OBJECTIVES: In a separate document, we have provided specific guidance on performing individual pharmacokinetic (PK) studies using limited samples in persons with hemophilia with the goal to optimize prophylaxis with clotting factor concentrates. This paper, intended for clinicians, aims to describe how to interpret and apply PK properties obtained in persons with hemophilia. METHODS: The members of the Working Party on population PK (PopPK) of the ISTH SSC Subcommittee on Factor VIII and IX and rare bleeding disorders, together with additional hemophilia and PK experts, completed a survey and ranking exercise whereby key areas of interest in the field were identified. The group had regular web conferences to refine the manuscript's scope and structure, taking into account comments from the external feedback to the earlier document. RESULTS: Many clinical decisions in hemophilia are based on some form of explicit or implicit PK assessment. Individual patient PK profiles can be analyzed through traditional or PopPK methods, with the latter providing the advantage of fewer samples needing to be collected on any prophylaxis regimen, and without the need the for a washout period. The most useful presentation of PK results for clinical decision making are a curve of the factor activity level over time, the time to achieve a certain activity level, or related parameters like half-life or exposure (AUC). Software platforms have been developed to deliver this information to clinicians at the point of care. Key characteristics of studies measuring average PK parameters were reviewed, outlining what makes a credible head-to-head comparison among different concentrates. Large data collections of PK and treatment outcomes currently ongoing will advance care in the future. CONCLUSIONS: Traditionally used to compare different concentrates, PK can support tailoring of hemophilia treatment by individual profiling, which is greatly simplified by adopting a PopPK/Bayesian method and limited sampling protocol.

Arthur Bloom Haemophilia Centre School of Medicine University Hospital of Wales Cardiff University Cardiff UK

Boston Hemophilia Center Boston Children's Hospital Boston MA USA

Department of Health Research Methods Evidence and Impact McMaster University Hamilton ON Canada

Department of Infection Immunity and Cardiovascular Disease University of Sheffield Sheffield UK

Department of Internal Medicine University Hospital Center Zagreb Croatia

Department of Medicine McMaster University Hamilton ON Canada

Department of Paediatric Haematology University Hospital Brno Brno Czech Republic

Department of Pathology and Molecular Medicine Queen's University Kingston ON Canada

Department of Pediatric Hematology Erasmus University Medical Center Sophia Children's Hospital Rotterdam The Netherlands

Division of Hematology Oncology Hospital for Sick Children and Department of Pediatrics University of Toronto Toronto ON Canada

Grifols Durham NC USA

Hospital Pharmacy Clinical Pharmacology Academic Medical Centre Amsterdam The Netherlands

Italian Association Haemophilia Centers Milan Italy

Pfizer Collegeville PA USA

School of Pharmacy University of Waterloo Waterloo ON Canada

Sobi Stockholm Sweden

St Jude Children's Research Hospital Memphis TN USA

The Royal London Hospital Haemophilia Centre Barts and The London School of Medicine and Dentistry London UK

University of Toronto Toronto ON Canada

Van Creveldkliniek University Medical Center Utrecht University Utrecht The Netherlands

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First experience of a hemophilia monitoring platform: florio HAEMO