Citrate Anticoagulation and Divalent Cations in Hemodialysis

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Abstract
Anticoagulation with citrate in combination with a calcium-free, magnesium-containing dialysate (Ca-Mg+) and intravenous supplementation of calcium is a safe procedure in renal failure patients at high risk of bleeding. Since magnesium may antagonize the anticoagulant effect of citrate by forming complexes with citrate, we studied the in vitro and in vivo interactions of calcium and magnesium on citrate anticoagulation. In the in vitro studies the activated partial thromboplastin time (APTT) was 88 s, both after addition of 3.0 µmol magnesium and after addition of 1.0 µmol calcium. The combination of 2.4 µmol magnesium and 1.0 µmol calcium achieved similar APTT values of about 35 s as 3.5 µmol calcium alone. Moreover, in a Lee-White blood clotting time, the anticoagulant effect of 7 µmol citrate was neutralized by either 10.5 µmol of a mixture of the two cations or 10.5 µmol calcium chloride alone. In 6 chronic hemodialysis patients the in vivo interactions of calcium and magnesium on citrate were measured. At the dialyzer outlet, the whole blood activated clotting time (ACT) was significantly (p -Mg+ dialysate than during dialysis with a calcium- and magnesium-free dialysate (Ca-Mg-). With the Ca-Mg- dialysate the ACT at the dialyzer outlet was still significantly longer than the ACT in the arterial line before citrate infusion. We also compared the serum concentrations of calcium and magnesium during the Ca-Mg- dialysate which was used in combination with intravenous calcium and magnesium supplementation – 0.18 and 0.08 mmol/min respectively – and during a conventional calcium- and magnesium-containing dialysate (Ca+Mg+). Serum total calcium concentrations were significantly higher during and after the Ca+Mg+ dialysate than with the Ca-Mg- dialysate. Plasma-ionized calcium concentrations were similar for the two dialysates at all times. However, the differences between post- and predialysis (post- minus predialysis) ionized calcium and serum magnesium with the Ca+Mg+ dialysate were significantly (p -Mg- dialysate. Thus, citrate achieves a more pronounced anticoagulation of the extracorporeal system with a Ca-Mg- dialysate than with a Ca-Mg+ dialysate. However, the calcium and magnesium supplementation rates – 0.18 and 0.08 mmol/min respectively -result in a short-term decrease of these divalent cations which may have repercussions for the parathyroid gland function.

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