A Practical, One-Clinic Visit Protocol for Pharmacokinetic Profile Generation with the ADVATE myPKFiT Dosing Tool in Severe Hemophilia A Subjects.

Standard pharmacokinetic (PK) assessments are demanding for persons with hemophilia A, requiring a 72-hour washout and 5 to 11 timed blood samples. A no-washout, single-clinic visit, sparse sampling population PK (PPK) protocol is an attractive alternative. Here, we compared PK parameters obtained with a traditional washout, 6-sampling time point PPK protocol with a no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol in persons with severe hemophilia A (SHA) receiving ADVATE. A total of 39 inhibitor-negative males with SHA (factor VIII activity [FVIII:C] < 2%) were enrolled in a prospective sequential design PK study. Participants completed a washout, 6-sampling time point PPK protocol as well as a no-washout, reverse 2-sampling time point protocol, with samples taken during a single 3-hour clinic visit 24 hours post home infusion of FVIII and then 3 hours post infusion in clinic. FVIII:C levels were analyzed by one-stage and chromogenic assays; blood group and von Willebrand factor antigen (VWF:Ag) were determined; and PK parameters were analyzed using the ADVATE myPKFiT dosing tool. There was moderate to almost perfect agreement for the PK parameters obtained with the 2- and the 6- point PPK protocols using a one-stage FVIII:C assay and a substantial to almost perfect agreement using a chromogenic FVIII:C assay. Significant associations between specific PK parameters and blood group and VWF:Ag were observed. The no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol can be used in the routine clinical setting since it demonstrates sufficient accuracy compared with the more demanding and less practical washout, 6-sampling time point PPK protocol in persons with SHA receiving ADVATE.

Measuring the impact of changing from standard half-life (SHL) to extended half-life (EHL) FVIII prophylaxis on health-related quality of life (HRQoL) in boys with moderate/severe haemophilia A: Lessons learned with the CHO-KLAT tool.

INTRODUCTION: In many countries, there is a shift from standard half-life (SHL) to extended half-life (EHL) clotting factor concentrates (CFCs). AIM: To describe the experience of switching from SHL to an EHL FVIII CFC and the impact of this on frequency of infusions, factor consumption, bleeding rates and HRQoL using the Canadian Hemophilia Kids' Life Assessment Tool (CHO-KLAT). METHODS: A retrospective chart review was conducted at a single haemophilia treatment centre in 2018 that included boys (ages: 4-18 years) with moderate/severe haemophilia A, without inhibitors, who switched from a SHL to an EHL FVIII CFC in the previous 2 years and for whom HRQoL data were available. RESULTS: The study cohort comprised 38 boys [mean (SD) age: 11.0 (3.4) years] with moderate (n = 5)/severe (n = 33) haemophilia A. The switch was associated with a 33% reduction in the number of weekly infusions from a median of 3.5 to 2.3 (P < .0001) and a 17% reduction in median FVIII consumption from 103 IU/kg/wk to 85.5 IU/kg/wk (P = .004). There was no significant change in annualized joint bleed rates or in CHO-KLAT scores. CONCLUSIONS: Despite documenting several benefits of switching to EHL FVIII (less infusions, lower factor consumption with no increase in bleeding), our study did not demonstrate any improvement in HRQoL. We conclude that either the current CHO-KLAT tool is not optimized to measure burden of treatment administration in boys with low bleed rates switching from SHL to EHL FVIII CFCs or that a reduction of 1.2 infusions/week does not result in a meaningful change in HRQoL.

Microbiological quality of hemodialysis water in a three-year multicenter study in Uruguay.

BACKGROUND: The microbiological quality of treated water is a very important issue in hemodialysis (HD) centers. Water treatment may have a dramatic effect on microbial contamination because of bacterial colonisation of the different parts of the system such as storage tanks, softeners or deionisers. Therefore, HD centers must have stringent quality programmes including regular water monitoring for microbiological analysis. We report the results of a three-year study (July 97 to June 2000) including bacteriological quality analysis of 3129 water samples from 32 out of 38 HD centers throughout Uruguay. METHODS: Bacteriological analysis of water samples was based on heterotrophic count, total coliform count and Pseudomonas aeruginosa presence/absence, according to the procedures proposed by the Association for the Advancement of Medical Instrumentation (AAMI). RESULTS: Heterotrophic counts of 83% of the samples were under 200 colony forming units (CFU) /mL (AAMI limit of compliance) and the water samples after the final bactericidal treatment showed 99% compliance. The points showing the worst results were softeners and deionisers (60% acceptance). CONCLUSIONS: In comparison with a similar study in Uruguay, from January 96 to June 97 at the same microbiological laboratory, there has been a marked improvement in the microbiological quality of water for hemodialysis.