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

Article


Fisher, R., Moore, G., Mitchell, M., Dai, L., Crichton, S., Lumlertgul, N. and Ostermann, M. 2022. 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. Annals of Intensive Care. 12 (1), pp. 1-11. https://doi.org/10.1186/s13613-022-01004-w
TypeArticle
TitleEffects 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
AuthorsFisher, R., Moore, G., Mitchell, M., Dai, L., Crichton, S., Lumlertgul, N. and Ostermann, M.
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

KeywordsAcute kidney injury; Citrate; Clotting; CRRT; Continuous renal replacement therapy; Thrombin; Platelets
PublisherSpringer
JournalAnnals of Intensive Care
ISSN2110-5820
Electronic2110-5820
Publication dates
Online31 Mar 2022
PrintDec 2022
Publication process dates
Submitted05 Nov 2021
Accepted18 Mar 2022
Deposited01 Apr 2022
Output statusPublished
Publisher's version
License
File Access Level
Open
Copyright Statement

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Digital Object Identifier (DOI)https://doi.org/10.1186/s13613-022-01004-w
LanguageEnglish
Permalink -

https://repository.mdx.ac.uk/item/89vq0

Download files


Publisher's version
13613_2022_Article_1004.pdf
License: CC BY 4.0
File access level: Open

  • 121
    total views
  • 80
    total downloads
  • 2
    views this month
  • 0
    downloads this month

Export as

Related outputs

Diagnosing thrombophilia: the case for genetic or functional testing?
Favaloro, E.J., Moore, G.W. and Pasalic, L. 2025. Diagnosing thrombophilia: the case for genetic or functional testing? Expert Review of Molecular Diagnostics. 25 (12), pp. 841-846. https://doi.org/10.1080/14737159.2025.2588621
Survey on current practice in thrombophilia testing: from phenotype to genotype. Communication from the SSC of the ISTH
Van Laer, C., Moore, G.W., Majumder, R., Corral, J., Freson, K., Ignjatovic, V. and Orlando, C. 2025. Survey on current practice in thrombophilia testing: from phenotype to genotype. Communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis. https://doi.org/10.1016/j.jtha.2025.10.032
International Council for Standardization in Haematology (ICSH) recommendations for the performance and interpretation of activated partial thromboplastin time and prothrombin time mixing tests
Adcock, D.M., Moore, G., Kershaw, G.W., Montalvao, S. and Gosselin, R. 2024. International Council for Standardization in Haematology (ICSH) recommendations for the performance and interpretation of activated partial thromboplastin time and prothrombin time mixing tests. International Journal of Laboratory Hematology. 46 (5), pp. 777-788. https://doi.org/10.1111/ijlh.14344
International Council for Standardization in Haematology field study evaluating optimal interpretation methods for activated partial thromboplastin time and prothrombin time mixing studies
Gosselin, R.C., Moore, G.W., Kershaw, G.W., Montalvão, S. and Adcock, D.M. 2023. International Council for Standardization in Haematology field study evaluating optimal interpretation methods for activated partial thromboplastin time and prothrombin time mixing studies. Archives of Pathology & Laboratory Medicine. 148 (8), pp. 880-889. https://doi.org/10.5858/arpa.2023-0030-oa
Analytical dilemmas in lupus anticoagulant detection
Moore, G. 2023. Analytical dilemmas in lupus anticoagulant detection. Exploration of Immunology. 3, pp. 300-324. https://doi.org/10.37349/ei.2023.00104
ADAMTS13 activity measurement by ELISA and fluorescence resonance energy transfer assay
Moore, G., Llusa, M., Griffiths, M. and Binder, N. 2023. ADAMTS13 activity measurement by ELISA and fluorescence resonance energy transfer assay. in: Favaloro, E. and Gosselin, R. (ed.) Hemostasis and Thrombosis: Methods and Protocols New York, NY Humana.
ADAMTS13 activity: Screening test protocol
Moore, G., Griffiths, M. and Binder, N. 2023. ADAMTS13 activity: Screening test protocol. in: Favaloro, E. and Gosselin, R. (ed.) Hemostasis and Thrombosis: Methods and Protocols New York, NY Humana.
Lupus anticoagulant testing: Dilute prothrombin time (dPT)
Moore, G. 2023. Lupus anticoagulant testing: Dilute prothrombin time (dPT). in: Favaloro, E. and Gosselin, R. (ed.) Hemostasis and Thrombosis: Methods and Protocols New York, NY Humana.
Lupus anticoagulant testing: Taipan snake venom time with ecarin time as confirmatory test
Moore, G. 2023. Lupus anticoagulant testing: Taipan snake venom time with ecarin time as confirmatory test. in: Favaloro, E. and Gosselin, R. (ed.) Hemostasis and Thrombosis: Methods and Protocols New York, NY Humana.
ADAMTS13 antibody and inhibitor assays
Moore, G., Vetr, H. and Binder, N. 2023. ADAMTS13 antibody and inhibitor assays. in: Favaloro, E. and Gosselin, R. (ed.) Hemostasis and Thrombosis: Methods and Protocols New York, NY Humana.
Activated partial thromboplastin time and prothrombin time mixing studies: current state of the art
Adcock, D., Moore, G., Montalvão, S., Kershaw, G. and Gosselin, R. 2022. Activated partial thromboplastin time and prothrombin time mixing studies: current state of the art. Seminars in Thrombosis and Hemostasis. 49 (6), pp. 571-579. https://doi.org/10.1055/s-0042-1756196
Added value of antiphosphatidylserine/prothrombin antibodies in the workup of thrombotic antiphospholipid syndrome: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies
Vandevelde, A., Chayoua, W., de Laat, B., Moore, G., Musiał, J., Zuily, S., Wahl, D. and Devreese, K. 2022. Added value of antiphosphatidylserine/prothrombin antibodies in the workup of thrombotic antiphospholipid syndrome: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies. Journal of Thrombosis and Haemostasis. 20 (9), pp. 2136-2150. https://doi.org/10.1111/jth.15785
Direct oral anticoagulants‐Remove versus Taipan snake venom time for detection of a lupus anticoagulant in patients taking oral direct factor Xa inhibitors
White, D., Moore, G., Besser, M., MacDonald, S. and Thomas, W. 2022. Direct oral anticoagulants‐Remove versus Taipan snake venom time for detection of a lupus anticoagulant in patients taking oral direct factor Xa inhibitors. Research and Practice in Thrombosis and Haemostasis. 6 (1), pp. 1-8. https://doi.org/10.1002/rth2.12648
Semiquantitative interpretation of anticardiolipin and antiβ2glycoprotein I antibodies measured with various analytical platforms: communication from the ISTH SSC subcommittee on Lupus Anticoagulant/Antiphospholipid antibodies
Vandevelde, A., Chayoua, W., de Laat, B., Gris, J., Moore, G., Musiał, J., Zuily, S., Wahl, D. and Devreese, K. 2022. Semiquantitative interpretation of anticardiolipin and antiβ2glycoprotein I antibodies measured with various analytical platforms: communication from the ISTH SSC subcommittee on Lupus Anticoagulant/Antiphospholipid antibodies. Journal of Thrombosis and Haemostasis. 20 (2), pp. 508-524. https://doi.org/10.1111/jth.15585
Snake venoms in diagnostic hemostasis and thrombosis
Moore, G. 2022. Snake venoms in diagnostic hemostasis and thrombosis. Seminars in Thrombosis and Hemostasis. 48 (02), pp. 145-160. https://doi.org/10.1055/s-0041-1732465
International multicenter, multiplatform study to validate Taipan snake venom time as a lupus anticoagulant screening test with ecarin time as the confirmatory test: communication from the ISTH SSC subcommittee on Lupus Anticoagulant/Antiphospholipid antibodies
Moore, G., Jones, P., Platton, S., Hussain, N., White, D., Thomas, W., Rigano, J., Pouplard, C., Gray, E. and Devreese, K. 2021. International multicenter, multiplatform study to validate Taipan snake venom time as a lupus anticoagulant screening test with ecarin time as the confirmatory test: communication from the ISTH SSC subcommittee on Lupus Anticoagulant/Antiphospholipid antibodies. Journal of Thrombosis and Haemostasis. 19 (12), pp. 3177-3192. https://doi.org/10.1111/jth.15438
Applying index of circulating anticoagulant to mixing tests with lupus anticoagulant screen and confirm reagents can distinguish with high specificity between lupus anticoagulants and direct factor Xa inhibitors
Kumano, O., Amiral, J., Dunois, C., Peyrafitte, M. and Moore, G. 2021. Applying index of circulating anticoagulant to mixing tests with lupus anticoagulant screen and confirm reagents can distinguish with high specificity between lupus anticoagulants and direct factor Xa inhibitors. International Journal of Laboratory Hematology. 43 (4), pp. 771-778. https://doi.org/10.1111/ijlh.13571
Clinical validation of an automated fluorogenic factor XIII activity assay based on isopeptidase activity
Leitner, M., Büchold, C., Pasternack, R., Binder, N. and Moore, G. 2021. Clinical validation of an automated fluorogenic factor XIII activity assay based on isopeptidase activity. International Journal of Molecular Sciences. 22 (3). https://doi.org/10.3390/ijms22031002