PhD defence M.C.H.J. (Tine) Goedhart

Below is a brief summary about the dissertation:

Hemophilia A and B are inborn bleeding disorders characterized by a deficiency in coagulation factor VIII (FVIII) and factor IX (FIX), respectively. As a result, severely affected patients who exhibit <1IU/dL endogenous factor level and some moderate severe patients with factor levels between 1 and 5IU/dL, suffer from spontaneous bleeds, especially in large joints and muscles. Prophylaxis with factor or non-factor replacement therapy is the mainstay of treatment. Factor replacement therapy is administered intravenously administered factor concentrates several times a week and is traditionally prescribed based on body weight. However, a large inter-individual variation (IIV) in the pharmacokinetics (PK) of factor concentrates has been demonstrated, resulting in different factor levels in each individual after the infusion of the same amount of factor concentrate per kilogram body weight. To account for this IIV, PK-guided dosing has been introduced. With information from a population PK model, only a limited number of blood samples, e.g. two to five, are necessary to estimate individual PK parameters that can be used to construct personalized dosing regimens. In this thesis, we present a number of studies encompassing the highs and lows of the implementation of PK-guided prophylactic dosing of factor concentrates in hemophilia in daily, clinical practice. In the first part of the thesis, we focus on the enhancement of PK-guided dosing in clinical practice. In the second part, we focus on a PK-guided dosing in clinical practice, with views on value and validation.