title: Reversing the new oral anticoagulants with prothrombin complex concentrates (PCCs): what is the evidence?
abstract: Newer oral anticoagulants offer several advantages over traditional agents (e.g. warfarin), but they are still associated with a bleeding risk and currently there is no validated reversal treatment for them. While there is little support for the use of fresh frozen plasma, and limited data available on the effects of activated recombinant factor VII, preclinical data suggest that prothrombin complex concentrates (PCCs) may have potential in this setting. PCCs are currently used to successfully reverse warfarin-induced anticoagulation; however, clinical evidence for their use with new oral anticoagulants is lacking, with most of the available data coming from preclinical animal studies. Furthermore, there appears to be variation in the ability of different PCCs to reverse the coagulopathy induced by the new anticoagulants, and a lack of correlation between the reversal of laboratory test results and the reversal of anticoagulant-induced bleeding. Although there have been encouraging results, care must be taken in generalising findings from animal models and nonbleeding human subjects to the situation in bleeding patients. Ultimately, more evidence supporting anticoagulation reversal for new anticoagulants is needed, particularly regarding the treatment of bleeding in human patients in a clinical setting. According to the current evidence, use of PCCs may be considered a reasonable approach in dire clinical situations; however, a consensus has not yet been reached regarding PCC use or dosing, due to lack of clinical data.
authors.affiliation: Prof. Dr. Gerhard Dickneite, Preclinical R&D, CSL Behring, PO Box 1230, 35002 Marburg, Germany, Tel.: +49 6421 39 2306, Fax: +49 6421 39 4663, E-mail: Gerhard.Dickneite@cslbehring.com.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dickneite
authors.forename: Maureane
authors.initials: M
authors.lastname: Hoffman
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D003029:Coagulants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D003029:Coagulants; C025667:prothrombin complex concentrates
keywords: FXa inhibitors; Prothrombin complex concentrate; anticoagulant reversal; direct thrombin inhibitors; new oral anticoagulants