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Differences in Coagulation-Relevant Parameters: Comparing Cryoprecipitate and a Human Fibrinogen Concentrate

Sophia Stanford, Ashok Roy, Tom Cecil, Oliver Hegener, Petra Schulz, Anna Turaj, Sean Lim, Emily Arbuthnot


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.


Cryoprecipitate is a traditional source of fibrinogen for replacement therapy in the treatment of trauma bleeding cases, post-partum hemorrhage, and in a range of surgical settings [1]. Despite its capacity to replenish plasma fibrinogen levels in patients with coagulopathic bleeding [1], the variable fibrinogen content of cryoprecipitate makes accurate dosing challenging [2]. There are also safety concerns associated with cryoprecipitate, mainly that of pathogen transmission due to the lack of pasteurization/viral inactivation during preparation.

Materials and methods

NHSBT cryoprecipitate was analyzed at the Peritoneal Malignancy Institute at Basingstoke and North Hampshire Hospital, Hampshire Hospital NHS Foundation Trust, UK. HFC (Fibryga, Octapharma AG) was analyzed at Octapharma Plasma Research and Development, Vienna, Austria. The primary objective was to characterize NHSBT cryoprecipitate content and compare the variability of the coagulation profile with that of HFC.


The results per standard dose were largely similar to those shown for individual cryoprecipitate bags and HFC batches. Per standard cryoprecipitate dose (10 U), the mean fibrinogen (Clauss) level was approximately half that in a standard 4 g dose of HFC (2.14 vs. 3.95 g, respectively; p<0.001), whereas the mean FXIII level was higher in a standard cryoprecipitate dose compared with HFC (p<0.001; S2 Table).


Our findings demonstrate that, compared with cryoprecipitate, the tested HFC is a more reliable and consistent source for accurate dosing of fibrinogen and FXIII due to significantly higher and more standardized concentrations. The advantages of HFC over cryoprecipitate translate to accurate dosing, faster preparation/administration time, evidence of clinical efficacy, and improved safety. Furthermore, HFC can be stored in clinical areas at room temperature and does not require frozen storage, unlike cryoprecipitate. In addition to fibrinogen and FXIII, we show that cryoprecipitate also contains VWF, FVIII, fibronectin, alpha-2 antiplasmin, TAT, PMPs, prothrombin fragment 1+2, FPA, plasminogen, and D-dimer at variable levels.


Cryoprecipitate treatment does not appear to be a reliable choice for goal-directed therapy in bleeding management. Cryoprecipitate may also potentially elevate VWF and FVIII to prothrombotic levels. The varying levels of prothrombotic and anticoagulative elements in cryoprecipitate may impair treatment goals and have variable risks toward thrombosis or the continuation of bleeding in critical patients; high PMP activity may strongly contribute to this. In comparison, treatment with HFC enables a tailored and accurate fibrinogen replacement strategy, especially in the setting of managed care and responsible patient blood management concepts in both trauma and surgery.


Editorial assistance was provided by Ben McDermott (Portland Medical Communications Ltd), funded by Octapharma, in accordance with GPP3.

Citation: Stanford S, Roy A, Cecil T, Hegener O, Schulz P, Turaj A, et al. (2023) Differences in coagulation-relevant parameters: Comparing cryoprecipitate and a human fibrinogen concentrate. PLoS ONE 18(8): e0290571.

Editor: Alessio Branchini, University of Ferrara: Universita degli Studi di Ferrara, ITALY

Received: January 20, 2023; Accepted: August 9, 2023; Published: August 30, 2023

Copyright: © 2023 Stanford et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: 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:

Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: S.S., A.R., T.C., A.T., S.L., and E.A. declare no competing interests and have not received any remuneration from Octapharma for this study. O.H. and P.S. are employees of Octapharma AG. Funding for writing this article was provided by Octapharma AG. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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