February 2019

Fibrinogen Replacement – What is the Latest News?

Authors: Wendy Owens, ART B Comm, Program Manager and Allison Collins MD FR CPC, Physician Clinical Project Coordinator, Ontario Regional Blood Coordinating Network

Fibrinogen is used in the management of trauma, surgical and obstetrical patients to help treat massive bleeding. Sources of fibrinogen available from Canadian Blood Services (CBS) include frozen plasma, cryoprecipitate, and fibrinogen concentrate. Until recently, there has been controversy over which was the best source of fibrinogen to use to treat massively bleeding patients. Is one better than the other?

Plasma is generally used in the management of massively bleeding patients but less for its fibrinogen content than as a source of the whole spectrum of coagulation components. Both cryoprecipitate and fibrinogen concentrate provide a larger dose of fibrinogen per volume.

Few studies have been done to directly compare the efficacy of cryoprecipitate versus fibrinogen concentrate so there has been a relatively slow uptake of fibrinogen concentrate across Canada and in particular, in Ontario which uses about 80% of all cryoprecipitate that CBS produces (in comparison, Ontario uses approximately 50% of what CBS produces for other blood components).

CBS targets the production and procurement of all blood components and products to address hospital needs. This can be challenging over holiday periods, when blood donations may be lower than in regular periods. In order to ensure that a sufficient number of platelets would be available over the December 2018 holiday season, a decision was made to divert production from cryoprecipitate in favour of platelets. (1) Unfortunately, demand for cryoprecipitate in Ontario turned out to be much higher than normal during this time and cryoprecipitate stocks ran low.

Both the National and Ontario Emergency Blood Management Committees were convened when CBS predicted that the inventory of cryoprecipitate would not meet hospital needs. A Green Advisory Phase was declared, and discussions began on contingencies for how this situation could be managed, particularly in Ontario where the demand was so high.

Transfusion experts on the Ontario Emergency Blood Management Committee suggested that the largest users of cryoprecipitate (most of the large teaching hospitals in the province) could make the switch over to using fibrinogen concentrate during the low inventory period, thus freeing up cryoprecipitate for any hospitals that did not yet have policies and procedures in place to stock and use fibrinogen concentrate. Many, but not all, of these large user hospitals had introduced fibrinogen concentrate for use in cardiac surgery, where there was a clinical trial underway (FIBrinogen REplacement in Surgery or FIBRES study). (2)

As a result of these actions by Ontario hospitals as well as those in other provinces, CBS was able to meet hospital demand for cryoprecipitate during this low inventory period and ensure patients’ needs were met, not only in Ontario but across Canada.

The National Advisory Committee on Blood and Blood Products recently released a revised statement on Fibrinogen Concentrate. (3) The July 2018 statement provides recommendations on the use and dosing of fibrinogen and states that fibrinogen concentrate, plasma and cryoprecipitate should be considered interchangeable. Decisions made on which of these products to use should be dependent on the clinical situation as well as the availability of the product.

Questions:
What should you do if your hospital has not yet introduced processes to accept and use fibrinogen concentrate?

Hospitals that have not yet developed a policy and procedures to stock, issue and infuse fibrinogen concentrate are being encouraged to do so to ensure they would have access to a source of fibrinogen replacement in the event that future shortages of cryoprecipitate occur.

How should you go about introducing this product in your hospital?

ORBCoN has recently revised and updated their ‘Introducing a New Blood Component or Product to Your Hospital Toolkit’. (4) In this document are steps to walk you through the process of introducing a new product into your inventory – from developing clinical guidelines, determining stock levels, seeking clinical committee approval and developing guidelines for nursing for product administration. Checklists are provided to further help support introduction of the product. An example of a Blood Component or Product Administration Guidelines/Monograph is provided using fibrinogen concentrate as the example product.

How do you decide if your hospital should consider stocking fibrinogen concentrate?

If you currently stock cryoprecipitate, you should consider having the ability to use fibrinogen concentrate as an alternative source of fibrinogen replacement, even if your preferred method of fibrinogen replacement is cryoprecipitate. There may be some inventory management advantages to stocking fibrinogen concentrate if you are a smaller site that only stocks cryoprecipitate and rarely uses it. Fibrinogen concentrate generally has a longer shelf life than cryoprecipitate and is much easier to redistribute to avoid wastage due to expiry.

If you are looking for additional support, you can contact your Regional Project Coordinator with ORBCoN and they can help connect you with hospitals which have already implemented this product and could potentially share their experience and/or policy and procedures.

References:

1. Canadian Blood Services. 2018 Holiday Message and Inventory Update – Customer Letter #2018-48. ; 2018.
2. Keyvan Karkouti, Jeannie Callum, Vivek Rao et al. Protocol for a phase III, non-inferiority, randomised comparison of a new fibrinogen concentrate versus cryoprecipitate for treating acquired hypofibrinogenemia, in bleeding cardiac surgical patients: the FIBRES trial. BMJ Open. 2018 April.
3. National Advisory Committee on Blood and Blood Products. nacblood.ca. [Online].; 2018 [cited 2019 January 15. Available from: http://www.nacblood.ca/resources/guidelines/fibrinogen.html.
4. Ontario Regional Blood Coordinating Network. transfusionontario.org. [Online].; 2018 [cited 2019 January 15. Available from: https://transfusionontario.org/documents/?cat=new-product.

On the Road to a Massive Hemorrhage Protocol (MHP): Updated February 2019

Author: Stephanie Cope, Administrative Project Coordinator, CE ORBCoN

In the June 2018 edition of this newsletter, we reported results of a baseline survey (n=150 Ontario hospitals) that looked at determining the proportion of hospitals with a formal, implemented Massive Hemorrhage Protocol (MHP) and the components it included – we were essentially ‘building’ our case for a Provincial MHP. We concluded from the survey that one third of Ontario hospitals did not have a formal MHP and those who did, had marked variability in all aspects of the protocols regardless of hospital size, specialties and/or services available onsite.

Using the survey results as well as published evidence, a multi-disciplinary panel of experts within Ontario (through Delphi-exercise to reach consensus) drafted recommendation statements for inclusion in a provincial MHP toolkit. The draft recommendations were circulated for external stakeholder review to all Ontario Transfusion Medicine Laboratories (for further dissemination throughout respective institutions) as well as circulated to the Trauma Association of Canada. The external review period closed December 17, 2018. We thank all those that took the time to review and provide feedback!

Once careful review of the feedback is complete, and the recommendations finalized, the expert panel will be broken up into subgroups to begin work on the provincial MHP toolkit. The multipart provincial MHP toolkit will include policies, procedures, checklists, forms, training material, simulation exercises and quality metrics. While implementing a single protocol for the province is preferred and would ensure compliance and standardized care to all patients, it is recognized that there is not a one-size-fits-all solution given the diversity of hospitals. As such, guidance for select patient populations as well as for smaller and /or remote hospitals remains a top priority in the creation of the toolkit. In addition to the materials in the toolkit, the rationale for each recommendation as well as supporting references will be provided and will aid in the implementation of the recommendations.

To assist in the quality improvement and tracking of the recommended quality metrics, the team will be investigating the option of an on-line data entry portal for outcome reporting which hospitals could utilize to review data for quality assurance purposes or produce reports for regulatory purposes.

Have you been busy with massive hemorrhage activities at your hospital? We would love to hear from you and even feature your hospital work in our newsletter! Suggestions for the provincial toolkit are welcome and can be directed to stephanie.cope@sunnybrook.ca.

Reference:

1. Chin V, Cope S, Hsiung Yeh C, et al. Massive hemorrhage protocol survey: Marked variability and absent in one-third of hospital in Ontario, Canada. Injury, Int. J Care Injured 2019; 50:46-53.