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.

Osmolyte channel regulation by ionic strength in skate RBC.

The aim of this study was to determine whether the opening of the osmolyte channel in skate red blood cells (RBC) is regulated by intracellular electrolyte concentration and conductivity. Consistent with previous studies, experiments with hyperosmotic preincubation before cell swelling or swelling with an isosmotic electrolyte (e.g., ammonium chloride) showed that an increase in ionic strength inhibits the opening of the taurine channel. However, a decrease in intracellular ionic strength did not always stimulate taurine efflux to the same degree. Whereas hyposmotic swelling caused a large increase in taurine efflux, swelling induced by treatment with isosmotic nonelectrolytes produced much smaller stimulation. Results with assays for band 3 phosphorylating enzymes were consistent with those from the taurine efflux studies; stimulation of enzyme activity was lower in cells that were swollen with isosmotic nonelectrolyte media than in cells swollen in hyposmotic media. These results indicate that a decrease in ionic strength is not the only signal for the opening of the taurine channel in skate RBC. Ionic strength does affect channel activity, but there must also be some other regulator.