title: A systematic review of prothrombin complex concentrate dosing strategies to reverse vitamin K antagonist therapy.
abstract: Management of patients with a major bleed while on vitamin K antagonist (VKA) is a common clinical challenge. Prothrombin Complex Concentrates (PCC) provide a rapid reversal of VKA induced coagulopathy. However, a well-defined PCC dosing strategy, especially in emergency setting, is still lacking. We performed a systematic review to describe the currently used PCC dosing strategies and to present their efficacy in terms of target INR achievement and clinical outcome. We used outcome definitions as used in the individual studies. MEDLINE and EMBASE databases were searched for studies reporting the use of PCC for emergency VKA reversal. Twenty-eight studies, including 4 randomized trials, were found. In these, fifteen different PCC dosing protocols were identified in which the PCC dose ranged from 8 to 50IU factor IX/kg. These strategies were based on: bodyweight; bodyweight and initial INR; bodyweight and initial INR and target INR; individual doctors decision; or a fixed dose. Study quality was moderate with large variation in outcome definitions. Relatively good clinical and INR outcomes were reported with the use of any treatment protocol while less good results were reported for INR outcome when a predefined protocol was missing (doctor strategy). Lowest PCC dosages were infused in the fixed dose strategy. In emergency VKA reversal, a predefined PCC dosing protocol seems essential. We found no evidence that one dosing strategy is superior. Future studies should be designed to investigate if body weight and INR are relevant for PCC dosing. In these, we need uniform outcome definitions.
authors.affiliation: Division of Haemostasis and Thrombosis, Department of Haematology, University of Groningen, University Medical Centre Groningen, The Netherlands; Central Hospital Pharmacy, The Hague, The Netherlands. Electronic address: n.khorsand@ahz.nl.
authors.forename: Nakisa
authors.initials: N
authors.lastname: Khorsand
authors.affiliation: Division of Haemostasis and Thrombosis, Department of Haematology, University of Groningen, University Medical Centre Groningen, The Netherlands.
authors.forename: Hilde A M
authors.initials: HA
authors.lastname: Kooistra
authors.affiliation: Department of Clinical Pharmacy, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Reinier M
authors.initials: RM
authors.lastname: van Hest
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Nic J G M
authors.initials: NJ
authors.lastname: Veeger
authors.affiliation: Division of Haemostasis and Thrombosis, Department of Haematology, University of Groningen, University Medical Centre Groningen, The Netherlands.
authors.forename: Karina
authors.initials: K
authors.lastname: Meijer
mesh_terms: D001779:Blood Coagulation Factors / Q000008:administration & dosage*; D001835:Body Weight; D004334:Drug Administration Schedule; D006801:Humans; D019934:International Normalized Ratio; D011516:Prothrombin / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D001779:Blood Coagulation Factors; D014812:Vitamin K; C025667:prothrombin complex concentrates; D011516:Prothrombin
keywords: Hematology (hemostasis and thrombosis); Vitamin-K dependent coagulation proteins; oral anticoagulants; prothrombin complex concentrates