1. CSTM Annual Conference
May 2015
NAC updates
Brian Muirhead FRCPC
NAC Chair

2. NAC
No financial or other relevant disclosures to reveal
Dr. Brian Muirhead .

3. Evolution of the NAC
The National Technical Working Group (NTWG) was created to provide medical and technical advice on the utilization management of blood and blood products to the provincial and territorial (PT) Ministries of Health and Canadian Blood Services (CBS) through the Deputy Ministers’ Policy Advisory Committee on Blood and Blood Products (DMPAC).
The DMPAC was disbanded and at this time the NTWG reported to the Provincial Territorial Blood Liaison Committee (PT BLC). As the relationship between the PT and CBS matured, this reporting structure was expanded to include Canadian Blood Services CBS PT BLC. Subsequently, the NTWG was renamed National Advisory Committee (NAC). .

4. Mandate of NAC
The National Advisory Committee on Blood and Blood Products (NAC) shall collaborate with and provide advice on the utilization management of blood and blood products and transfusion medicine practice to the provincial and territorial (PT) Ministries of Health and Canadian Blood Services (CBS).
The NAC shall take direction from and report to the CBS/PT Blood Liaison Committee.

5. Membership
The CBS/PT Blood Liaison Committee and CBS shall appoint representatives to the NAC as follows:
Each PT may appoint two representatives from either of the following categories:
a health care professional with experience in transfusion medicine or expertise in blood utilization management
Ministry of Health personnel with primary responsibility for blood resource management.
CBS shall appoint four representatives
Non-voting members to include co-chairs of the CBS/PT Blood Liaison Committee

6. Members – 2015 May Shelley Stopera NAC Coordinator
Dr. Brian Muirhead, Chair Manitoba
Dr. Robert Coupland British Columbia
Dr. Doug Morrison British Columbia
Dr. Susan Nahirniak Alberta
Dr. Meer-Taher Shabani-Rad Alberta
Dr. Debra Lane Manitoba
Dr. Katerina Pavenski Ontario
Dr. Alan Tinmouth Ontario
Dr. Vincent Laroche Québec
Dr. David Anderson Nova Scotia
Dr. Irene Sadek Nova Scotia
Dr. Jennifer Fesser Prince Edward Island
Dr. Lakshmi Rajappannair New Brunswick
Dr. Lucinda Whitman Newfoundland and Labrador
Dr. Dana Devine Canadian Blood Services
Mr. Rick Trifunov Canadian Blood Services
Dr. Kathryn Webert Canadian Blood Services
Dr. Ted Alport Canadian Blood Services
Lindy McIntyre, Ex-Officio Canadian Blood Services
Wendy Peppel, Ex-Officio Manitoba
Shelley Stopera
NAC Coordinator

7. Funding
NAC is funded by the Provincial / Territorial Blood Liaison Committee (PT BLC).
This money is administered by the Blood Portfolio Lead Province
NAC lead generally changes on a 2 year rotation with the PT BLC.

8. Lead Provinces
A number of provinces have hosted the NAC, since it’s inception; BC, NS, AB, NL, NB with MB being the current Lead Province.
With the support of a full-time coordinator and countless volunteer hours contributed by it’s members (and working groups) the NAC has developed a number of guidance and recommendation documents.
The NAC is an important resource for transfusion medicine in Canada and now let’s look at some significant highlights of their important collaborative work to date…………………

9. Inventory Management Process
The National Plan for the Management of Shortages of Labile Blood Components
The Plan
Emergency Framework
Inventory Planning
3 Components to Inventory Management

10. The National Plan for the Management of Shortages of Labile Blood Components
This plan was approved by the Deputy Ministers of Health in December 2009
Ongoing Improvements
National simulation November lessons learned to be included in next iteration
March 2015 survey - to evaluate the National planning completed by Canadian Blood Services as the result of a potential OPSEU strike.
The Plan is a ‘living’ document and as such is reviewed regularly for continuous improvements.

11. National Blood Shortages Plan
CBS PT Blood Liaison Committee
NAC
NAC Blood Shortages Working Group
Inventory Planning Working Group
Stakeholder feedback
Approval and Support
General Revisions
National Blood Shortages Plan
Recommendations

12. Inventory Management Process
Emergency Framework for rationing of Blood for massively bleeding patients during a red phase of a blood shortage
The Plan
Emergency Framework
Inventory Planning
3 Components to Inventory Management

13. Emergency framework for rationing of blood for massively bleeding patients during a red phase of a blood shortage
This document was developed to help guide Physicians to triage patients in need of massive transfusion during a red phase shortage.
Support of PT Ministers of Health Sept 27, 2012
A document “synopsis for triage teams” was also developed by this committee. This document was incorporated verbatim into provincial / regional / hospital blood shortage contingency plans.
This document is currently under revisions. During the November 2013 Simulation, 3 Hospitals validated, over a 4 day period, the framework for the rationing document during a red phase to see how much RBCs would be saved by following the National Plan for Management of Shortages of Labile Blood Components.

14. Inventory Management Process
Blood Shortage Working Group
Inventory Planning
The Plan
Emergency Framework
Inventory Planning
3 Components to Inventory Management

15. National Shortages Plan
Provincial / Territorial
Canadian Blood Services
Blood Liaison Committee
National Advisory Committee
on Blood
and Blood Products (NAC)
NAC Blood Shortage
Working Group
(NAC BSWG)
Communications
Inventory Planning
Emergency Framework for Rationing
Blood to Massively Bleeding Patients
During a Red Phase Blood Shortage
To explore and address blood product inventory issues in relation to the ‘National Plan for the Management of Labile Blood Components’. Specifically appropriate hospital inventory levels reflective of the various national blood level phases identified in the National plan.
National Shortages Plan

16. BSWG - Inventory Planning
CBS/PTBLC supports the concept of a transparent national inventory with unique blood system indicators based on the collection of certain standard data elements. This is a necessary step for the National Plan to function effectively during normal operations and during shortage.
Improved CBS Inventory Levels at Green, Amber and Red Phases.
- This data along with the provision for Hospitals to enter inventory levels into the Inventory Level webpage within the CBS Blood Component and Product Disposition system will enable assessment of TOTAL blood product inventories (blood supplier and hospital combined) across the country in near to real time criteria.
Manitoba and BC have provincial reporting strategies which have been taken into consideration in assessing the reporting of inventory -- some jurisdictions have unique challenges to using the CBS reporting system.

17. Guidelines / Recommendations

18. IVIG Guidelines Guidelines on the use of intravenous immune globulin
for hematologic conditions
for neurologic conditions
for Primary Immune Deficiencies
for solid organ transplantation
The NAC supports the use of an adjusted body weight calculator to calculate IVIG dosing in adult patients. A recommendation for the use of one single calculator cannot be made until sufficient data is gathered and reviewed.

19. IVIG Guidelines Reviews
The guidelines for the use of IVIG (for hematologic/for neurologic conditions) have not been reviewed for a considerable period of time and given the rapid progress of research in the field these guidelines are currently under review to maintain their credibility among treating physicians.

20. Recombinant Factor VIIa
In 2006, NAC developed a transfusion policy framework for the use of off-label recombinant FVIIa in massive bleeding. Review of the policy framework in 2011
Transfusion policy framework for the use of off-label
recombinant FVIIa in massive bleeding developed in 2006.
Review of the policy by Dr. Yulia Lin et al on behalf of NAC done in 2011
Reviewed by NAC in 2015-

21. Prothrombin Complex Concentrates
Recommendations for Use of Prothrombin Complex Concentrates (octaplex® and Beriplex®) in Canada’
The PCC Working Group was formed to gather support and/or recommend revisions to these national recommendations in consideration of available evidence, literature, cost-effective utilization, management of PCC products and optimization of patient care.

22. PCC recommendations supported by available evidence or rationale.
Document revised May 2014, highlights include:
Clarifications –use of oral vitamin K
6 hour rationale
Vitamin K dosing / routes of administration
Target INR
Rationale around the various targets
Dosing
No Consensus; Options provided
PCC videos posted ( providing a guide to the National Advisory Committee guidelines in the use of Prothrombin Complex Concentrates for warfarin reversal.

23. Solvent Detergent Plasma
Framework for appropriate use and distribution of solvent detergent treated plasma
Approved for funding in 2011.
Framework posted 2012
In consultation with the NAC, P/T BLC CBS has extended the approval period for SD Plasma requests for patients to 12 months.
Revised Framework January 2015

24. Transfusion Policy Framework for RBC Transfusion
NAC endorsed the AABB Red cell transfusion guidelines and wrote a companion document to:
Emphasize salient points from the AABB guidelines
Emphasize not relying solely on transfusion triggers
Highlight recent advances in the literature
Identify additional tools (implementation, data collection)
Red Blood Cell Transfusion Policy Framework – A Companion Document to the AABB Guidelines – posted to website May 2014

25. National Recipient Advisory Committee
Specific Recommendations re:
Post Donation Information
Technical Manufacturing Issues
Bacterial Contamination
TRALI
Revisions are made annually to update risk tables

26. National Recipient Advisory Committee
Primary vs. Secondary NRAC
CBS COO Chief supply chain officer, NAC Chair & Vice-Chair, CBS VP Med/Scientific/Research Affairs, Blood portfolio Lead province rep
Proposed role of Primary NRAC in a large recall situation:
Discuss if recipient notification required
Determine if secondary NRAC will convene
Develop strategies and next steps for consideration and discussion by the secondary NRAC

28. Recipient Recall Notification contd…..
The National Recipient Advisory Committee was convened during the past 2 years:
CMV recall – August 2013, due to a CMV testing issue, products from specific clinics recalled. Recipient notification recommended.
Calgary recall – December 2013, due to a manufacturing error, products recalled. Recipient notification not recommended.

29. STATEMENTS

30. CMV safe and CMV sero negative products
The requirements for CMV negative versus CMV safe blood components has been under review for the last several years.
Discussions concentrated on the marked provincial variability in demand for CMV tested components in Canada and the trends/policies for the provision of CMV tested products implemented internationally.
Due to lack of sufficient evidence to support national consensus, NAC prepared a statement re: use of CMV safe and CMV sero negative products

31. CMV safe and CMV sero negative products
August 20, NAC’s statement regarding appropriateness of use of Cytomegalovirus (CMV) sero negative vs CMV safe product
"The National Advisory Committee recommends that CMV safe and CMV IgG seronegative products be considered equivalent for the majority of patient populations including adult and pediatric Hematopoietic stem cell recipients, CMV seronegative patients who may require future transplant and immunodeficient patients. Due to significant controversy and lack of evidence on the need for the provision of CMV seronegative products, in addition to leukodepletion, in the following 3 patient groups - intrauterine transfusion, neonates under 28 days of age and in elective transfusion of CMV seronegative pregnant women, NAC recommends to follow local policies".

32. Reversal of ‘new’ anticoagulants
November 2014
Reversal of Direct Oral Anticoagulants (DOACs) - Direct Thrombin Inhibitors (i.e.Dabigatran) and Direct Factor Xa Inhibitors (i.e.Rivaroxaban or Apixaban).
Although anecdotal reports and animal studies have been published using plasma protein products for reversal of Direct Oral Anticoagulants, at this time there is still no study in humans using clinical bleeding outcomes as an endpoint that has evaluated any reversal agent.
With this lack of evidence for dosing, safety and efficacy of these agents the National Advisory Committee on Blood and Blood Products (NAC) cannot develop a recommendation for use of prothrombin complex concentrates, FEIBA or recombinant Factor VIIa in the reversal of Direct Thrombin or Direct Factor Xa Inhibitors. The administration of Frozen plasma or Vitamin K will not be of any benefit in the setting of DOAC associated bleeding unless other concomitant coagulopathy is present.

33. Reversal of ‘new’ anticoagulants

34. Fibrinogen (RiaSTAP) Fibrinogen Concentrates - FC (RiaSTAP) –
Recommendations for the use of FC for indications of acquired hypofibrinogenemia which are not identified in the product monograph were initiated Fall 2014.
Due to limited literature available, the working group advised NAC to post a statement rather than a recommendation. December 2015.

35. Fibrinogen (RiaSTAP)
While there is evidence that fibrinogen replacement plays an important role in management of bleeding post cardiac surgery or trauma as well as in obstetrical hemorrhage, there is still uncertainty as to the optimal fibrinogen replacement product or dose. Fibrinogen concentrate (FC), frozen plasma (FP), and cryoprecipitate are currently used to treat acquired hypofibrinogenemia.
Fibrinogen content of the above mentioned products is as follows:
1 vial FC = – 1.3 g fibrinogen
1000 ml FP= / g fibrinogen (1 SD)
1 unit cryoprecipitate= / g fibrinogen (2 SD)

36. Fibrinogen (RiaSTAP)
Optimal dosing of the above mentioned products is unclear as it is affected by:
The inter-donor variability of fibrinogen content in blood components/products
Patient’s unique clinical situation, including patient’s baseline fibrinogen level and a situation-appropriate fibrinogen target
At this time, there is insufficient evidence of superiority of FC over FP or cryoprecipitate. Until the results of on-going trials are known, NAC cannot recommend FC over other means of fibrinogen replacement as the preferred method of replacing fibrinogen in acquired hypofibrinogenemia in a bleeding patient.

37. Work in progress…..
Previously noted (Signal Detection Analysis) for the IVIG guidelines (hematologic and neurologic conditions), underway. This analysis will help in determining which clinical conditions within the guidelines there may be requirement for updating etc.
Recommendations for Irradiated Blood and Blood Components

38. New Blood Products

39. Process for New Blood Products
Blood product manufacturers submit application to Health Canada
Notice of Compliance issued by Health Canada
Canadian Blood Services requests NAC to perform a Medical Review, when applicable
Provinces and Territories decide on funding approach
Unless requested by the PT-CBS Blood Liaison Committee, NAC will not generate frameworks or recommendations around new product implementation

40. New Blood Products
Several products have been reviewed by NAC as part of the CBS Plasma Products Selection Process.
A few recent ones are…
Factor IX product AlprolixTM (November 2014)
Factor XIII: EloctateTM (March 2015)