{'fraction_non_alphanumeric': 0.035035035035035036, 'fraction_numerical': 0.01001001001001001, 'mean_word_length': 5.475161987041036, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Citrate Anticoagulation for Extracorporeal Circuits: Effects on Whole Blood Coagulation Activation and Clot Formation

Dear Sir, Adequate anticoagulation is a precondition for any effective hemodialysis therapy to prevent clotting in the extracorporeal circuit. While systemic anticoagulation with unfractionated heparin has been widely used, it is associated with several disadvantages , such as an increase in bleeding risk. Hemodialysis of patients who are at high risk for hemorrhages is complicated by a 10–30% incidence of bleeding [1, 2]. Alternatives to conventional heparin anticoagulation that are designed to reduce bleeding complications include limited-dose heparinization, low-molecular-weight heparins, neutraliza-tion of heparin with protamine, prostacyclin infusion or saline-flush dialysis. Although the incidence of bleeding complications can be reduced, each of these methods has its own limitations [3, 4]. The use of regional citrate anticoagula-tion for hemodialysis and continuous renal replacement therapies in patients at high risk for bleeding offers unique advantages over other anticoagulation alternatives [3–6]. By virtue of chelating ionized calcium, citrate is a powerful anticoagulant. Free calcium ions are required for activation of coagulation (fig. 1) but are also reported to have concentration dependent effects on clot polymeri-zation [7–9]. Citrate anticoagulation is usually monitored by the determination of activated clotting time (ACT). However, this method is affected by factor deficiencies and other an-ticoagulants. Measuring ionized calcium by ion-selective calcium electrodes may be an inexpensive alternative way for monitoring citrate effects in regional citrate anticoagula-tion. The aim of this study was to assess the dose-response relationship of citrate anticoa-gulation on coagulation activation and clot formation in whole blood. In addition, the value of direct determination of ionized calcium by ion-selective calcium electrodes for monitoring of citrate anticoagulation was evaluated. Venous blood was taken from 6 healthy volunteers after informed consent and blood samples we immediately analyzed. Coagula-tion studies were performed with tubes containing anticoagulant citrate dextrose-A (ACD-A) in different amounts (0–5.65 mmol citrate/l of whole blood). ACD-A is an isotonic mixture of dextrose, citrate acid, and trisodium citrate (38 mmol/l anhydrous citric acid, 75 mmol/l trisodium citrate) as commonly used by blood banks for blood sampling and cell storage. Whole blood ACT was analyzed with a KC4-coagulometer (Sigma-Amelung, Lem-go, Germany) using kaolin as surface activa-tor (100 ng of kaolin added to 0.3 ml of whole blood). This test serves as a model for contact activation (intrinsic pathway) and determines the time until an initial formation of fibrin fibers is detected. Further, we performed thromboelastography (TEG) with a RoTEG analyser (Nobis, Endingen, Ger-many) [10]. With this test, fibrin formation …