RESUMEN
INTRODUCTION: von Willebrand disease (VWD) is the most common inherited bleeding disorder known in humans. Currently, studies investigating the health-related quality of life (HR-QoL) in VWD using standardized tools are limited, particularly among patients with mild decreases in von Willebrand factor or activity. AIM: To determine HR-QoL and its predictors among patients with mild, moderate and severe forms of VWD. METHODS: Patients with clinical diagnosis of VWD were recruited from a tertiary Inherited Bleeding Disorder Clinic. Upon informed consent, bleeding scores were obtained via a standardized, self-administered tool. Each participant also completed a HR-QoL questionnaire (SF-36). Analyses included paired t-test, independent t-test, one-way anova and multivariate regression. RESULTS: A total of 102 patients were recruited (consent rate = 95%). Participants were 38 years on average (SD 14.8), 78% were female and 80% were diagnosed with VWD Type 1. Compared to age- and sex-matched normative data, VWD patients had clinically and statistically significant reductions in seven of eight HR-QoL domains and the physical and mental component summaries. Adjusted for age, sex, socioeconomic status and rurality, there was a trend towards lower physical component summary with increasing bleeding score, and lower mental domains with iron deficiency status (P = 0.07 and P = 0.08 respectively). CONCLUSION: This study is the first to examine the impact of VWD on HR-QoL across disease severity while incorporating socioeconomic status and rurality. Significant reductions in HR-QoL among VWD patients, especially the relationship between iron status and mental HR-QoL, strengthen the rationale for prospective studies to evaluate the efficacy of iron replacement in this setting.
Asunto(s)
Hierro/metabolismo , Enfermedades de von Willebrand/diagnóstico , Adulto , Estudios Transversales , Femenino , Hemorragia , Humanos , Masculino , Calidad de VidaRESUMEN
INTRODUCTION/AIM: Our aim was to generate, optimize and validate a self-administered bleeding assessment tool (self-BAT) for von Willebrand disease (VWD). METHODS: In Phase 1, medical terminology in the expert-administered International Society on Thrombosis and Haemostasis (ISTH)-BAT was converted into a Grade 4 reading level to produce the first version of the Self-BAT which was then optimized to ensure agreement with the ISTH-BAT. In Phase 2, the normal range of bleeding scores (BSs) was determined and test-retest reliability analysed. In Phase 3, the optimized Self-BAT was tested as a screening tool for first time referrals to the Haematology clinic. RESULTS: Bleeding score from the final optimized version of the Self-BAT showed an excellent intra-class correlation coefficient (ICC) of 0.87 with ISTH-BAT BS in Phase 1. In Phase 2, the normal range of BSs for the optimized Self-BAT was determined to be 0 to +5 for females and 0 to +3 for males and excellent test-retest reliability was shown (ICC = 0.95). In Phase 3, we showed that a positive Self-BAT BS (≥6 for females, ≥4 for males) has a sensitivity of 78%, specificity of 23%, positive predictive value (PPV) of 0.15 and negative predictive value (NPV) of 0.86 for VWD; these figures improved when just the females were analysed; sensitivity of 100%, specificity of 21%, PPV = 0.17 and NPV = 1.0. CONCLUSION: We show an optimized Self-BAT can generate comparable BS to the expert-administered ISTH-BAT and is a reliable, effective screening tool to incorporate into the assessment of individuals, particularly women, referred for a possible bleeding disorder.
Asunto(s)
Hemorragia/diagnóstico , Tamizaje Masivo , Autoadministración , Enfermedades de von Willebrand/diagnóstico , Adolescente , Adulto , Anciano , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Bleeding Assessment Tools (BATs) have been developed to aid in the standardized evaluation of bleeding symptoms. The Vicenza Bleeding Questionnaire (BQ), published in 2005, established a common framework and scoring key that has undergone subsequent modification over the years, culminating in the publication of the ISTH-BAT in 2010. Understanding the normal range of bleeding scores is critical when assessing the utility of a BAT. Within the context of The Merging Project, a bioinformatics system was created to facilitate the merging of legacy data derived from four different (but all Vicenza-based) BATs; the MCMDM1-VWD BQ, the Condensed MCMDM-1VWD BQ, the Pediatric Bleeding Questionnaire and the ISTH-BAT. Data from 1040 normal adults and 328 children were included in the final analysis, which showed that the normal range is 0-3 for adult males, 0-5 for adult females and 0-2 in children for both males and females. Therefore, the cut-off for a positive or abnormal BS is ≥4 in adult males, ≥6 in adult females and ≥3 in children. This information can now be used to objectively assess bleeding symptoms as normal or abnormal in future studies.
Asunto(s)
Hemorragia/sangre , Hemorragia/diagnóstico , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Biología Computacional/métodos , Femenino , Hemofilia A/sangre , Hemofilia A/diagnóstico , Hemorragia/etiología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Valores de Referencia , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Adulto Joven , Enfermedades de von Willebrand/sangre , Enfermedades de von Willebrand/diagnósticoRESUMEN
Essentials Type 2N von Willebrand disease involves impaired von Willebrand factor to factor VIII binding. Type 2N von Willebrand disease mutations exhibit qualitative and mild quantitative deficiencies. Type 2N von Willebrand disease mice exhibit unstable venous hemostatic thrombi. The factor VIII-binding ability of von Willebrand factor regulates arteriole thrombosis dynamics. SUMMARY: Background von Willebrand factor (VWF) and factor VIII (FVIII) circulate as a non-covalent complex, with VWF serving as the carrier for FVIII. VWF indirectly influences secondary hemostasis by stabilizing FVIII and transporting it to the site of primary hemostasis. Type 2N von Willebrand disease involves impaired binding of VWF to FVIII, resulting in decreased plasma levels of FVIII. Objectives In these studies, we characterize the impact of three type 2N VWD variants (R763A, R854Q, R816W) on VWF secretion, FVIII stabilization and thrombus formation in a murine model. Methods Type 2N VWD mice were generated by hydrodynamic injections of mutant murine VWF cDNAs and the influence of these variants on VWF secretion and FVIII binding was evaluated. In vivo hemostasis and the dynamics of thrombus formation and embolization were assessed using a murine tail vein transection hemostasis model and an intravital thrombosis model in the cremaster arterioles. Results Type 2N VWD variants were associated with decreased VWF secretion using cell and animal-based models. FVIII-binding to type 2N variants was impaired in vitro and was variably stabilized in vivo by expressed or infused 2N variant VWF protein. Both transgenic type 2N VWD and FVIII knockout (KO) mice demonstrated impaired thrombus formation associated with decreased thrombus stability. Conclusions The type 2N VWD phenotype can be recapitulated in a murine model and is associated with both quantitative and qualitative VWF deficiencies and impaired thrombus formation. Patients with type 2N VWD may have normal primary hemostasis formation but decreased thrombus stability related to ineffective secondary hemostasis.
Asunto(s)
Factor VIII/metabolismo , Hemostasis , Trombosis/sangre , Enfermedad de von Willebrand Tipo 2/sangre , Factor de von Willebrand/metabolismo , Animales , Modelos Animales de Enfermedad , Factor VIII/genética , Células HEK293 , Hemostasis/genética , Humanos , Cinética , Ratones Endogámicos C57BL , Ratones Noqueados , Unión Proteica , Estabilidad Proteica , Trombosis/genética , Transfección , Enfermedad de von Willebrand Tipo 2/genética , Factor de von Willebrand/genéticaRESUMEN
Breeding experiments were conducted on cats with congenital taillessness, to test the dissemination pattern of taillessness in their offspring. Clinical evaluation, radiographic analysis of the vertebral column and histological studies of the digestive tract and central nervous tissue were conducted to determine the association of malformations of these systems in cats born with different degrees of taillessness noted in the rumpy and stumpy cats. The mode of transmission of the tailless (Manx) condition assumed to be through an autosomal dominant factor (M) was confirmed by this investigation. It is hypothesized that the problems associated with the tailless condition such as spina bifida, urinary and faecal incontinence and locomotor disturbances of the pelvic limbs may all be related to a disturbance affecting the development of the central nervous system in the early embryonic life.
Asunto(s)
Enfermedades de los Gatos/congénito , Cola (estructura animal)/anomalías , Animales , Cruzamiento , Enfermedades de los Gatos/embriología , Enfermedades de los Gatos/genética , Enfermedades de los Gatos/patología , Gatos , Femenino , Masculino , Espina Bífida Oculta/embriología , Espina Bífida Oculta/veterinaria , Médula Espinal/embriología , Médula Espinal/patología , Cola (estructura animal)/embriologíaRESUMEN
BACKGROUND: Type 3 von Willebrand disease (VWD) is the most severe form of the disease and is classically inherited in an autosomal recessive fashion. OBJECTIVES: The aim of the current study was to investigate the molecular pathogenesis of a Canadian cohort of type 3 VWD patients. PATIENTS AND METHODS: Thirty-four families comprised of 100 individuals were investigated. Phenotypic data, including bleeding scores (BS), von Willebrand factor (VWF) laboratory values and anti-VWF inhibitor status were included as well as sequence analysis. RESULTS: We identified 31 different mutations (20 novel): 8 frameshift, 5 splice site, 9 nonsense, 1 gene conversion, 6 missense and 2 partial gene deletion mutations. The majority of mutations identified were in the propeptide (42%); index cases (IC) with these mutations exhibited more severe bleeding (BS = 22) than those with mutations elsewhere in VWF (BS = 13). Sixty-two out of 68 (91%) mutant alleles were identified. Twenty-nine IC (85%) had a VWF null genotype identified; 17 homozygous, 12 compound heterozygous. In five IC (15%), two mutant VWF alleles were not identified to explain the type 3 VWD phenotype. In four ICs only one mutant VWF allele was identified and in one IC no mutant VWF alleles were identified. CONCLUSIONS: We have investigated the molecular pathogenesis of a Canadian cohort of type 3 VWD patients. Obligate carriers are not phenotypically silent in the Canadian population; 48% have been diagnosed with type 1 VWD. In approximately 50% of families in this study the inheritance pattern for type 3 VWD is co-dominant and not recessive.
Asunto(s)
Coagulación Sanguínea/genética , Genes Dominantes , Mutación , Enfermedad de von Willebrand Tipo 3/genética , Factor de von Willebrand/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Canadá/epidemiología , Niño , Preescolar , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Células HEK293 , Herencia , Heterocigoto , Homocigoto , Humanos , Lactante , Isoanticuerpos/sangre , Masculino , Persona de Mediana Edad , Fenotipo , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Transfección , Adulto Joven , Enfermedad de von Willebrand Tipo 3/sangre , Enfermedad de von Willebrand Tipo 3/diagnóstico , Enfermedad de von Willebrand Tipo 3/epidemiología , Factor de von Willebrand/inmunología , Factor de von Willebrand/metabolismoAsunto(s)
Automóviles , Seguridad , Accidentes de Tránsito/prevención & control , Niño , Preescolar , Humanos , Proyectos Piloto , Equipos de SeguridadRESUMEN
Many hospital executives make typical errors in managing Hispanic employees. See how making some simple adjustments to management style to respect their cultural heritage can make a difference in performance.
Asunto(s)
Hispánicos o Latinos , Administración de Personal en Hospitales/métodos , Características Culturales , Sudeste de Estados Unidos , Sudoeste de Estados UnidosRESUMEN
The program described enabled St. Mary's Hospital to recruit individuals with pre-requisite knowledge in anatomy, pathophysiology and medical terminology and then have them receive comprehensive training in ICD-9-CM coding which addressed the unique demands imposed by the medical record department and the PRO. In this way, the department's immediate and future needs for coders appears to have been satisfied. An evaluation on the success of this training program will be assessed in three months and reported upon at that time.
Asunto(s)
Indización y Redacción de Resúmenes/educación , Enfermedad/clasificación , Departamentos de Hospitales , Capacitación en Servicio , Servicio de Registros Médicos en Hospital , Curriculum , Hospitales con 300 a 499 Camas , Humanos , Admisión y Programación de Personal , Virginia , Recursos HumanosRESUMEN
A storage disease in a 2-year-old Japanese Spaniel resembled a GM2 gangliosidosis previously identified in a now extinct line of German Shorthaired Pointers. Despite a later appearance of signs in the Japanese Spaniel, the distribution, staining, and ultrastructure of the stored material were similar in the two breeds. Golgi studies of cerebral cortical neurons revealed the formation of spiny and aspiny enlargements at the axon hillock region (meganeurites) and the growth of secondary neurites from this region. As in the German Shorthaired Pointer model, there was massive storage of GM2 ganglioside as well as a seemingly paradoxical increase in total beta-hexosaminidase activity measured in vitro.