Abstract
BackgroundRegional citrate anticoagulation has been associated with enhanced biocompatibility in hemodialysis, but the optimal dose of citrate remains to be established. Here, we compared parameters related to cellular activation during in vitro dialysis, using two doses of citrate.MethodsHuman whole blood, anticoagulated with either 3 mM or 4 mM of citrate, was recirculated in an in vitro miniaturized dialysis setup. Complement (C3a-desArg), soluble platelet factor 4 (PF4), thromboxane B2 (TXB2), myeloperoxidase (MPO), as well as platelet- and red blood cell-derived extracellular vesicles (EV) were quantified during recirculation. Dialyzer fibers were examined by scanning electron microscopy after recirculation to assess the activation of clotting and the deposition of blood cells.ResultsIncreases in markers of platelet and leukocyte activation, PF4, TXB2, and MPO were comparable between both citrate groups. Complement activation tended to be lower at higher citrate concentration, but the difference between the two citrate groups did not reach significance. A strong increase in EVs, particularly platelet-derived EVs, was observed during in vitro dialysis for both citrate groups, which was significantly less pronounced in the high citrate group at the end of the experiment. Assessment of dialyzer clotting scores after analysis of individual fibers by scanning electron microscopy revealed significantly lower scores in the high citrate group.ConclusionsOur data indicate that an increase in the citrate concentration from 3 mM to 4 mM further dampens cellular activation, thereby improving biocompatibility. A concentration of 4 mM citrate might therefore be optimal for use in clinical practice.
Highlights
Regional citrate anticoagulation (RCA) has found wide-spread application in centrifugal apheresis and has become the preferred method of anticoagulation for continuous renal replacement therapy (CRRT) due to its safety and effectiveness [1]
Increases in markers of platelet and leukocyte activation, platelet factor 4 (PF4), thromboxane B2 (TXB2), and MPO were comparable between both citrate groups
Complement activation tended to be lower at higher citrate concentration, but the difference between the two citrate groups did not reach significance
Summary
Regional citrate anticoagulation (RCA) has found wide-spread application in centrifugal apheresis and has become the preferred method of anticoagulation for continuous renal replacement therapy (CRRT) due to its safety and effectiveness [1]. RCA has been proposed to provide optimal anticoagulation for chronic hemodialysis patients with increased bleeding risk [2] and represents one of the two methods recommended by the current guidelines in this situation [3]. There is evidence that many of the inhibitory effects of citrate in the extracorporeal circuit are dose-dependent [12], and clinical data suggest that higher doses of citrate are required to improve blood compatibility [6, 7, 13]. A number of protocols for RCA have been proposed which differ with respect to the citrate dose in addition to other technical details, yet the optimal dosing of citrate in clinical practice remains to be established.
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