The effect of regional citrate anti-coagulation on the coagulation system in critically ill patients receiving continuous renal replacement therapy for acute kidney injury - an observational cohort study

Abstract

BackgroundRegional anticoagulation with citrate is the recommended first line treatment for patients receiving continuous renal replacement therapy (CRRT). There is wide variability in filter patency which may be due to differences in patient characteristics and local practice. It is also possible that citrate has effects on primary and secondary haemostasis, fibrinolysis and platelet function that are still unknown. The primary aim of the study is to describe the effect of citrate on coagulation and fibrinolysis pathways in both the patient and the haemodialysis circuit.MethodsThe study will recruit 12 adult patients admitted to the intensive care unit, requiring CRRT with regional citrate anticoagulation for acute kidney injury. Patients with pre-existing thrombotic or bleeding tendencies will be excluded. Thrombin generation, clot lysis and platelet function will be measured at baseline and at 12, 24, 36, 48 and 72 h after commencing CRRT (from the patient and from the circuit). We will describe the evolution of parameters over time as well as the differences in parameters between the patient and the circuit.DiscussionThe study will provide new data on the effects of citrate during continuous renal replacement therapy which is not currently available. We will minimise confounding factors through the use of tight exclusion criteria and accept that this will slow down recruitment. Depending on the results, we hope to incorporate the findings into existing clinical guidelines and clinical practice with the aim to prevent premature filter clotting and interruptions in treatment.Trial registrationThe study was registered with clinicaltrials.gov on 10th June 2015 (NCT02486614).

Perioperative Doppler measurements of renal perfusion are associated with acute kidney injury in patients undergoing cardiac surgery

“…We found that reduced systemic perfusion pressure was associated with development of AKI, confirming previous studies 25 , 26 . Further, a recent study of patients in the ICU found that abnormalities in renal and portal venous Doppler measurements were associated with major adverse kidney events 15 .…”

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

“…Also, we used widely available assays that could have been applied in this context if our results had suggested that monitoring citrate anticoagulation with them could be valuable. Lastly, the study took 2.5 years to complete and not all planned investigations were performed in all patients [ 17 ]. This reflects our very tight inclusion criteria and the challenges of studying coagulation biochemistry in critically ill patients.…”

“…Prior to commencing CRRT, blood was sampled from the patient's arterial line for measurement of full blood count (FBC) and clotting profile, including prothrombin time expressed as international normalised ratio (INR), activated partial thromboplastin time (APTT) expressed as activated partial thromboplastin time ratio (APTTr), Clauss fibrinogen, D-dimer and platelet function assay (PFA-100). Baseline assessment for hereditary and acquired coagulopathies was performed as previously described [ 17 ]. Plasma samples were stored at − 80 °C for subsequent batch testing of thrombin generation.…”

“…It has also been suggested that systemic haemostasis results do not always reflect coagulation parameters within the circuit and may lead to inappropriate clinical decision-making [ 14 ]. Whether citrate also impacts thrombin generation, fibrinolysis or platelet function and impacts filter life through these mechanisms is unknown [ 15 – 17 ]. Until recently, there were no data to this effect.…”