2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants

International audienceIn 2018, the International Council for Standardization in Haematology (ICSH) published a consensus document providing guidance for laboratories on measuring direct oral anticoagulants (DOACs). Since that publication, several significant changes related to DOACs have occurred, including the approval of a new DOAC by the Food and Drug Administration, betrixaban, and a specific DOAC reversal agent intended for use when the reversal of anticoagulation with apixaban or rivaroxaban is needed due to life-threatening or uncontrolled bleeding, andexanet alfa. In addition, this ICSH Working Party recognized areas where additional information was warranted, including patient population considerations and updates in point-of-care testing. The information in this manuscript supplements our previous ICSH DOAC laboratory guidance document. The recommendations provided are based on (1) information from peer-reviewed publications about laboratory measurement of DOACs, (2) contributing author's personal experience/expert opinion and (3) good laboratory practice

A cell spot microarray method for production of high density siRNA transfection microarrays

Peer reviewe

Dynamics of von Willebrand factor reactivity in sickle cell disease during vaso-occlusive crisis and steady state

Essentials The role of von Willebrand Factor (VWF) in the pathophysiology of sickle cell disease is unclear. We assessed markers of VWF during admission for vaso-occlusive crisis (VOC) and steady state. VWF reactivity was higher during VOC and was associated with inflammation and neutrophil activation. Hyper-adhesive VWF may promote VOC in sickle cell disease. Summary: Background Endothelial activation plays a central role in the pathophysiology of vaso-occlusion in sickle cell disease (SCD), facilitating adhesive interactions with circulating blood cells. Upon activation, various adhesive molecules are expressed, including von Willebrand factor (VWF). Increased VWF levels have been observed in patients with SCD during steady state. However, the role of VWF in the pathogenesis of SCD vaso-occlusion is unclear. Objectives To longitudinally assess the quantity and reactivity of VWF and its regulating protease ADAMTS-13 during vaso-occlusive crisis (VOC). Methods In this observational study, we obtained sequential blood samples in adult SCD patients during VOC. Results VWF reactivity was significantly higher during VOC (active VWF, VWF glycoprotein Ib-binding activity, and high molecular weight multimers), whereas platelet count and levels of ADAMTS-13 antigen and ADAMTS-13 activity were concomitantly lower than during steady state. Levels of VWF antigen, VWF propeptide (VWF:pp) and ADAMTS-13 specific activity did not change during VOC. VWF reactivity correlated strongly with markers of inflammation and neutrophil activation, and was inversely correlated with the platelet count. In patients who developed acute chest syndrome, levels of VWF, VWF:pp and active, hyperadhesive VWF were significantly higher, whereas ADAMTS-13 activity was lower, than in patients without this complication. Conclusions We provide the first evidence that VOC in SCD is associated with increased reactivity of VWF, without a pronounced ADAMTS-13 deficiency. This hyper-reactivity may be explained by resistance of VWF to proteolysis, secondary to processes such as inflammation and oxidative stress. Hyperadhesive VWF, scavenging blood cells in the microcirculation, may thereby amplify and sustain VOC in SCD

Beyond economics : understanding the decision-making of German small private landlords in terms of energy efficiency investment

The German government aims to achieve virtually climate-neutral building stock by 2050 to tackle climate change. To realise this goal, comprehensive policy packages based on neoclassical economic theory are in place to foster energy efficiency investment. However, in the building sector, there is increasingly a gap between this aspiration and the reality. It is claimed that one of the main reasons for this is that the existing policy framework fails to address the specific characteristics and needs of different groups of building owners. This is a particular challenge in Germany, where 80% of all dwellings are owned privately and 37% are rented out by small private landlords (SPL). Despite the significant numbers of SPL, they often follow black box decision-making processes when considering energy renovations. In this study, the author uses an explanatory model to understand the decision-making processes of SPL, combining theoretical aspects from different research disciplines. This model was applied to a low-demand housing market in a neighbourhood in the Ruhr area. Eighteen semi-structured interviews (each lasting between 37 and 115 min) were conducted, demonstrating that in addition to economic factors, the values, beliefs, norms and routines of SPL - as well as their personal capabilities and contextual factors - play an important role in their decision-making. Based on the findings, recommendations are made for enhancing the effectiveness of existing energy efficiency policies and other supporting instruments (e.g. tenancy law and social legislation), tailored to the specific needs of SPL

Brown bear research in Europe: a review of the data collected and their value for conservation

Europe is a mosaic of landscapes shaped by human presence and activity, nevertheless it still harbors ~18 000 brown bears, clustered in 10 populations. Brown bear management and conservation in Europe is carried out by national/regional governmental agencies and through the involvement of universities and research institutions, NGOs, protected areas’ administrations, and hunting associations. Due to their cultural and charismatic value, brown bears have been largely studied under various aspects of their biology, ecology, and management and much of this knowledge has been gathered through the collaboration of these various agents. Nevertheless, the data collected have been only partially used for research and published in the peer-reviewed literature and, therefore, may not be fully available to the scientific community and conservation practitioners. In addition, data collection and research efforts are often fragmented at an administrative level, and can be sparse and scattered or even lacking in some parts of the species range due to limited funding. Here we summarize the ecological data collected for the 10 brown bear populations in Europe, focusing primarily on movement, genetic, demographic, and diet data. We report the type of data collected, the methods as well as the geographic and temporal coverage of the data collection, the overall sample sizes, if the data were obtained at the population or country/regional level, what the data have been used for, and if results have been published. We use this information first to reveal the substantial amount of valuable data collected for the brown bear throughout Europe. Second, we identify existing gaps in knowledge and data collection and prioritize future efforts needed as well as areas where research funding may be more urgent. Third, we highlight the potentials for integrating the overall knowledge so far collected for improving understanding of brown bear ecology in the human-dominated European landscape and implementing more effective management and conservation planning