One piece of the puzzle: Population pharmacokinetics of FVIII during perioperative Haemate P®/Humate P® treatment in von Willebrand disease patients

Introduction: Many patients with von Willebrand disease (VWD) are treated on demand with von Willebrand factor and factor VIII (FVIII) containing concentrates present with VWF and/or FVIII plasma levels outside set target levels. This carries a risk for bleeding and potentially for thrombosis. Development of a population pharmacokinetic (PK) model based on FVIII levels is a first step to more accurate on-demand perioperative dosing of this concentrate

Seed dormancy and seedling emergence studies in Avena fatua L.

Studies were made of seedling emergence of three phenotypes of Avena fatua L. with different coloured lemmas (fA, fB, fC) originally collected from one site. Each phenotype was grown under the same conditions in 1975 and the resulting seed buried 25 mm deep in soil immediately after collection. The soil was either left uncultivated (all phenotypes) or cultivated monthly (phenotype fA only). Seedling emergence was assessed weekly and the number of remaining viable seeds was determined at the end of three years. Seeds of different lines of A. fatua (fA phenotypes) obtained from separate locations were grown under the same conditions in 1983, buried and seedling emergence monitored for 8.5 months. Without cultivation, overall emergence (mean of three phenotypes) in successive autumns and springs was 9 %, 18 %, 9 %, 33 %, < 1 %, 14 % and < 1 %. A further 3 % of viable seeds were recovered at the end of the experiment. Periodicity of emergence was the same for all phenotypes. Actual numbers of seedlings emerging in each of the periods varied between phenotypes. Total emergence of seed from the inner zone of panicles was significantly less than that from the outer zone, although there was little difference between the two zones in each of the natural emergence periods. Cultivation increased emergence, particularly from secondary seed in the first spring after burial, but did not changes its periodicity. By the second spring seed numbers had declined, and seedling counts were similar from cultivated and non-cultivated soil. No viable seed remained in the cultivated soil after three years. Emergence from the two lines of fA was very different. Seedling emergence occurred after hot dry conditions, or in warm periods immediately after periods of chilling, particularly those below 4-degrees-C

Emergence of Chenopodium album and Stellaria media under different climatic conditions

Experiments with the germination of two weed species from different origins under different climatic conditions has led to modelling their germination and emergence

Emergence of Chenopodium album and Stellaria media under different climatic conditions

Experiments with the germination of two weed species from different origins under different climatic conditions has led to modelling their germination and emergence

An adapted thermal-gradient block for the germination of photoblastic seeds

This work describes an adapted thermal-gradient block with internal illumination, allowing experiments with light-requiring seeds. The temperature dependence study on the germination of the photoblastic Plantago tomentosa seeds was carried out in order to test the performance of the apparatus. With the aid of the model described here, some parameters related to the response of the seeds to temperature could be estimated, showing that the apparatus was suitable for the studies on the temperature dependence of photoblastic seeds.<br>Este trabalho descreve um bloco termo-gradiente com iluminação interna, adaptado para estudos com sementes que requerem luz para germinar. Para se aferir o desempenho do equipamento, este foi usado num experimento sobre o efeito da temperatura na germinação de sementes fotoblásticas de Plantago tomentosa. Com o protótipo aqui descrito, alguns parâmetros da resposta dessa semente à temperatura puderam ser estimados, mostrando que o equipamento pode ser usado em estudos sobre a dependência térmica da germinação de sementes fotoblásticas

One piece of the puzzle: Population pharmacokinetics of FVIII during perioperative Haemate P (R)/Humate P (R) treatment in von Willebrand disease patients

Introduction: Many patients with von Willebrand disease (VWD) are treated on demand with von Willebrand factor and factor VIII (FVIII) containing concentrates present with VWF and/or FVIII plasma levels outside set target levels. This carries a risk for bleeding and potentially for thrombosis. Development of a population pharmacokinetic (PK) model based on FVIII levels is a first step to more accurate on-demand perioperative dosing of this concentrate. Methods: Patients with VWD undergoing surgery in Academic Haemophilia Treatment Centers in the Netherlands between 2000 and 2018 treated with a FVIII/VWF plasma-derived concentrate (Haemate (R) P/Humate P (R)) were included in this study. Population PK modeling was based on measured FVIII levels using nonlinear mixed-effects modeling (NONMEM). Results: The population PK model was developed using 684 plasma FVIII measurements of 97 VWD patients undergoing 141 surgeries. Subsequently, the model was externally validated and reestimated with independent clinical data from 20 additional patients undergoing 31 surgeries and 208 plasma measurements of FVIII. The observed PK profiles were best described using a one-compartment model. Typical values for volume of distribution and clearance were 3.28 L/70 kg and 0.037 L/h/70 kg. Increased VWF activity, decreased physical status according to American Society of Anesthesiologists (ASA) classification (ASA class >2), and increased duration of surgery were associated with decreased FVIII clearance. Conclusion: This population PK model derived from real world data adequately describes FVIII levels following perioperative administration of the FVIII/VWF plasma-derived concentrate (Haemate (R) P/Humate P (R)) and will help to facilitate future dosing in VWD patients.Thrombosis and Hemostasi