Differences in coagulation-relevant parameters: comparing cryoprecipitate and a human fibrinogen concentrate
Differences in coagulation-relevant parameters: comparing cryoprecipitate and a human fibrinogen concentrate
Background: variable fibrinogen content within cryoprecipitate makes accurate dosing challenging in patients with coagulopathic bleeding, in addition to pathogen transmission risks associated with its administration. Purified and standardized human fibrinogen concentrates (HFCs) represent reliable alternatives. Full cryoprecipitate characterization is required to inform selection of an appropriate fibrinogen source for supplementation therapy.
Methods: extended biochemical comparison of pooled cryoprecipitate and HFC (Fibryga, Octapharma) was performed using commercially available assays to determine levels of variability in cryoprecipitate and HFC. In addition to standard procoagulant factors, measurements included activities of platelet-derived microparticles (PMPs) and plasminogen, and levels of fibrin degradation products.
Results: cryoprecipitate contains lower fibrinogen levels than HFC (4.83 vs.19.73 g/L; p<0.001), translating to approximately half the amount of fibrinogen per standard cryoprecipitate dose (two pools, pre-pooled from five donations each) vs. HFC (2.14 vs. 3.95 g; p<0.001). Factor XIII (FXIII) levels were also lower in cryoprecipitate vs. HFC (192.17 vs. 328.33 IU/dL; p = 0.002). Levels of procoagulants in cryoprecipitate, such as von Willebrand Factor (VWF) and factor VIII (FVIII), were highly variable, as was PMP activity. A standard cryoprecipitate dose contains significantly higher levels of measured plasminogen and D-dimer fragments than a standard HFC dose.
Conclusion: the tested HFC is a more reliable fibrinogen and FXIII source for accurate dosing compared with cryoprecipitate. Cryoprecipitate appears considerably less predictable for bleeding management due to wide variation in pro- and anticoagulation factors, the presence of PMPs, and the potential to elevate VWF and FVIII to prothrombotic levels.
Stanford, Sophia
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Roy, Ashok
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Cecil, Tom
fff8d82e-2019-402f-a931-1c9591ffc133
Hegener, Oliver
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Schulz, Petra
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Turaj, Anna
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Lim, Sean
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Arbuthnot, Emily
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Stanford, Sophia
ea11cec4-d952-4e42-b44c-70e02eb3ec66
Roy, Ashok
33951307-0af0-4042-932a-173d544964a7
Cecil, Tom
fff8d82e-2019-402f-a931-1c9591ffc133
Hegener, Oliver
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Schulz, Petra
6736c280-914c-4430-832f-416e486a8879
Turaj, Anna
fbbc48ea-28cf-4db7-ae4a-c16ce7b3857a
Lim, Sean
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Arbuthnot, Emily
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Stanford, Sophia, Roy, Ashok, Cecil, Tom, Hegener, Oliver, Schulz, Petra, Turaj, Anna, Lim, Sean and Arbuthnot, Emily
(2023)
Differences in coagulation-relevant parameters: comparing cryoprecipitate and a human fibrinogen concentrate.
PLoS ONE, 18 (8), [e0290571].
(doi:10.1371/journal.pone.0290571).
Abstract
Background: variable fibrinogen content within cryoprecipitate makes accurate dosing challenging in patients with coagulopathic bleeding, in addition to pathogen transmission risks associated with its administration. Purified and standardized human fibrinogen concentrates (HFCs) represent reliable alternatives. Full cryoprecipitate characterization is required to inform selection of an appropriate fibrinogen source for supplementation therapy.
Methods: extended biochemical comparison of pooled cryoprecipitate and HFC (Fibryga, Octapharma) was performed using commercially available assays to determine levels of variability in cryoprecipitate and HFC. In addition to standard procoagulant factors, measurements included activities of platelet-derived microparticles (PMPs) and plasminogen, and levels of fibrin degradation products.
Results: cryoprecipitate contains lower fibrinogen levels than HFC (4.83 vs.19.73 g/L; p<0.001), translating to approximately half the amount of fibrinogen per standard cryoprecipitate dose (two pools, pre-pooled from five donations each) vs. HFC (2.14 vs. 3.95 g; p<0.001). Factor XIII (FXIII) levels were also lower in cryoprecipitate vs. HFC (192.17 vs. 328.33 IU/dL; p = 0.002). Levels of procoagulants in cryoprecipitate, such as von Willebrand Factor (VWF) and factor VIII (FVIII), were highly variable, as was PMP activity. A standard cryoprecipitate dose contains significantly higher levels of measured plasminogen and D-dimer fragments than a standard HFC dose.
Conclusion: the tested HFC is a more reliable fibrinogen and FXIII source for accurate dosing compared with cryoprecipitate. Cryoprecipitate appears considerably less predictable for bleeding management due to wide variation in pro- and anticoagulation factors, the presence of PMPs, and the potential to elevate VWF and FVIII to prothrombotic levels.
Text
journal.pone.0290571
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Submitted date: 25 February 2022
Accepted/In Press date: 9 August 2023
e-pub ahead of print date: 30 August 2023
Additional Information:
Funding Information:
Editorial assistance was provided by Ben McDermott (Portland Medical Communications Ltd), funded by Octapharma, in accordance with GPP3. This study was sponsored and funded by Octapharma AG. The sponsor provided financial support for the study and for writing the manuscript. The sponsor was involved in study design, analysis and interpretation of the data, in the writing of the report, and in the decision to submit the article for publication. S.S., A.R., T.C., A. T., S.L., and E.A. have not received any remuneration from Octapharma for this study. O.H. and P.S. are employees of Octapharma AG. The funder URL is: https://cas5-0-urlprotect. trendmicro.com:443/wis/clicktime/v1/query?url= https%3a%2f%2fwww.octapharma.ch%2fde% 2f&umid=61ccbdb6-df2f-4fcb-b2bfc3bc6a60bbe1&auth= e956d4e801a29d4b16f358f6efec87033cf96c3c- 35ba41ed90f988198c02f46aef7a03eb5662450e.
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Local EPrints ID: 455527
URI: http://eprints.soton.ac.uk/id/eprint/455527
ISSN: 1932-6203
PURE UUID: 110a39fc-f4bb-4a50-8e14-48730e2c828d
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Date deposited: 24 Mar 2022 17:35
Last modified: 16 Mar 2024 16:14
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Contributors
Author:
Sophia Stanford
Author:
Ashok Roy
Author:
Tom Cecil
Author:
Oliver Hegener
Author:
Petra Schulz
Author:
Anna Turaj
Author:
Emily Arbuthnot
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