RESUMEN
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.
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Biomarcadores , Vesículas Extracelulares , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina , Accidente Cerebrovascular Isquémico , Trombosis , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Biomarcadores/sangre , Masculino , Femenino , Anciano , Trombosis/metabolismo , Trombosis/etiología , Trombosis/sangre , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/genética , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Persona de Mediana Edad , Perfilación de la Expresión Génica , Transcriptoma , Fibrilación Atrial/metabolismo , Fibrilación Atrial/genética , Fibrilación Atrial/complicaciones , Fibrilación Atrial/sangreRESUMEN
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.
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Se presenta un trabajo multidisciplinar realizado por especialistas de Cardiología, Hemostasia y Trombosis, Medicina Interna y Neurología en el que se exponen las evidencias científicas actuales que demuestran el mejor perfil de seguridad de los anticoagulantes orales de acción directa (ACOD) frente a los antivitamina K (AVK) y se discuten indicaciones y el papel de los antídotos específicos y hemostáticos para la reversión del efecto anticoagulante. El análisis sugiere que el mejor perfil de seguridad de los ACOD los hace especialmente útiles en pacientes con alto riesgo hemorrágico
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 vitamin K 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
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Humanos , Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Medidas de Seguridad , Warfarina/uso terapéutico , Anticoagulantes/metabolismo , Anticoagulantes/farmacología , Hemorragias Intracraneales , Hemorragia Gastrointestinal , Accidente Cerebrovascular/prevención & control , Administración OralRESUMEN
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.
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Antitrombinas/efectos adversos , Fibrilación Atrial/complicaciones , Hemorragia/prevención & control , Accidente Cerebrovascular/prevención & control , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Antídotos/uso terapéutico , Antitrombinas/uso terapéutico , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/prevención & control , Hemorragia Cerebral/terapia , Dabigatrán/efectos adversos , Dabigatrán/uso terapéutico , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/terapia , Hemorragia/inducido químicamente , Hemorragia/etiología , Hemorragia/terapia , Humanos , Guías de Práctica Clínica como Asunto , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Piridinas/efectos adversos , Piridinas/uso terapéutico , Piridonas/efectos adversos , Piridonas/uso terapéutico , Factores de Riesgo , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Accidente Cerebrovascular/etiología , Tiazoles/efectos adversos , Tiazoles/uso terapéuticoRESUMEN
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Humanos , Ácido Tranexámico/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Premedicación/métodosAsunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Pérdida de Sangre Quirúrgica/prevención & control , Hemostáticos/uso terapéutico , Ácido Tranexámico/uso terapéutico , Análisis Costo-Beneficio , Fibrinólisis/efectos de los fármacos , Hemostáticos/administración & dosificación , Hemostáticos/efectos adversos , Hemostáticos/economía , Hemostáticos/farmacología , Humanos , Infusiones Intravenosas , Metaanálisis como Asunto , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Trombosis/inducido químicamente , Ácido Tranexámico/administración & dosificación , Ácido Tranexámico/efectos adversos , Ácido Tranexámico/economía , Ácido Tranexámico/farmacología , Reacción a la TransfusiónRESUMEN
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.
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Tromboembolia Venosa , Adulto , Anticoagulantes/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Niño , Alarmas Clínicas , Monitoreo de Drogas , Humanos , Guías de Práctica Clínica como Asunto , Sociedades Médicas , Estados Unidos , Tromboembolia Venosa/complicaciones , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & controlRESUMEN
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.
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Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/terapia , Factor A de Crecimiento Endotelial Vascular/sangre , Factor de von Willebrand/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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
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