can be injected. To discriminate the effect on ethanol fraction and the combustion process of each parameter, a one-at-a-time-factor approach was used. The results show that, in both operating points, the EGR reduces the maximum ethanol fraction injectable; nevertheless, the ethanol addition leads to outstanding improvement in terms of engine-out PM. The adoption of a 9 hole diesel injector, for lower load, allows reaching a higher fraction of ethanol in all test conditions with an improvement in combustion noise, on average 3 dBA, while near-zero PM emissions and a reduction can be noticed, on the average of 1 g/kWh, and CO2 compared with the fewer nozzle holes case. Increasing the load insensitivity to different holes number was observed
Drug-Related Cardiotoxicity for the Treatment of Haematological Malignancies in Elderly.
Meyer Paul Hugo. Diderot oder die Ambivalenz der Aufklärung, Neumann, 1987. In: Recherches sur Diderot et sur l'Encyclopédie, n°4, 1988. pp. 164-165
The current state of adverse event reporting in hemophilia
Introduction: Replacement of the missing clotting factor is the mainstay of haemophilia treatment. Whilst historically many haemophilia patients were infected with blood-borne vi-ruses transmitted via plasma-derived products, nowadays the formation of alloantibodies against the missing clotting factor is the main adverse event of treatment.
Areas covered: This paper provides an overview of the current national and international adverse event reporting systems, what these surveillance schemes taught us about side effects of the products presently in use, and elaborates on how to adapt these systems to the challeng-es we face with the changing treatment landscape.
Expert commentary: Treatment of inherited bleeding disorders was accompanied by severe complications in the past, resulting in major morbidity and mortality. Current products are much safer, but still require monitoring via efficient safety surveillance systems. Adverse events are reported in national and international systems. With many new products entering the market, as well as non-factor replacement therapies, new safety issues may arise. It is im-portant to identify potential adverse events early by making surveillance systems suitable to pick up unknown or unexpected effects, and to recognize and communicate patterns of ad-verse events rapidly
Caution in using the activated partial thromboplastin time to monitor argatroban in COVID-19 and vaccine-induced immune thrombocytopenia and thrombosis (VITT)
Introduction
Argatroban is licensed for patients with heparin-induced thrombocytopenia and is conventionally monitored by activated partial thromboplastin time (APTT) ratio. The target range is 1.5 to 3.0 times the patients’ baseline APTT and not exceeding 100 s, however this baseline is not always known. APTT is known to plateau at higher levels of argatroban, and is influenced by coagulopathies, lupus anticoagulant and raised FVIII levels. It has been used as a treatment for COVID-19 and Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT). Some recent publications have favored the use of anti-IIa methods to determine the plasma drug concentration of argatroban.
Methods
Plasma of 60 samples from 3 COVID-19 patients and 54 samples from 5 VITT patients were tested by APTT ratio and anti-IIa method (dilute thrombin time dTT). Actin FS APTT ratios were derived from the baseline APTT of the patient and the mean normal APTT.
Results
Mean APTT ratio derived from baseline was 1.71 (COVID-19), 1.33 (VITT) compared to APTT ratio by mean normal 1.65 (COVID-19), 1.48 (VITT). dTT mean concentration was 0.64 µg/ml (COVID-19) 0.53 µg/ml (VITT) with poor correlations to COVID-19 baseline APTT ratio r2 = 0.1526 p <0.0001, mean normal r2 = 0.2188 p < 0.0001; VITT baseline APTT ratio r2 = 0.04 p < 0.001, VITT mean normal r2 = 0.0064 p < 0.001.
Conclusions
We believe that dTT is a superior method to monitor the concentration of argatroban, we have demonstrated significant differences between APTT ratios and dTT levels, which could have clinical impact. This is especially so in COVID-19 and VITT
Residual vein thrombosis for assessing duration of anticoagulation after unprovoked deep vein thrombosis of the lower limbs: the extended DACUS study.
Abstract
The safest duration of anticoagulation after idiopathic deep vein thrombosis (DVT) is unknown. We conducted a prospective study to assess the optimal duration of vitamin K antagonist (VKA) therapy considering the risk of recurrence of thrombosis according to residual vein thrombosis (RVT). Patients with a first unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA administration; those without RVT suspended VKA, while those with RVT continued oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment (RVT group) and 1 year after VKA withdrawal (both groups). Among 409 patients evaluated for unprovoked DVT, 33.2% (136 of 409 patients) did not have RVT and VKA was stopped. The remaining 273 (66.8%) patients with RVT received anticoagulants for an additional 21 months; during this period of treatment, recurrent venous thromboembolism and major bleeding occurred in 4.7% and 1.1% of patients, respectively. After VKA suspension, the rates of recurrent thrombotic events were 1.4% and 10.4% in the no-RVT and RVT groups, respectively (relative risk = 7.4; 95% confidence interval = 4.9-9.9). These results indicate that in patients without RVT, a short period of treatment with a VKA is sufficient; in those with persistent RVT, treatment extended to 2 years substantially reduces, but does not eliminate, the risk of recurrent thrombosis