Fixed dosing of Prothrombin Complex Concentrate:Unpersonalizing Medicine

In this thesis the use of a fixed dose of four-factor prothrombin complex concentrate (4F-PCC) in bleeding emergencies on Vitamin K antagonists (VKA) is explored. Millions of patients worldwide remain best managed with vitamin K antagonist anticoagulants to prevent blood clots. If these patients have a major bleed, then the anticoagulant effect is recommended to be reversed with four-factor prothrombin complex concentrate (4F-PCC). The VKA associated major bleeding risk of 1-3 events per 100 patient-years annually translated for the Netherlands alone in 3700 major bleeding events and 518 deaths in 2019. Proper use of 4F-PCC as a reversal agent in VKA-related bleeds is therefore warranted, however the optimal dosing strategy is unknown.Traditionally, a variable dosing strategy—which uses patient-specific characteristics, such as body weight and international normalized ratio (INR), to achieve a certain target INR—is used as recommended by the manufacturer. In this way, a dose is calculated to achieve a specific target INR. More recent studies investigate a fixed, often lower, dose of 4F-PCC. Fixed dosing is increasingly being used in clinical practice, aiming to be simpler, faster and cheaper while preserving hemostatic effectiveness. There are still several knowledge gaps to overcome before fixed dosing of 4F-PCC could be fully supported. In this thesis we add to this research