Fixed dosing of Prothrombin Complex Concentrate

After over forty years of using four-factor prothrombin complex concentrate, the optimal dose to use in bleeding emergencies in users on vitamin K antagonists is still not known. 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. Traditionally, a variable dosing strategy for 4F-PCC —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. We have therefore studied the use of a fixed dose 4F-PCC in VKA-related bleeds, looking primarily into its hemostatic effectiveness, as compared to the variable dose. In a large multicenter study, we found that a fixed dose of 1000 IU 4F-PCC produced good hemostatic effectiveness. Combined with the reduced door-to-needle time, ease of administration, and a comparable effect on INR to the variable dose, this suggests that fixed dosing is a viable alternative to variable dosing.

Dissertation: http://hdl.handle.net/11370/5d44e37c-803d-4c8d-9801-f9280f74748d