Search

Direct Oral Anticoagulants (DOACs) have revolutionized the treatment of thromboembolic disorders, offering targeted, effective, and safer alternatives to traditional anticoagulants like heparins and vitamin K antagonists (VKAs). Despite their benefits, DOACs have drawbacks, including an increased risk of gastrointestinal bleeding and unsuitability for patients with mechanical heart valves. Recent research has highlighted Factor XI (FXI) as a promising anticoagulation target due to its significant role in pathological thrombosis and minor involvement in normal hemostasis. Abelacimab, an antibody that inhibits FXI, has shown potential in transforming anticoagulation therapy by sparing hemostasis. This review provides a comprehensive analysis of abelacimab, examining its clinical pharmacology and its pharmacokinetic and pharmacodynamic properties. It scrutinizes abelacimab's safety profile and key monitoring parameters. The current evidence supporting its use and potential future research strengthening its position in anticoagulant therapy is also discussed. The objective is to enhance understanding and contribute to discussions around developing safer anticoagulants, particularly for patients at risk for thrombosis.

Aims: Design and synthesis of a novel 3, 3′, 4′, 5, 7-O- pentasulfated Quercetin (QPS) as an activator of protein disulfide isomerase (PDI). Main Methods: Based on an in silico analysis we show that QPS binds to a and b domain of PDI (−7.4 kcal/mol) unlike PDI inhibitor quercetin 3-rutinoside (Q3R) that binds at substrate-binding domain b (−8.0 kcal/mol). QPS was synthesized and its structure validated using a combination of FTIR, NMR and mass spectral studies. Surprisingly, unlike Q3R QPS is shown to enhance the activity of purified recombinant PDI. Fluorometric and circular dichroism analysis showed that QPS binds to a unique site on PDI with marginal variations in its secondary structure. Key Findings: Hypersulfation of quercetin reverses its inhibitory effect on PDI as addition of exogenous PDI and QPS in human plasma showed increase in rate of coagulation, unlike Q3R which shows a decrease. Significance: The results indicate QPS to be a novel enhancer of PDI activity that can influence the coagulation rates in plasma. QPS has therapeutic potential to control bleeding.

The increasing prevalence of stroke, with an estimated annual cost of $71.5 billion, has made it a major health problem that increases disability and death, particularly in patients with atrial fibrillation. Although advanced age and atrial fibrillation are recognized as strong risk factors for stroke, the basis for this susceptibility are not well defined. Aging or associated diseases are accompanied by changes in rheostatic, humoral, metabolic and hemodynamic factors that may contribute more to stroke predisposition than rhythm abnormality alone. Several thromboembolism-predisposing clinical characteristics and serum biomarkers with prognostic significance have been identified in patients with atrial fibrillation. Although anticoagulation decreases the risk of thromboembolism, management in the elderly remains complex due to major concerns about bleeding. New anticoagulants and nonpharmacologic strategies are helpful to reduce the risk of bleeding, particularly in older-elderly patients. Herein, we review the pathogenesis and management of select issues of thromboembolism in the elderly with atrial fibrillation.