ficolin-2 adsorption to polysulfone dialyzer initiates the lectin pathway of complement activation, mediates dialysis-induced leukopenia, and results in a significant depletion of ficolin-2, an essential component of innate immunity.
Thrombogenicity is one of the most important biocompatibility markers of artificial material. Anticoagulation is commonly used to reduce thrombogenicity of the extracorporeal circuit (ECC) during intermittent hemodialysis (IHD). In some situations, systemic anticoagulants are contraindicated. The aim of our study was to compare thrombogenicity parameters during IHD with three different methods without a systemic anticoagulation effect. In a prospective, randomized, and crossover study, we examined 10 stable patients during IHD with (i) regular saline flushes of ECC; (ii) regional citrate anticoagulation (RCA); and (iii) AN69 ST membrane after ECC priming according to the manufacturer's recommendations. Before IHD and after 10, 60, 120, and 240 min, we measured the platelet count and the plasma concentrations of platelet factor 4 (PF4) and thrombin/antithrombin complexes (TAT). All 10 procedures with RCA were successfully completed after 4 h, whereas 6/10 procedures with saline flushes and 5/10 procedures with AN69 ST were finished prematurely because of clotting (P < 0.05). The TAT production was significantly increased during saline flushes and AN69 ST compared with RCA (P< 0.05). Platelet activation demonstrated by rising PF4 was present during all three methods. Markers of coagulation cascade activation were progressively increasing during IHD with RCA, saline flushes, and AN69 ST. The activation was significantly lower during RCA, and according to thrombogenicity, RCA is the most effective among compared anticoagulation methods.
The purpose of this study was to determine whether or not regional citrate anticoagulation (RCA) controlled by ionized calcium (iCa(2+)) would overcome thrombogenicity, prevent hemostasis, and complement activation during hemodialysis (HD). RCA was performed in 10 patients during 10 HD sessions using a polysulfone membrane in an effort to keep iCa(2+) at dialyzer outlet at < or =0.4 mmol/L. Compared to baseline, plasma levels of thrombin-antithrombin III complexes rose significantly at 240 min, and tissue factor and complement C5a component levels at 30 and 240 min of the procedure. Thrombocyte count declined significantly at 30 and 240 min, while activated clotting time (ACT) did not increase significantly, and platelet factor 4 as well as von Willebrand factor levels did not alter significantly. While ACT correlated significantly with some thrombogenicity markers, iCa(2+) did not correlate with ACT, changes in hemostasis, or C5a. We conclude the usually recommended iCa(2+) levels in the HD extracorporeal circuit did not guarantee the complete overcoming of thrombogenicity, prevention of hemostasis, and complement activation.
Based on plasma TAT levels, ECC priming with an UFH-containing solution reduces the thrombogenicity of the AN69 ST membrane. There is no significant difference between both types of priming concerning PF4 and thrombocyte count.
Reportedly, citrate-based dialysis solution enables heparin dose tapering or even complete exclusion, particularly in postdilution hemodiafiltration (HDF). The aim of the study was to verify this strategy in predilution setting and to assess its short-term safety, efficacy, and biocompatibility. Ten regular hemodialysis patients were assigned to predilution HDF on acetate- and citrate-based dialysis solutions (0.8 mmol/l trisodium citrate) at random order. Acetate HDF was performed using routine dose of heparin while citrate HDF was heparin free. Plasma calcium, thrombin-antithrombin complexes (TAT), and citrate levels were measured at 0, 30, 60, 120, and 240 min. Following each session, a semiquantitative dialyzer clotting score (DCT 1-5) was assessed and HDF adequacy was determined as spKt/V. Statistical relevance was tested by ANOVA with pP < 0.05 held significant, data are given as means ± standard deviations. All sessions were accomplished successfully, premature termination or circuit re-setting was not necessary. However, DCT was significantly higher in citrate-HDF compared to acetate-HDF regimen (3.4 ± 0.65 and 1.8 ± 0.79, respectively, P = 0.002) as well as TAT generation rate (increase per session by factor 11.0 ± 8.43 and 2.1 ± 1.26, respectively, P = 0.004 between regimens). Ionized calcium declined only by the end of citrate-HDF (from 1.09 ± 0.086 to 0.99 ± 0.030 mmol/L, P = 0.002) yet without accompanying clinical symptoms. Systemic citrate levels increased along the citrate-HDF session but stayed an order of magnitude below concentrations needed to establish citrate anticoagulation (peak at 0.276 ± 0.112 mmol/L). Dialysis adequacy estimated by spKt/V was found lower in citrate-HDF vs. acetate-HDF (1.48 ± 0.163 and 1.58 ± 0.165, respectively, P = 0.006). Although predilution HDF using citrate-based dialysate is feasible without heparin, both dialysis adequacy and biocompatibility is significantly compromised. Therefore, this approach can be adopted for a single procedure but is not acceptable on a regular basis.
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