Emergency reversal of pentasaccharide anticoagulants: a systematic review of the literature

Objectives: To conduct a systematic review of the literature to answer the question: Has administration of recombinant activated factor VII (rFVIIa) or prothombin complex concentrate (PCC) or activated PCC (aPCC) been demonstrated to be effective in reversing pendasaccharide anticoagulants (PSAs)? Background: Fondaparinux and idraparinux are ultra-short, synthetic PSAs. Typical anticoagulation reversal with either vitamin K and fresh frozen plasma or protamine sulphate does not reverse PSAs. Mechanistically, it is plausible that rFVIIa, PCC and aPCC may be effective reversal agents for PSAs. However, the available data are limited. Materials/Methods: We conducted a systematic review of MEDLINE, EMBASE, CINAHL and the Cochrane Library without date or language limitations designed to answer the question: Has administration of rFVIIa, PCC or aPCC been demonstrated to be effective in reversing PSAs? The quality of the included studies was assessed based on standard methodologies. Relevant information was synthesised and reported. Results: After an initial literature search, 197 abstracts were identified, of which 14 articles were reviewed in their entirety. Ultimately, five studies were identified that met inclusion and exclusion criteria. Although the literature is limited, the best available data support the use of rFVIIa for serious bleeding in patients anticoagulated with PSAs. Conclusions: Limited data support the use of rFVIIa as a reversal agent for serious bleeding in patients who are anticoagulated with PSAs. The optimal dose, role for concomitant use of platelets or antifibrinolytic agents and exact indications for reversal remain to be determined. Such investigations are urgently needed as use of PSAs increases.