Effects of regional citrate anticoagulation on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving continuous renal replacement therapy for acute kidney injury: a prospective study

Abstract

Background Regional citrate anticoagulation (RCA) is recommended for continuous renal replacement therapy (CRRT). However, filter life varies and premature filter clotting can occur. The aims of this explorative prospective study were to investigate the effects of RCA on thrombin generation, fibrinolysis and platelet function in critically ill patients receiving CRRT, to compare clotting parameters between systemic and intra-circuit blood samples, and to screen participants for coagulation disorders. We recruited critically ill adult patients admitted to a 30-bedded Intensive care unit in a tertiary care hospital who required CRRT with RCA for acute kidney injury (AKI). Patients with pre-existing thrombotic, bleeding tendencies or a CRRT duration less than 48 h were excluded. We measured coagulation and thrombophilia parameters at baseline. Thrombin generation, D-dimer and platelet function were measured pre-CRRT and at 12, 24, 36, 48 and 72 h after commencing CRRT using blood samples taken from the arterial line and the circuit. Results At baseline, all eleven patients (mean age 62.4 years, 82% male) had Factor VIII and von Willebrand Factor concentrations above reference range and significantly increased peak thrombin generation. During CRRT, there were no significant changes in systemic maximum peak thrombin generation, time to peak thrombin generation, fibrinogen, D-dimer and platelet function analysis. We observed no significant difference between paired samples taken from the patient's arterial line and the circuit. Conclusions Critically ill patients with AKI requiring CRRT are hypercoagulable. Citrate used for anticoagulation during CRRT does not affect thrombin generation, D-dimer or platelet function. Systemic clotting parameters reflect intra-circuit results. Trial registration: ClinicalTrials.gov Identifier: NCT02486614. Registered 01 July 2015—Registered after recruitment of first patient. https://clinicaltrials.gov/ct2/show/NCT02486614

Extracorporeal Blood Purification with the Oxiris Membrane in Septic Shock

“…This important pro-inflammatory reaction, as expected, activates the coagulation response: platelets are in the lower normal range, PAI-1 is increased, and TEG analysis showed high or normal MA in more of 50% of patients, confirming that hypercogulation is a common trait during sepsis [14].…”

“…Finally, histones and other dams or pumps are strongly adsorbed by heparin layers, which may be early saturated and then inhibited to anticoagulate the membrane [18]. Thus, citrate protocol we used in this study seems a rational alternative to heparin [14].…”

Immunomodulation Effect of Regional Citrate Anticoagulation in Acute Kidney Injury Requiring Renal Replacement Therapy

“…They showed significant decreased levels of MPO and IL-8 in the RCA group compared to the heparin group. Fisher et al [26] explored other coagulation parameters on fibrinogen, D-dimer, thrombin generation assay, and platelet function assay. Results showed that RCA did not affect thrombin generation, D-dimer function, or platelet function.…”

Analysis of the extracorporeal anticoagulation effect of modified citrate infusion during continuous renal replacement therapy in critically ill patients

“…The major complications of citrate anticoagulation include citrate accumulation, hypocalcaemia, hypernatraemia, and metabolic acid–base disorders [26]. Citrate affects systemic coagulation, and there have been few reports of bleeding induced by citrate anticoagulation [27]. The ideal state of anticoagulation in CRRT is to achieve a good anticoagulation effect without associated complications.…”