Sven Björkman

Bio: Sven Björkman is an academic researcher from Uppsala University. The author has contributed to research in topics: Haemophilia & Population. The author has an hindex of 29, co-authored 52 publications receiving 3273 citations. Previous affiliations of Sven Björkman include Malmö University & Lund University.

Consensus perspectives on prophylactic therapy for haemophilia: summary statement.

Abstract: Participants in an international conference on prophylactic therapy for severe haemophilia developed a consensus summary of the findings and conclusions of the conference. In the consensus, participants agreed upon revised definitions for primary and secondary prophylaxis and also made recommendations concerning the need for an international system of pharmacovigilance. Considerations on starting prophylaxis, monitoring outcomes, and individualizing treatment regimens were discussed. Several research questions were identified as needing further investigation, including when to start and when to stop prophylaxis, optimal dosing and dose interval, and methods for assessment of long-term treatment effects. Such studies should include carefully defined cohorts, validated orthopaedic and quality-of-life assessment instruments, and cost-benefit analyses.

Prediction of drug disposition in infants and children by means of physiologically based pharmacokinetic (PBPK) modelling: theophylline and midazolam as model drugs

Abstract: Aims To create a general physiologically based pharmacokinetic (PBPK) model for drug disposition in infants and children, covering the age range from birth to adulthood, and to evaluate it with theophylline and midazolam as model drugs.

Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia

Abstract: The pharmacokinetic (PK) response to factor VIII (FVIII) and factor IX varies between patients and this has important clinical implications for treatment. Although PK is affected by patient characteristics, this relationship is too weak to infer a result for an individual and, if required, PK must be measured. An important determinant of the efficacy of prophylaxis is the length of time an individual spends with a low level of coagulation factor. This time is more dependent on the patient's coagulation factor half-life and the frequency of dosing than in vivo recovery and dose infused. Improved understanding of the effect of PK and dose frequency on factor levels in patients on prophylaxis will help tailor regimens to individuals better and allow more cost effective use of coagulation factor concentrates. Calculations suggest that adults need less FVIII per kg body weight than children. The effect of half-life on trough levels questions the logic of Monday, Wednesday, Friday dosing and suggests a role for innovative regimens including low-dose daily treatment which leads to either higher trough levels or decreased FVIII requirement. This may expand access to prophylaxis in healthcare systems with limited resources and potentially improve patient outcomes. The ideal trough level will vary between individuals and at different times of their lives and may be <1 IU dL(-1). If PK is to be used in routine clinical practice, a simplified method for its measurement is required and this methodology is becoming available.

Guidelines for the management of hemophilia.

Abstract: Hemophilia is a rare disorder that is complex to diagnose and to manage. These evidence-based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion-transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies.

Mechanism-Based Concepts of Size and Maturity in Pharmacokinetics

Abstract: Growth and development can be investigated using readily observable demographic factors such as weight and age. Size is the primary covariate and can be referenced to a 70-kg person with allometry using a coefficient of 0.75 for clearance and 1 for volume. The use of these coefficients is supported by fractal geometric concepts and observations from diverse areas in biology. Fat free mass (FFM) might be expected to do better than total body weight when there are wide variations in fat affecting body composition. Clearance pathways develop in the fetus before birth. The use of postnatal age as a descriptor of maturation is unsatisfactory because birth may occur prematurely; therefore postmenstrual age is a superior predictor of elimination function. A sigmoid E(max) model (Hill equation) describes gradual maturation of clearance in early life leading to a mature adult clearance achieved at a later age.

Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant.

Abstract: The indications for transfusing fresh-frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited. When transfused they can have unpredictable adverse effects. The risks of transmitting infection are similar to those of other blood components unless a pathogen-reduced plasma (PRP) is used. Of particular concern are allergic reactions and anaphylaxis, transfusion-related acute lung injury, and haemolysis from transfused antibodies to blood group antigens, especially A and B. FFP is not indicated in disseminated intravascular coagulation without bleeding, is only recommended as a plasma exchange medium for thrombotic thrombocytopenic purpura (for which cryosupernatant is a possible alternative), should never be used to reverse warfarin anticoagulation in the absence of severe bleeding, and has only a very limited place in prophylaxis prior to liver biopsy. When used for surgical or traumatic bleeding, FFP and cryoprecipitate doses should be guided by coagulation studies, which may include near-patient testing. FFP is not indicated to reverse vitamin K deficiency for neonates or patients in intensive care units. PRP may be used as an alternative to FFP. In the UK, PRP from countries with a low bovine spongiform encephalopathy incidence is recommended by the Departments of Health for children born after 1 January 1996. Arrangements for limited supplies of single donor PRP of non-UK origin are expected to be completed in 2004. Batched pooled commercially prepared PRP from donors in the USA (Octaplas) is licensed and available in the UK. FFP must be thawed using a technique that avoids risk of bacterial contamination. Plastic packs containing any of these plasma products are brittle in the frozen state and must be handled with care.

WFH Guidelines for the Management of Hemophilia, 3rd edition

Abstract: Alok Srivastava 1 | Elena Santagostino 2 | Alison Dougall 3 | Steve Kitchen 4 | Megan Sutherland 5 | Steven W. Pipe 6 | Manuel Carcao 7 | Johnny Mahlangu 8 | Margaret V. Ragni 9 | Jerzy Windyga 10 | Adolfo Llinás 11 | Nicholas J. Goddard 12 | Richa Mohan 13 | Pradeep M. Poonnoose 14 | Brian M. Feldman 15 | Sandra Zelman Lewis 16 | H. Marijke van den Berg 17 | Glenn F. Pierce 18 | on behalf of the WFH Guidelines for the Management of Hemophilia panelists and co-authors*

Physiologically-based pharmacokinetics in drug development and regulatory science.

Abstract: The application of physiologically-based pharmacokinetic (PBPK) modeling is coming of age in drug development and regulation, reflecting significant advances over the past 10 years in the predictability of key pharmacokinetic (PK) parameters from human in vitro data and in the availability of dedicated software platforms and associated databases. Specific advances and contemporary challenges with respect to predicting the processes of drug clearance, distribution, and absorption are reviewed, together with the ability to anticipate the quantitative extent of PK-based drug-drug interactions and the impact of age, genetics, disease, and formulation. The value of this capability in selecting and designing appropriate clinical studies, its implications for resource-sparing techniques, and a more holistic view of the application of PK across the preclinical/clinical divide are considered. Finally, some attention is given to the positioning of PBPK within the drug development and approval paradigm and its future application in truly personalized medicine.