Potentiation of neutrophil extracellular trap (NET) release is one mechanism by which antiphospholipid antibodies (aPL Abs) effect thrombotic events in patients with antiphospholipid syndrome (APS). Surface adenosine receptors trigger cyclic AMP (cAMP) formation in neutrophils, and this mechanism has been proposed to regulate NETosis in some contexts. Here we report that selective agonism of the adenosine A 2A receptor (CGS21680) suppresses aPL Ab-mediated NETosis in protein kinase A-dependent fashion. CGS21680 also reduces thrombosis in the inferior vena cavae of both control mice and mice administered aPL Abs. The antithrombotic medication dipyridamole is known to potentiate adenosine signaling by increasing extracellular concentrations of adenosine and interfering with the breakdown of cAMP. Like CGS21680, dipyridamole suppresses aPL Ab-mediated NETosis via the adenosine A 2A receptor and mitigates venous thrombosis in mice. In summary, these data suggest an anti-inflammatory therapeutic paradigm in APS, which may extend to thrombotic disease in the general population.

Abstract:The aim of this study was to use the World Health Organization (WHO) definition of anaemia to determine prevalence of anaemia among human immunodeficiency virus (HIV)-infected patients on the highly active antiretroviral therapy (HAART) and those that are HAART naive. Haemoglobin concentration was measured in 457 HIV patients consisting of 217 patients on HAART (86 males and 131 females) and 240 HAART naive patients (106 males and 134 females). According to WHO criteria, anaemia was defined as a haemoglobin concentration below 12g/dl in women and below 13g/dl in men. The anaemic HIV patients were further categorized according to WHO/ACTG anaemia toxicity grades. An overall anaemia prevalence of 60.61% was observed. The prevalence of anaemia was significantly higher among HAART naive patients (69.17%) than in HIV patients on HAART (51.15%) (P < 0.001). The prevalence of anaemia differ significantly (P < 0.05) between males and females of HAART naive patients with males (76.42%) having higher prevalence than females (63.43%). The WHO/ACTG categorization showed the same pattern between HIV patients on HAART and those that were HAART naive. Conclusively, the overall prevalence of anaemia was 60.61% among HIV patients. HAART naive patients have higher prevalence as well as males in this group. The WHO definition of anaemia is recommended as this will give the true prevalence of anaemia and allow for policy and interventions to address it. _______________________________________________________________________________________

Summary Murine models are widely used valuable tools to study deep vein thrombosis (VT). Leading experts in VT research came together through the American Venous Forum to develop a consensus on maximizing the utility and application of available mouse models of VT. In this work, we provide an algorithm for model selection, with discussion of the advantages, disadvantages, and applications of the main mouse models of VT. Additionally, we provide a detailed surgical description of the models with guidelines to validate surgical technique.

Murine models are widely used valuable tools to study deep vein thrombosis. Leading experts in venous thrombosis research came together through the American Venous Forum to develop a consensus on maximizing the utility and application of available mouse models of venous thrombosis. In this work, we provide an algorithm for model selection, with discussion of the advantages, disadvantages, and applications of the main mouse models of venous thrombosis. Additionally, we provide a detailed surgical description of the models with guidelines to validate surgical technique.

Essentials Three key updates are provided on the electrolytic inferior vena cava model (EIM).The originally described stimulator equipment has been discontinued; we developed an alternative.The fibrinolytic system and the current and time dependency of the EIM was characterized.EIM allows the investigation of the fibrinolytic system, critical for endovascular therapies. BackgroundThe electrolytic inferior vena cava model (EIM) is a murine venous thrombosis (VT) model that produces a non‐occlusive thrombus. The thrombus forms in the direction of blood flow, as observed in patients. The EIM is valuable for investigations of therapeutics due to the presence of continuous blood flow. However, the equipment used to induce thrombosis in the original model description was expensive and has since been discontinued. Further, the fibrinolytic system had not been previously studied in the EIM.ObjectivesWe aimed to provide an equipment alternative. Additionally, we further characterized the model through mapping the current and time dependency of thrombus resolution dynamics, and investigated the fibrinolytic system from acute to chronic VT.ResultsA voltage to current converter powered by a direct current power supply was constructed and validated, providing an added benefit of significantly reducing costs. The current and time dependency of thrombus volume dynamics was assessed by MRI, demonstrating the flexibility of the EIM to investigate both pro‐thrombotic and anti‐thrombotic conditions. Additionally, the fibrinolytic system was characterized in EIM. Centripetal distribution of plasminogen was observed over time, with peak staining at day 6 post thrombus induction. Both active circulating plasminogen activator inhibitor‐1 (PAI‐1) and vein wall gene expression of PAI‐1 peaked at day 2, coinciding with a relative decrease in tissue plasminogen activator and urokinase plasminogen activator.ConclusionsThe EIM is a valuable model of VT that can now be performed at low cost and may be beneficial in investigations of the fibrinolytic system.