Therapeutic anticoagulation is indicated for a variety of circumstances and conditions in several fields of medicine to prevent or treat venous and arterial thromboembolism. According to the different mechanisms of action, the available parenteral and oral anticoagulant drugs share the common principle of hampering or blocking key steps of the coagulation cascade, which unavoidably comes at the price of an increased propensity to bleed. Hemorrhagic complications affect patient prognosis both directly and indirectly (ie, by preventing the adoption of an effective antithrombotic strategy). Inhibition of factor XI (FXI) has emerged as a strategy with the potential to uncouple the pharmacological effect and the adverse events of anticoagulant therapy. This observation is based on the differential contribution of FXI to thrombus amplification, in which it plays a major role, and hemostasis, in which it plays an ancillary role in final clot consolidation. Several agents were developed to inhibit FXI at different stages (ie, suppressing biosynthesis, preventing zymogen activation, or impeding the biological action of the active form), including antisense oligonucleotides, monoclonal antibodies, small synthetic molecules, natural peptides, and aptamers. Phase 2 studies of different classes of FXI inhibitors in orthopedic surgery suggested that dose-dependent reductions in thrombotic complications are not paralleled by dose-dependent increases in bleeding compared with low-molecular-weight heparin. Likewise, the FXI inhibitor asundexian was associated with lower rates of bleeding compared with the activated factor X inhibitor apixaban in patients with atrial fibrillation, although no evidence of a therapeutic effect on stroke prevention is available so far. FXI inhibition could also be appealing for patients with other conditions, including end-stage renal disease, noncardioembolic stroke, or acute myocardial infarction, for which other phase 2 studies have been conducted. The balance between thromboprophylaxis and bleeding achieved by FXI inhibitors needs confirmation in large-scale phase 3 clinical trials powered for clinical end points. Several of such trials are ongoing or planned to define the role of FXI inhibitors in clinical practice and to clarify which FXI inhibitor may be most suited for each clinical indication. This article reviews the rationale, pharmacology, results of medium or small phase 2 studies, and future perspectives of drugs inhibiting FXI.

No abstract

Background: The optimal antithrombotic regimen for patients with atrial fibrillation (AF) and chronic coronary syndromes beyond 1 year after percutaneous coronary intervention (PCI) is a matter of debate. For these patients, guidelines recommend oral anticoagulation (OAC) alone, but the risk of thrombotic complications remains a concern. The aim of this study was to characterize the incidence, presentation and use of antithrombotic therapy in patients with AF, prior stenting > 12 months and new ST-segment elevation myocardial infarction (STEMI). Methods: Consecutive patients were selected from an institutional registry over a 3-year period if they matched the following criteria: 1) STEMI undergoing primary PCI; 2) AF; 3) chronic coronary syndrome with prior stenting > 12 months. Results: Among 852 consecutive STEMI patients undergoing primary PCI, the prevalence of AF was 4.1%, and 6 (0.9%) patients met all the inclusion criteria. Substantial heterogeneity in antithrombotic treatment for these patients was noted (e.g., OAC alone, OAC plus a single antiplatelet agent, no antithrombotic therapy). In 50% of patients, the STEMI episode was linked to a previously stented lesion or documented plaque. Conclusions: This case review illustrates the wide heterogeneity in antithrombotic pharmacotherapy among AF patients presenting with STEMI > 12 months after PCI. The underlying reason for STEMI is only partly related to disease progression or stent-related events. This finding suggests that multiple mechanisms of recurrence may be advocated, and are not only limited to antithrombotic therapy but may be explained by the natural history of coronary artery disease in remote vessels. (Cardiol J 2020; 27, 1: 8-15)

Timely administration of good-quality colostrum represents the first farm strategy to avoid the failure of passive transfer (FPT). However, calves born during the night are likely to be fed later than recommended. Our aim was to evaluate whether night-occurring calving and delayed first milking affected colostrum quality and immune passive transfer. The dataset included 463 calvings. Four liters of colostrum were administered by an esophageal tube feeder. The mean Brix% of colostrum was 27.43%, while serum Brix% at two days of life in calves was 10.19%. According to the Generalized Linear Model, parity ≥ 4, calving months of March, April, and from September to November positively influenced the quality of colostrum. Dams carrying a male calf produced lower quality colostrum compared with those carrying a female calf (−2.78 ± 1.04 % Brix, p = 0.008); heavier female calves were associated with greater colostrum quality (0.29 ± 0.05 for each Kg increase, p < 0.001). Night- or day-calving had no effect on the quality of colostrum. The only factor influencing the serum Brix% of female Holstein calves at two days of life was the day- or night-occurring birth (−0.386 ± 0.188 Brix% in calves born during the night, p = 0.04). Our results showed that calves born overnight and fed the day after had decreased serum Total Protein concentrations as indicated by reduced Brix refractometer readings, compared with calves born during the day and fed quickly after birth. However, the administration of 4 L of high-quality colostrum likely improved their serum Brix% at two days of life. Alternatively, where the prevalence of good-quality colostrum is lower, improving calving supervision and ensuring timely feeding are important to reduce the risk of FPT.