Factor VIII activity of BAY 94-9027 is accurately measured with most commonly used assays: Results from an international laboratory study.

INTRODUCTION: Discrepancies in the measurement of modified factor VIII (FVIII) products have been recognized, highlighting the need for adjustments in clinical laboratory practices to ensure effective monitoring of patients treated with these products, particularly using the one-stage (activated partial thromboplastin time [aPTT]) assay. AIM: To assess the ability of clinical laboratories to measure the activity of BAY 94-9027, a PEGylated extended half-life FVIII product, using routine (predominantly one-stage) assays in clinical laboratories METHODS: Blinded samples of FVIII-deficient plasma spiked with defined levels of BAY 94-9027 and a recombinant FVIII product comparator were provided to 52 clinical laboratories that routinely conduct FVIII testing. Samples were provided at 3 concentrations (low, medium and high), and laboratories analysed the samples using routine in-house one-stage and, when available, chromogenic assays. Acceptable spiked recovery (accuracy) of the local laboratory methods to measure BAY 94-9027 was the primary endpoint of the study. RESULTS: Accurate FVIII measurements were obtained at all concentrations for both products using the chromogenic assay and most of the commonly used one-stage reagents, both ellagic acid and silica based. Two specific silica-based reagents, APTT-SP and PTT-A, underestimated BAY 94-9027 levels at all concentrations, consistent with previous findings. CONCLUSIONS: FVIII activity of BAY 94-9027 was accurately measured with most commonly used one-stage assays used in routine clinical practice. The chromogenic assay was also accurate. It is recommended that clinical laboratories identify and avoid specific inappropriate reagents, such as the APTT-SP and PTT-A, in their one-stage assays for FVIII monitoring.

Repeated anaesthesia with isoflurane and xylazine/levomethadone/fenpipramide premedication in female Beagle dogs: influence on general health and wellbeing.

Beagle dogs continue to be used in experimental studies and preclinical and clinical trials, many of which address the usage of anaesthesia. In order to reduce the number of animals, researchers tend to conduct several experiments on a single animal. The question arises, however, as to whether or not this frequent usage involves more than simply additional stress and discomfort for the individual animal. Within the framework of an existing study involving six female Beagle dogs, we investigated the effects of repeated (5) isoflurane anaesthesia with xylazine/levomethadone/fenpipramide premedication carried out at short intervals (2 weeks) and compared these with the effects of two treatments intermitted by a longer resting period (8 weeks). To verify our hypothesis that frequent anaesthesia affects the dog's wellbeing more than the occasional anaesthesia, the following parameters were measured at regular intervals: body weight, body temperature, respiratory rate, blood pressure, reflexes and heart rate, both at rest and during a treadmill exercise. In addition, recovery behaviour subsequent to anaesthesia was monitored for one hour. Our observations indicate that the anaesthetic effects are most prominent 24 h after the anaesthetic treatment. However, crossover analysis of our data cannot show that there is no statistical difference of whether dogs were anaesthetized occasionally or frequently. In our study, it appears that frequent anaesthesia within a two-week period did not affect the wellbeing and general health of Beagle dogs in a super-additive manner and that a minimum of two-week testing-free period is sufficient to ensure complete recovery from the unwanted effects induced by anaesthesia.