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

Richard Fisher, Gary W Moore, Michael J Mitchell, Letian Dai, Siobhan Crichton, Nuttha Lumlertgul, Marlies Ostermann, Richard Fisher, Gary W Moore, Michael J Mitchell, Letian Dai, Siobhan Crichton, Nuttha Lumlertgul, Marlies Ostermann

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://ichgcp.net/clinical-trials-registry/NCT02486614.

Keywords: Acute kidney injury; CRRT; Citrate; Clotting; Continuous renal replacement therapy; Platelets; Thrombin.

Conflict of interest statement

MO has received speaker honoraria and research funding from Fresenius Medical and Baxter and is a member of an advisory board for NxStage and Pfizer. GWM reports consultancy fees from Technoclone and was employed at Guy's & St Thomas' Hospital at the time of the study. RF, MM, LD, SC and NL report no conflict of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Cohort selection flowchart. BMI body mass index, CRRT continuous renal replacement therapy, RCA regional citrate anticoagulation
Fig. 2
Fig. 2
Changes in systemic measurements of coagulation over duration of treatment. INR International Normalised Ratio, APTTr activated partial thromboplastin time ratio, TGA thrombin generation assay, PFSCA platelet function assay using collagen/adenosine diphosphate, PFSCE platelet function assay using collagen/epinephrine, CT closure time. Repeated measures ANOVAs compared systemic parameters from baseline to 48 h. Post hoc pairwise comparisons found significant differences between haemoglobin at baseline and 36 h (p = 0.030) and baseline and 48 h (p = 0.018); platelets at baseline and 36 h (p = 0.035) and baseline and 48 h (p = 0.040) and INR at baseline and 36 h (p = 0.034) and baseline and 48 h (p = 0.024). There were no significant differences in systemic parameters on CRRT
Fig. 3
Fig. 3
Changes in circuit measurements of coagulation over duration of treatment. INR International Normalised Ratio, APTTr activated partial thromboplastin time ratio, TGA thrombin generation assay, PFSCA platelet function assay using collagen/adenosine diphosphate, PFSCE platelet function assay using collagen/epinephrine, CT closure time. Repeated measures ANOVAs of measurements from the circuit compared data from 12 to 48 h. Only INR differed overtime, with a significant difference between 12 and 48 h in post hoc comparisons (p = 0.002)
Fig. 4
Fig. 4
Bland–Altman plots showing difference between systemic and circuit measurements. INR International Normalised Ratio, APTTr activated partial thromboplastin time ratio, TGA thrombin generation assay, PFSCA platelet function assay using collagen/adenosine diphosphate, PFSCE platelet function assay using collagen/epinephrine, CT closure time. Lines shown represent the mean differences in systemic and circuit measurements and 95% limits of agreement

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Source: PubMed

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