Análisis del switch guiado por farmacocinética de factores VIII de semivida estándar a factores de semivida extendida

CO-170 Introducción y objetivos: Los factores VIII (FVIII) de semivida extendida (EHL) han mostrado en los ensayos clínicos mejoras de al menos 1, 3 veces la semivida plasmática (t1/2) y 1, 25 veces el área bajo la curva (AUC) respecto a los FVIII estándar (SHL). Herramientas basadas en modelos farmacocinéticos (PK) poblacionales permiten estimar los parámetros PK individuales y ajustar la profilaxis. El objetivo de este estudio es analizar el switch PK-guiado de SHL a EHL en pacientes con hemofilia A (HA). Métodos: Estudio multicéntrico comparativo, cruzado, prospectivo que analiza las diferencias PK tras el cambio de factores SHL a EHL (Elocta® y Adynovi®) en pacientes con HA grave/moderada en profilaxis. Se ha empleado el PopPK WAPPS-Hemo® con 2-3 muestras para realizar un perfil PK individualizado de los valores de FVIII. Los parámetros PK analizados son: t1/2, AUC, nivel pico (NP), nivel valle a las 24, 48 y/o 72 h (NV24/NV48/NV72) y tiempo para alcanzar niveles de FVIII del 5%, 2% y 1% (T5%/T2%/T1%). También analizamos los ratios de t1/2 y AUC, el nº dosis semanales y la dosis/kg/semana. Para comparar los parámetros PK entre ambos periodos empleamos los test de Wilcoxon y Kruskal-Wallis (SPSS®). Los resultados se expresaron con la mediana y el rango o rango intercuartílico (RIC). Resultados: Se han analizado 64 pacientes procedentes de 8 hospitales españoles (48 switch a Elocta® y 16 a Adynovi®), 62 con HA grave y 2 con HA moderada, con una mediana de edad de 32 años (rango=5-64) y sin diferencias en el peso entre ambos periodo [71, 0 (rango=12-116) vs 72, 0 (16, 9- 116) kg; p=0, 156]. La dosis/kg/semana se redujo tras el switch a EHL [74, 5 (RIC:59, 2-108, 1) vs 69, 2 (RIC:46, 2-96, 7) UI/kg/semana; p<0, 0001], así como ..

Incidencia de infección por hepatitis C en donantes de cabezas femorales para el banco de tejidos

The live donors of femoral heads belong to a highly specific group in terms of age and pathological characteristic, forming the core of the group who supply many tissue banks with spongy bone, to cover the needs of several specialities in the field of repair and corrective surgery. Analysis for the presence of the hepatitis C virus in this population was conducted as a part of quality control programs, while habitual blood donors from the same geographical location were used as the control group. Although the comparison of results could give rise to erroneous interpretations, due to the lack of qualitative fit between the groups, a much higher incidence of infection by VHC was found in the donors of spongy bone than was the case for blood donors (3.816% vs. 0.569%), although a smaller proportion of donors had hepatic alterations (measured by transaminases). In spite of the fact that the prevalence of VHC is almost 6 times that corresponding to the population as a whole, the elimination of live donors of spongy bone would create serious problems with supply to tissue banks. We therefore propose that more severe exclusion criteria be applied to the selection of bone donors, and also that sterilisation techniques be employed, using physical - chemical procedures (liophilisation, dehydration, chemical treatment, irradiation) to process these tissues. We also recommend that younger multiple organ tissue donors be used as sources of spongy bone for cold storage that is not to be subjected to any additional sterilisation treatment.Los donantes vivos de cabezas femorales constituyen un grupo de edad y características patológicas muy concreto, y forman el núcleo más importante que nutre de hueso esponjoso a muchos Bancos de Tejidos, para dar cobertura a las necesidades de diversas especialidades quirúrgicas reparadoras y correctoras. Dentro de los programas de control de calidad, se analizó la prevalencia de infección por virus de hepatitis C entre esta población, tomando como grupo de control poblacional a donantes de sangre habituales de la misma localización geográfica, y cuyos datos constaban en los registros del Centro de Transfusión de la Comunidad Valenciana, en donde está ubicado el propio Banco de Tejidos. Aunque la comparación de resultados puede dar origen de interpretaciones erróneas debido al desajuste cualitativo de los grupos, se encontró una incidencia mucho más elevada de infección por VHC entre los donantes de hueso esponjoso que entre los donantes de sangre (3,816% vs. 0,569%), aunque con una proporción menor de donantes con alteraciones enzimáticas hepáticas (por medición de transaminasas). A pesar de que la incidencia hallada de VHC fue casi 6 veces la de la población general, la decisión de prescindir de los donantes vivos de hueso esponjoso crearía serios problemas de abastecimiento a los Bancos de Tejidos. Por ello se propone extremar la aplicación de los criterios de exclusión en la selección de donantes de hueso, y la implantación de técnicas de esterilización por procedimientos físico-químicos (liofilización, deshidratación, tratamiento químico, irradiación) para procesar estos tejidos, al tiempo que emplear los donantes multiorgánicos de tejidos, de edad más joven, como fuente de hueso esponjoso destinado a criopreservación sin tratamiento de esterilización adicional

Emicizumab-induced photosensitivity

Emicizumab constitutes a novel and effective prophylaxis for hemophilia A patients with and without inhibitors. In this case report, we describe an emicizumab-induced photosensitivity that forced permanent sun-exposure suppression. To the best of our knowledge, this side effect had not been communicated until present

Hidden myelodysplastic syndrome (MDS): A prospective study to confirm or exclude MDS in patients with anemia of uncertain etiology

[Introduction]: Diagnosis of myelodysplastic syndromes (MDSs) when anemia is the only abnormality can be complicated. The aim of our study was to investigate the primary causes of anemia and/or macrocytosis of uncertain etiology. [Methods]: We conducted a multicenter, prospective study over 4 months in three hematology laboratories. In step 1, we used an automated informatics system to screen 137 453 hemograms for cases of anemia and/or macrocytosis (n = 2702). In step 2, we excluded all patients whose anemia appeared to be due to a known cause. This left 290 patients had anemia of uncertain etiology. In step 3, we conducted further investigations, including a peripheral blood smear, and analysis of iron, vitamin B12, folate, and thyroid hormone levels. [Results]: A differential diagnosis was obtained in 139 patients (48%). The primary causes of anemia were iron deficiency (n = 59) and megaloblastic anemia (n = 39). In total, 25 hematologic disorders were diagnosed, including 14 patients with MDS (56%). The median age of MDS patients was 80 years, 12 had anemia as an isolated cytopenia, and most (n = 10) had lower‐risk disease (IPSS‐R ≤ 3.5). SF3B1 mutations were most frequent (n = 6) and correlated with the presence of ring sideroblasts (100%) and associated with better prognosis (P = 0.001). [Conclusions]: Our prospective, four‐step approach is an efficient and logical strategy to facilitate the diagnosis of MDS on the basis of unexplained anemia and/or macrocytosis, and may allow the early diagnosis of the most serious causes of anemia. Molecular analysis of genes related to MDS could be a promising diagnostic and prognostic approach.This work was also partially financed by the Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III (ISCIII) (PI 17/01741 from MDC and PI 17/01966 from JMB)

The safety of activated eptacog beta in the management of bleeding episodes and perioperative haemostasis in adult and paediatric haemophilia patients with inhibitors.

INTRODUCTION: Haemophilia patients with inhibitors often require a bypassing agent (BPA) for bleeding episode management. Eptacog beta (EB) is a new FDA-approved recombinant activated human factor VII BPA for the treatment and control of bleeding in haemophilia A or B patients with inhibitors (≥12 years of age). We describe here the EB safety profile from the three prospective Phase 3 clinical trials performed to date. AIM: To assess EB safety, immunogenicity and thrombotic potential in children and adults who received EB for treatment of bleeding and perioperative care. METHODS: Using a randomized crossover design, 27 subjects in PERSEPT 1 (12-54 years) and 25 subjects in PERSEPT 2 (1-11 years) treated bleeding episodes with 75 or 225 μg/kg EB initially followed by 75 μg/kg dosing at predefined intervals as determined by clinical response. Twelve PERSEPT 3 subjects (2-56 years) received an initial preoperative infusion of 75 μg/kg (minor procedures) or 200 μg/kg EB (major surgeries) with subsequent 75 μg/kg doses administered intraoperatively and post-operatively as indicated. Descriptive statistics were used for data analyses. RESULTS: Sixty subjects who received 3388 EB doses in three trials were evaluated. EB was well tolerated, with no allergic, hypersensitivity, anaphylactic or thrombotic events reported and no neutralizing anti-EB antibodies detected. A death occurred during PERSEPT 3 and was determined to be unlikely related to EB treatment by the data monitoring committee. CONCLUSION: Results from all three Phase 3 trials establish an excellent safety profile of EB in haemophilia A or B patients with inhibitors for treatment of bleeding and perioperative use