Monitoring of anticoagulation in thrombotic antiphospholipid syndrome

Anticoagulation is central to the management of thrombotic antiphospholipid syndrome (APS). The standard anticoagulant treatment for thrombotic APS is life-long warfarin or an alternative vitamin K antagonist. The role of direct oral anticoagulants for thrombotic APS is not established due to the lack of definitive evidence and has recently been addressed in international guidance. Other anticoagulant options include low-molecular-weight heparin, unfractionated heparin and fondaparinux. In APS patients, lupus anticoagulant can affect phospholipid-dependent coagulation monitoring tests, so that they may not reflect true anticoagulation intensity. Accurate assessment of anticoagulation intensity is essential, to optimise anticoagulant dosing and facilitate thrombus resolution; minimise the risk of recurrent thrombosis or bleeding; inform assessment of whether recurrent thrombosis is related to breakthrough thrombosis while on therapeutic anticoagulation, subtherapeutic anticoagulation, non-adherence or spurious results; and guide the management of bleeding. Knowledge of anticoagulant intensity also informs assessment and comparison of anticoagulation regimens in clinical studies. Considerations regarding anticoagulation dosing and/or monitoring of thrombotic APS patients underpin appropriate management in special situations, notably APS-related severe renal impairment, that may occur in APS or APS/systemic lupus erythematosus-related nephropathy or catastrophic APS; and APS-related thrombocytopenia. Anticoagulant dosing and monitoring in thrombotic APS patients also requires consideration in anticoagulant-refractory APS and pregnancy. In this review, we summarise the tests generally used in monitoring anticoagulant therapy, use of the main anticoagulants considered for thrombotic APS, lupus anticoagulant effects on anticoagulation monitoring tests, and strategies for appropriate anticoagulant monitoring in thrombotic APS

Direct Oral Anticoagulants for Thromboprophylaxis in Patients with Antiphospholipid Syndrome

The current mainstay of the treatment and secondary thromboprophylaxis of thrombotic antiphospholipid syndrome (APS) is anticoagulation with warfarin or other vitamin K antagonists (VKAs). In addition to their well-known limitations, VKAs are often problematic in APS patients because of the variable sensitivity of thromboplastins to lupus anticoagulant. As a result, the international normalized ratio may not accurately reflect the intensity of anticoagulation. Direct oral anticoagulants (DOACs) are established as therapeutic alternatives to VKAs for a wide range of indications, including the treatment and secondary prevention of venous thromboembolism. Definition of the role of DOACs in the treatment of thrombotic APS is emerging with the results of recent and ongoing clinical studies. This review focuses on the current situation with regard to DOACs for secondary thromboprophylaxis in APS and issues pertinent to DOAC use in APS patients, as well as potential future directions

Under crossfire: thromboembolic risk in systemic lupus erythematosus

Cerebral and cardiovascular ischaemic events are frequent complications of SLE and constitute primary causes of permanent damage. However, the pathogenic determinants of an increased thromboembolic risk in patients with SLE are only partially understood. Atherosclerosis constitutes fertile soil for the development of thrombosis and shows disproportionately high prevalence and progression rates in patients with SLE. aPLs are independent risk factors for acute thrombosis but can also prompt long-term vascular inflammation. Aberrant interactions among immune cells and dysfunctions in the deployment of the coagulation cascade have historically been less explored in SLE, but recent evidence suggests they can also play a critical role at the crossroads between inflammation and haemostasis. In this review we discuss how different prothrombotic mechanisms can be prompted by and synergize with SLE-specific pathogenic events and speculate about novel potential directions for research and drug development

Faith, Secularism, and the Need for Interfaith Dialogue in Writing Center Work

This article argues that religious and secularist identities complement and intersect in political ways with race, class, gender, sexuality, and nationality and that they inform writing center practice because belief exists along a spectrum that involves all writing center inhabitants and affects all writing-centered conversations. We suggest that this spectrum of faith is evocative of the spectrums that theorists of race, gender, and sexuality in particular have discussed, yet often faith has been overlooked in discussions of identity in writing center work (Denny, 2010). We propose that theories of race, gender, sexuality and other identities that have served as springboards for professional development in writing centers can help to facilitate the development of a greater literacy of faith and secularism as complicated and nuanced identities. Specifically, we believe theories involving intersectional social justice work and hybridity can help to facilitate self-reflective and productive interfaith dialogue or dialogue about faith and secularism. Thus, such theories can help writing center professionals dismantle stereotypes about believers and secularists and problematic notions of what faith, or a conversation about faith, is or should be

Possibilities for Interfaith Dialogue in Writing Centers and Programs

This article speaks into the pervasive silence on the subject of faith in writing center and writing program work. Through revisiting Sharon Crowley’s Toward a Civil Discourse and investigating silence, we encourage “counterfudamentalist work”: work that counters fundamentalist methodology by inviting fundamentalists and believers and nonbelievers of different kinds into nonliteralist and open-minded ways of reading writing-centered experiences involving religious faith and secularism. The three authors of this article offer personal narratives about their own experience with faith in their centers/programs and use different theoretical perspectives to start a necessary dialogue on faith and religious experiences. By interweaving theoretical perspectives, research, and personal narratives involving our WPA work, this article argues that writing center/program administrators must do the same, and we hope to model the types of conversations we must bring into our centers.University Writing Cente

The genetics of intellectual disability: advancing technology and gene editing [version 1; peer review: 2 approved]

Intellectual disability (ID) is a neurodevelopmental condition affecting 1–3% of the world’s population. Genetic factors play a key role causing the congenital limitations in intellectual functioning and adaptive behavior. The heterogeneity of ID makes it more challenging for genetic and clinical diagnosis, but the advent of large-scale genome sequencing projects in a trio approach has proven very effective. However, many variants are still difficult to interpret. A combined approach of next-generation sequencing and functional, electrophysiological, and bioinformatics analysis has identified new ways to understand the causes of ID and help to interpret novel ID-causing genes. This approach offers new targets for ID therapy and increases the efficiency of ID diagnosis. The most recent functional advancements and new gene editing techniques involving the use of CRISPR–Cas9 allow for targeted editing of DNA in in vitro and more effective mammalian and human tissue-derived disease models. The expansion of genomic analysis of ID patients in diverse and ancient populations can reveal rare novel disease-causing genes

Market Developments on Chinese International Air Passenger Markets in Light of COVID-19 Policy Measures

The world’s governments imposed a plethora of restrictions and quarantine rules to prevent the rapid spread of COVID-19. China was chosen for this study as it was the first market to be impacted. The overall aim of this paper was to analyse international air travel to and from China since the start of COVID-19 and to assess the impact of policy initiatives on seat capacity during this time. The key findings are that implementation of the so called Five one policy in March 2020 was associated with an almost immediate reduction in seat capacity on China to the rest of the world, partially suppressing the more typical impact of underlying GDP and air fares on capacity. It was further found that Chinese international gateways, as airports with substantial proportions of international and connecting traffic, remain the most distressed. Long haul international traffic and revenues from European and North American destinations all experienced unprecedented and sharp reductions. Traffic and revenues from other Asian markets was even more sporadic. Alarmingly, the study extracted that revenues from premium classes were deteriorating much faster than economy class, which is of imminent concern for long-haul carriers reliant on premium traffic coming into the pandemic

Determination of APTT factor sensitivity - the misguiding guideline.

INTRODUCTION: The Clinical and Laboratory Standards Institute (CLSI) has produced a guideline detailing how to determine the activated partial thromboplastin time's (APTT) sensitivity to clotting factor deficiencies, by mixing normal and deficient plasmas. Using the guideline, we determined the factor sensitivity of two APTT reagents. METHODS: APTTs were performed using Actin FS and Actin FSL on a Sysmex CS-5100 analyser. The quality of factor-deficient and reference plasmas from three commercial sources was assessed by assaying each of the clotting factors within the plasmas and by performing thrombin generation tests (TGT). RESULTS: Testing samples from 50 normal healthy subjects gave a two-standard deviation range of 21.8-29.2 s for Actin FS and 23.5-29.3 s for Actin FSL. The upper limits of these ranges were subsequently used to determine APTT factor sensitivity. Assay of factor levels within the deficient plasmas demonstrated that they were specifically deficient in a single factor, with most other factors in the range 50-150 iu/dL (Technoclone factor VII-deficient plasma has 26 iu/dL factor IX). APTTs performed on mixtures of normal and deficient plasmas gave diverse sensitivity to factor deficiencies dependent on the sources of deficient plasma. TGT studies on the deficient plasmas revealed that the potential to generate thrombin was not solely associated with the levels of their component clotting factors. CONCLUSION: Determination of APTT factor sensitivity in accordance with the CLSI guideline can give inconsistent and misleading results

Comparison of acquired activated protein C resistance, using the CAT and ST-genesia® analysers and three thrombin generation methods, in APS and SLE patients

Background: Acquired activated protein C resistance (APCr) has been identified in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Objective: To assess agreement between the ST-Genesia® and CAT analysers in identifying APCr prevalence in APS/SLE patients, using three thrombin generation (TG) methods. Methods: APCr was assessed with the ST- Genesia using STG-ThromboScreen and with the CAT using recombinant human activated protein C and Protac® in 105 APS, 53 SLE patients and 36 thrombotic controls. Agreement was expressed in % and by Cohenʹs kappa coefficient. Results: APCr values were consistently lower with the ST- Genesia® compared to the CAT, using either method, in both APS and SLE patients. Agreement between the two analysers in identifying APS and SLE patients with APCr was poor (≤65.9%, ≤0.20) or fair (≤68.5%, ≥0.29), regardless of TG method, respectively; no agreement was observed in thrombotic controls. APCr with both the ST Genesia and the CAT using Protac®, but not the CAT using rhAPC, was significantly greater in triple antiphospholipid antibody (aPL) APS patients compared to double/single aPL patients (p <0.04) and in thrombotic SLE patients compared to non-thrombotic SLE patients (p < 0.05). Notably, the ST-Genesia®, unlike the CAT, with either method, identified significantly greater APCr in pregnancy morbidity (median, confidence intervals; 36.9%, 21.9–49.0%) compared to thrombotic (45.7%, 39.6–55.5%) APS patients (p = 0.03). Conclusion: Despite the broadly similar methodology used by CAT and ST-Genesia®, agreement in APCr was poor/fair, with results not being interchangeable. This may reflect differences in the TG method, use of different reagents, and analyser data handling