High variability in Factor IX one-stage assay in samples spiked with nonacog beta pegol among different pairs of reagent/detection system.

INTRODUCTION: Haemophilia B (HB) is an X-linked hereditary bleeding disorder characterized by coagulation factor IX (FIX) deficiency. To improve the quality of life of patients and adherence to treatment, recombinant factor concentrates modified to extend their half-life have been developed, called extended half-life factors (EHL: extended half-life). Nonacog beta pegol (N9-GP) is a glycopegylated recombinant human FIX molecule that has a half-life of 93 h with a single dose and has shown a higher recovery percentage than other molecules. To diagnose and monitor the treatment of haemophiliac patients, FIX activity is determined with the one-stage clotting assay (OSA) and/or the chromogenic assay. The objective of this work, carried out in three centres, was to measure the recovery of N9-PG with 10 different activated partial thromboplastin time (APTT) reagents on three platforms, in samples spiked in vitro with N9-GP, at four different concentration levels. METHODS: It was measured the recovery of N9-GP with 10 different APTT reagents (polyphenol, ellagic acid, silice dioxide, colloidal silica as APTT activator on three platforms, in sample spiked in vitro with N9-GP. RESULTS: The results show heterogeneity in the activity of N9-GP measured by OSA with the different APTT reagents when the calibrations were performed with the specific calibrator of each coagulometer. A recovery percentage between 87% and 108% was obtained only with polyphenol and ellagic acid as activator in the three platforms evaluated. The other reagents studied overestimate or underestimate, with no clear profile. When a calibration curve was performed with a calibrator prepared from the N9-GP vial, all APTT reagents met the established recovery requirement. CONCLUSION: APTT reagents with polyphenol or ellagic acid as activator would be the only ones appropriate when using the commercially available OSA with specific calibrator to monitor patients treated with N9-GP.

Pacientes pediátricos en insuficiencia hepática y pasibles de trasplante: Correlación del tiempo de protrombina y Razón Internacional Normatizada (RIN) entre dos combinaciones de reactivos e instrumentos de medición / Pediatric patients with liver failure who are candidates for transplantation: correlation of prothrombin time and international normalized ratio (INR) in two combinations of reagents and measurement instruments

El objetivo de este trabajo es correlacionar el tiempo de protrombina y RIN en dos combinaciones de reactivos e instrumentos de medición en muestras de pacientes pediátricos con insuficiencia hepática asistidos en el Hospital de Pediatría Juan P. Garrahan y pasibles de trasplante. Se estudiaron 62 muestras de sangre obtenidas de pacientes, con presencia de patología hepática, definida con evidencia bioquímica de injuria hepática. Se utilizaron 2 (dos) analizadores, un coagulómetro BCT de detección foto-óptica y un Sta Compact de detección electromagnética. Para el analizador BCT se utilizó el reactivo Thromborel S, en el Sta Compact el Sta Neoplastine. Se trabajó con el ISI correspondiente a cada Reactivo /Instrumento. El análisis estadístico se realizó con el programa informático Stata 9.0, aplicando los tests estadísticos de coeficiente de correlación (rho) y el intervalo de confianza 95%; se determino la ecuación de la recta, para cada caso, se determino la equivalencia clínica a través del EP evaluator. Nuestra conclusión es que en los pacientes con insuficiencia hepática, se halló mejor correlación estadística y clínica para el TP%, debido a que se independiza del Tiempo (seg.) y de la calidad de la tromboplastina (diferentes concentraciones de factor tisular). Según nuestros resultados el sistema ISI/RIN, no seria válido para aplicarlo a pacientes con falla hepática y pasible de trasplante. Una de las causas es la falta de un reactivo de Tromboplastina calibrado con plasmas de pacientes con insuficiencia hepática, ya que para el cálculo del ISI, se usan plasmas de pacientes con terapia ACO (AU)

The objective of this study was to correlate prothrombin time (PT) and INR in two combinations of reagents and measurement instruments samples of pediatric patients with liver failure seen at the Hospital de Pediatría Juan P. Garrahan and who are candidates for liver transplantation. Sixtytwo blood samples were studied obtained from patients with liver pathology defined by biochemical evidence of liver injury. Two analyzers were used: a BCT coagulometer with photo-optical clot detection and a Sta Compact with an electromagnetic detection system. For the BCT analyzer Thromborel S was used and in the Sta Compact Sta Neoplastine was used. The ISI corresponding to each Reagent /Instrument was used. Statistical analysis was done with Stata 9.0, with correlation coefficient (rho) and a 95% confidence interval; for each case the equation of the straight line was determined. Clinical equivalence was determined through the EP evaluator. Our conclusion is that in patients with liver failure a better statistical and clinical correlation was found for PT%, as it is independent of Time (sec.) and of thromboplastin quality (different concentrations of tissue factor). According to our results, the ISI/INR system is not adequate in patients with liver failure who are candidates for liver transplantation. One of the reasons is that we lack a thromboplastin reagent that is calibrated against plasma of patients with liver failure, as for the ISI calculation plasma of patients with OAC therapy is used (AU)