Transcriptomic Analysis of Extracellular Vesicles in the Search for Novel Plasma and Thrombus Biomarkers of Ischemic Stroke Etiologies.

Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision. We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) to identify potential biomarkers of IS etiologies. The proteins encoded by the selected genes were measured in the sera of IS patients (n = 114) and in hypertensive patients with (n = 78) and without atrial fibrillation (AF) (n = 20). IGFBP-2, the most promising candidate, was studied using immunohistochemistry in the IS thrombi (n = 23) and atrium of AF patients (n = 13). In vitro, the IGFBP-2 blockade was analyzed using thromboelastometry and endothelial cell cultures. We identified 745 differentially expressed genes among EVs of cardioembolic, atherothrombotic, and ESUS groups. From these, IGFBP-2 (cutoff > 247.6 ng/mL) emerged as a potential circulating biomarker of embolic IS [OR = 8.70 (1.84-41.13) p = 0.003], which was increased in patients with AF vs. controls (p < 0.001) and was augmented in cardioembolic vs. atherothrombotic thrombi (p < 0.01). Ex vivo, the blockage of IGFBP-2 reduced clot firmness (p < 0.01) and lysis time (p < 0.001) and in vitro, diminished endothelial permeability (p < 0.05) and transmigration (p = 0.06). IGFBP-2 could be a biomarker of embolic IS and a new therapeutic target involved in clot formation and endothelial dysfunction.

Recommendations for the Clinical Approach to Immune Thrombocytopenia: Spanish ITP Working Group (GEPTI).

Primary immune thrombocytopenia (ITP) is a complex autoimmune disease whose hallmark is a deregulation of cellular and humoral immunity leading to increased destruction and reduced production of platelets. The heterogeneity of presentation and clinical course hampers personalized approaches for diagnosis and management. In 2021, the Spanish ITP Group (GEPTI) of the Spanish Society of Hematology and Hemotherapy (SEHH) updated a consensus document that had been launched in 2011. The updated guidelines have been the reference for the diagnosis and management of primary ITP in Spain ever since. Nevertheless, the emergence of new tools and strategies makes it advisable to review them again. For this reason, we have updated the main recommendations appropriately. Our aim is to provide a practical tool to facilitate the integral management of all aspects of primary ITP management.

Security profile of direct anticoagulants. Preferred use in atrial fibrillation. / Perfil de seguridad de los anticoagulantes directos. Uso preferente en fibrilación auricular.

A multidisciplinary panel of cardiologists, neurologists, internal medicine and specialists in hemostasis and thrombosis has elaborated this document showing recent scientific evidences supporting a better profile of direct oral anticoagulants (DOACs) versus vitaminK antagonists (VKA), as well as the indications of specific antidotes and hemostatic agents to reverse the anticoagulant effects of DOACs. The analysis reinforces the best profile of DOACs and its special benefit in patients with basal high hemorrhagic risk.

Topical issues in venous thromboembolism.

Despite clear guidelines and the availability of effective treatments, venous thromboembolism (VTE) remains relatively common, particularly in the hospital setting. This paper reviews topical issues in VTE, in terms of treatments, data and guidelines. Existing anticoagulants have several limitations. Bleeding risk is a concern with all anticoagulants. Vitamin K antagonists are the mainstay of oral anticoagulant therapy, but they are limited by the need for frequent monitoring. Unfractionated heparin (UFH) is limited by an inconvenient route of administration (continuous intravenous infusion) and a higher risk of heparin-induced thrombocytopenia and bleeding compared with low molecular weight heparins (LMWH). LMWH have a more predictable pharmacokinetic profile and greater bioavailability than UFH, which permits weight-adjusted LMWH dosing without the need for monitoring in most patients. LMWH also have a more convenient dosing strategy than UFH (once-daily subcutaneous injection). Fondaparinux is a selective inhibitor of factor Xa and, like LMWH, does not require monitoring. The efficacy of fondaparinux in long-term VTE treatment remains to be established. The optimal time to initiate thromboprophylaxis in patients undergoing orthopaedic surgery remains controversial. Initiating thromboprophylaxis just before or soon after surgery (the 'just-in-time' strategy) achieves better thromboprophylaxis but could increase the risk of bleeding complications. Balancing the need for extended thromboprophylaxis after major surgery with the need to minimize bleeding remains an important consideration. Despite clear guidelines, thromboprophylaxis is widely underused, particularly in medical patients, in whom rates as low as 28% have been reported. Electronic alert systems may be of value for increasing the use of adequate thromboprophylaxis. The use of different definitions of VTE and bleeding in clinical trials, together with missing venography data, conflicting guidelines in patients undergoing total hip or knee arthroplasty, and the limited amount of data in children, also make VTE prevention and management more difficult. Administering thromboprophylaxis to a wider group of patients, employing the 'just-in-time' protocols, ensuring adequate duration of thromboprophylaxis, combining different methods of thromboprophylaxis and developing new anticoagulants should help to improve thromboprophylaxis.

Impact of surgery and chemotherapy on von Willebrand factor and vascular endothelial growth factor levels in colorectal cancer.

INTRODUCTION: von Willebrand factor (vWf) is thought to mediate binding of tumour cells to platelets and to favour their systemic spreading capacity. Platelets involved in tumour angiogenesis are capable of releasing vascular endothelial growth factor (VEGF). Hence, levels of vWf and VEGF may correlate with cancer stage. The objectives are determine the impact of surgery and chemotherapy on vWf and VEGF in colorectal cancer (CRC) patients. MATERIAL AND METHODS: Twenty healthy volunteers (group 1), 14 patients with locally advanced CRC (group 2) and 12 patients with metastatic CRC (group 3) were enrolled. Blood samples were taken at recruitment in group 1, and before and after surgery and chemotherapy in groups 2 and 3, respectively. Blood levels of vWf, VEGF, platelet count, C-reactive protein (CRP), ceruloplasmin and carcinoembrionary antigen (CEA) were measured. RESULTS: At baseline, group 3 showed higher concentrations of vWf than the other groups (p<0.05). In group 2, vWf became elevated 40% post-surgery (p=0.016), independently of changes in CRP or ceruloplasmin. In group 3, chemotherapy caused a 42% reduction in VEGF (p=0.015). CONCLUSIONS: There was a strong correlation between higher vWf levels and more advanced CRC stage at diagnosis. These levels were elevated post-surgery in patients with locally advanced CRC. Chemotherapy significantly decreased VEGF in metastatic CRC patients before CEA showed any significant change.