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2.
J Am Heart Assoc ; 6(7)2017 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-28673898

RESUMEN

BACKGROUND: Coagulation factor V (FV) plays a key role in hemostasis, is present in plasma and platelets, and has both pro- and anticoagulant properties; however, the contribution of platelet-derived FV to arterial thrombosis remains undetermined. METHODS AND RESULTS: Using transgenic mice with various levels of FV gene expression that was restricted to the plasma or platelets, the roles of platelet FV were evaluated in the regulation of arterial thrombosis and platelet activation. Mice with higher levels of platelet FV exhibited faster thrombotic occlusion of the carotid artery after injury compared with mice with lower platelet FV levels. Infusion of platelets with higher levels of FV into transgenic mice with undetectable levels of platelet FV reduced the time to carotid artery occlusion. In contrast, infusion of purified recombinant plasma FV into mice with undetectable platelet FV levels failed to reduce the carotid occlusion times following injury. Evaluation of isolated platelets revealed that platelet-derived FV was critical for the regulation of platelet activation. These effects were associated with an increased level of expression of P-selectin and increased cGMP in platelets. CONCLUSIONS: We established that platelet-derived FV is a critical mediator of arterial thrombosis that involves platelet activation.


Asunto(s)
Coagulación Sanguínea , Plaquetas/metabolismo , Enfermedades de las Arterias Carótidas/sangre , Factor V/metabolismo , Activación Plaquetaria , Trombosis/sangre , Animales , Coagulación Sanguínea/efectos de los fármacos , Coagulación Sanguínea/genética , Plaquetas/efectos de los fármacos , Enfermedades de las Arterias Carótidas/genética , GMP Cíclico/sangre , Modelos Animales de Enfermedad , Factor V/administración & dosificación , Factor V/genética , Predisposición Genética a la Enfermedad , Infusiones Intravenosas , Masculino , Ratones Noqueados , Fenotipo , Activación Plaquetaria/efectos de los fármacos , Activación Plaquetaria/genética , Proteínas Recombinantes/administración & dosificación , Selenoproteína P/sangre , Trombosis/genética , Factores de Tiempo , Factor de Crecimiento Transformador beta
3.
Haemophilia ; 18(3): e286-9, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-21910789

RESUMEN

It is well known and often reported that patients with long-term health conditions have problems adhering to treatment regimens. This is often reportedly worst in adolescents who struggle with the physical and psychological impact of adolescence as well as with the limitations that treatment regimens impose on their day-to-day activities. This article presents results from a larger study that aimed to discover what living with haemophilia in the 21st century was like for boys with severe haemophilia. The overall study was a multi-method, cross-sectional interview based study of 30 boys with severe haemophilia, treated with prophylaxis at a single site in the UK. Although not specifically asked in the interview schedule, opinions about treatment (prophylaxis) were given by 66% of the boys. These boys recognized that prophylaxis offered them protection from bleeding, the older and more sporty boys understood the need for tailored prophylaxis around 'risk' activities such as sport or events away from home. For some boys this meant low dose daily prophylaxis, and this further enhanced treatment adherence, as it became firmly embedded in their daily ritual of health care. This study shows that adolescent boys are in fact adherent with treatment, possibly at a schedule decided upon by them rather than one directed by the haemophilia centre. They are able to comprehend complex treatment decisions and make treatment plans that offer them maximum protection with minimal interference in their day-to-day activities.


Asunto(s)
Coagulantes/administración & dosificación , Factor V/administración & dosificación , Hemofilia A/tratamiento farmacológico , Hemofilia B/tratamiento farmacológico , Adolescente , Actitud Frente a la Salud , Estudios Transversales , Esquema de Medicación , Hemofilia A/psicología , Hemofilia B/psicología , Humanos , Masculino , Cumplimiento de la Medicación/psicología , Investigación Cualitativa , Calidad de Vida , Reino Unido
4.
Haemophilia ; 17(1): 70-4, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20579111

RESUMEN

The most common bleeding in haemophilic patients is in joints, and joint disability is the most common complications in these patients receiving inadequate treatment. Limited by economy and inadequate treatment, developing countries face huge challenge to reduce disability and improve quality of life (QoL) of haemophilic children. The aim of this study was to investigate the effect of low dose secondary prophylaxis in China. Children with moderate and severe haemophilia from the Beijing Children Hospital, Beijing, China, and with established joint disease, were followed for a 12-week observation period followed by a 12-week low dose secondary prophylaxis-study period (for haemophilia A, factor VIII concentrate 10 IU kg(-1) twice weekly; for haemophilia B, factor IX concentrate 20 IU kg(-1) weekly). The reduction of joint bleeding, improvement of joint function and QoL during prophylaxis were analysed. In total 34 children (median age 7.8 years) were analyzable. The number of joint bleeds decreased from a total of 337 (individual range 3-24, mean 9.9) during the observation period to 57 (range 0-6, mean 1.7) during the study period with an overall of reduction 83%. Joint function improved in 66.7% of disease joints, with 23.2% of which were considered good to moderate. School attendance improved in all subjects, sports participation and daily activity improved moderately. Low dose secondary prophylaxis significantly reduces frequency of joint bleeding; with moderate improvement in joint function, school attendance, sport participation and daily activities. Low dose secondary prophylaxis is therefore, cost-effective as applied to developing countries such as China, although there are still unresolved issues.


Asunto(s)
Factor IX/uso terapéutico , Factor V/uso terapéutico , Hemartrosis/prevención & control , Hemofilia A/tratamiento farmacológico , Hemofilia B/tratamiento farmacológico , Adolescente , Niño , Preescolar , China , Países en Desarrollo , Factor IX/administración & dosificación , Factor V/administración & dosificación , Femenino , Hemartrosis/etiología , Hemofilia A/complicaciones , Hemofilia B/complicaciones , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Proyectos Piloto
6.
Arterioscler Thromb Vasc Biol ; 26(12): 2807-12, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16973976

RESUMEN

BACKGROUND: Joint exposure to oral conjugated equine estrogen (CEE) and prothrombotic genetic variants factor II G20210A or factor V G1601A (Leiden) increase venous thrombotic risk 6- to 16-fold in postmenopausal women. Esterified estrogen (EE), an alternative estrogenic compound, appears not to be associated with increased risk and nothing is known about the joint risk with prothrombotic genetic variants. METHODS AND RESULTS: We conducted a population-based, case-control study among postmenopausal women within a health maintenance organization. Subjects included 328 cases who sustained a first venous thrombosis and 1591 controls. Current hormone use was defined using electronic pharmacy records and variants FII G20210A and FV Leiden were genotyped using blood samples. FII and FV Leiden variants were associated with 2.1-fold and 3.7-fold increases in venous thrombotic risk, respectively. Overall, CEE use was associated with a 2.5-fold increase in risk compared with no hormone use, whereas EE use was not associated with a statistically increased risk. Compared with no hormone use and no variant, joint exposure to CEE and either prothrombotic variant was associated with an odds ratio (OR) of 9.1 (95% CI: 4.5 to 18.2), whereas joint exposure to EE and either variant was associated with an OR of 2.1 (0.6 to 6.8). When analyses were restricted to hormone users with either variant, CEE use was associated with an OR of 5.3 (1.3 to 21.7) compared with EE use. CONCLUSIONS: These findings need replication and suggest EE use is associated with less risk than CEE use especially among 5% to 10% of women who are carriers of a prothrombotic variant.


Asunto(s)
Estrógenos Conjugados (USP)/efectos adversos , Estrógenos Esterificados (USP)/efectos adversos , Factor V/efectos adversos , Posmenopausia/fisiología , Protrombina/efectos adversos , Trombosis de la Vena/etiología , Administración Cutánea , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Terapia de Reemplazo de Estrógeno , Estrógenos Conjugados (USP)/administración & dosificación , Estrógenos Esterificados (USP)/administración & dosificación , Factor V/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Posmenopausia/metabolismo , Protrombina/administración & dosificación , Factores de Riesgo , Trombosis de la Vena/fisiopatología
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