1. NAC Irradiation Working Group
Update – D Morrison & S Stopera
April 28, 2016

2. Members of the Irradiation WG (March 31, 2016)
Dana Devine
Debra Lane
Doug Morrison – WG Chair
Brian Muirhead – NAC Chair
Susan Nahirniak
Lakshmi Rajappannair
Nancy Robitaille-Guest
Vincent Laroche-Guest
Wendy Peppel
Shelley Stopera – NAC Coordinator

3. Health Canada Regulations
Clause 80
An establishment that irradiates blood must do so in accordance with sections to of the Standard.

4. CSA Z902 – 2015
Clause 11.7
The transfusion service shall have a written policy indicating which recipients or categories of recipients are to receive irradiated cellular blood components. See Clauses 7.12 and The transfusion service shall have a written policy with respect to permitted storage periods for irradiated blood components.

5. Indications for Irradiation (at risk patients) - Primarily based upon BCSH 2010 and ANZSBT 2011 guidelines and informed by expert opinion - Agreed upon most indications as described in BCSH guidelines - Need for consensus on neonatal transfusions, B-cell malignancies (NHL) and which immunosuppressive medications

6. Irradiation Practices in
NAC – 2016 National Survey
Irradiation Practices in
Neonatal Transfusion

7. Survey Overview
Survey was sent to 23 L3 – NICU contacts provided by CBS
5 Non responses
3 unsolicited responses
2 additional responses from QC
Total survey responses analyzed is 23

8. 22 – Level 3
1 – Level 2 (in MB)
23 – Total

10. Intrauterine Transfusions23
Institutions
Perform IUT
Do not perform IUT
Provide Irradiated Blood

11. Neonatal Exchange Transfusions23
Institutions
Perform Exchange
Do not perform Exchange
Provide Irradiated Blood all Neonates regardless of weight
Provide Irradiated Blood for ET in Neonates less than 1200g at birth
Provide Irradiated Blood for ET in Neonates less than 1500g at birth 19
Provide Irradiated Blood to post IUT ET

12. Top-up transfusions - Assumption
Applies to all the options above

13. Neonatal Top - Up Transfusions23
Institutions
Perform Top-up
Provide Irradiated Blood to all Neonates regardless of birth weight
Provide Irradiated Blood to Neonates less than 1200g at birth
Provide Irradiated Blood to Neonates less than 1500g at birth 22
Provide Irradiated Blood to post IUT

15. 9 Irradiate blood on Site23
Institutions
Irradiate blood on Site
Do Not Perform Manipulation to reduce Potassium
Perform Manipulation to reduce Potassium
Do Not Irradiate blood on Site (receive Irradiated from Off - Site)
Have Rules restricting Age of the Blood
Have Rules restricting Length of the Storage
Have Rules restricting both Age of the Blood and Length of the Storage
Did not Reply

16. Irradiation related Complications
Did Not have complications related to Hyperkalemia
Hyperkalemia in the context of a top-up transfusion 23
Institutions
1 out of Had a case of TA-GVHD
Had complications related to Hyperkalemia
Hyperkalemia in the context of a large volume transfusion or multiple top-up

20. Di George Syndrome - testing for 22q11.2 deletion
Neonates with congenital heart defects should receive irradiated blood until 6 months?
Di George Syndrome - testing for 22q11.2 deletion

21. NAC WG consensus recommendations on irradiation for IUT and neonatal transfusions
Intrauterine transfusion1,2,3;
Exchange transfusions if there has been a previous IUT or if the donation comes from a first- or second-degree relative1,2,3 and for other ET if it does not unduly delay transfusion2,3;
Neonatal Top-Up transfusions
if there has been a previous IUT1,2,3 and for
very low birth weight neonates (less than 1200g) 1,3;
ANZSBT 2011
“Top-up transfusion: It is not necessary to irradiate cellular components for routine „top-up‟ transfusions unless there has either been a previous intrauterine transfusion or the blood has come from a blood relative, in which case the cellular component must be irradiated.”
However, their recommendations include the following
Clinical considerations:
“Premature neonates: Particular consideration should be given to providing irradiated cellular components for premature infants <28 weeks or <900g, and consideration should also be given to using irradiated cellular blood components in premature infants weighing less than 1300g and,
All neonates: Consideration should be given when possible to use of irradiated cellular components transfused to newborns.
ANZSBT 2011
BCSH 2010
NAC WG expert opinion

22. NAC WG consensus recommendations on irradiation for IUT and neonatal transfusions
Irradiated blood components are not required for emergency transfusions of unmatched group O, D-negative red cells in neonates;
Irradiated blood components are indicated for life in neonates confirmed to be 22q11.2 deletion syndrome1,2,3;
Irradiated blood components are indicated for neonates with complex cardiac abnormalities until 22q11.2 deletion syndrome has been excluded3.
ANZSBT 2011
BCSH 2010
NAC WG expert opinion

23. CSA Z902 – 2015
Clause
Irradiated blood and red blood cells shall have a maximum expiration time of 28 days after irradiation
or shall retain the original outdate, whichever is shorter.
Table 2 includes:  “a shorter outdate may apply to irradiated blood intended for transfusion for neonates”

24. CSA Z902 – 2015
Clause
For irradiated products for intrauterine or neonatal recipients, in addition to the requirements of Clauses 7.12 and 11.7, there shall be a written policy with respect to permitted storage periods for irradiated blood components.

25. Effect of Irradiation on RBC - The quality or red cell concentrates (K+ & free Hgb) is affected by the age of blood at the time of irradiation and the length of storage post-irradiation - NAC WG is recommending voluntary alignment with Council of Europe standards, BCSH and Australia-New-Zealand guidelines

26. Hemolysis levels are influenced by age at irradiation and length of storage after irradiation
988 RCC in SAGM….Serrano et al. Vox Sang 2013

27. Alignment with Council of Europe Standards
CSA Clause
Irradiated blood and red blood cells shall have a maximum expiration time of 28 days after irradiation or shall retain the original outdate, whichever is shorter.
COE Standard – 17th Ed. 2013
Red cell components may be irradiated up to 28 days after collection. Irradiated cells must be transfused as soon as possible, but no later than 14 days after irradiation, and, in any case, no later than 28 days after collection.

28. Alignment with ANSBT & BCSH Guidelines
ANSBT 2011 Red cells may be irradiated at any time up to 14 days after collection and, thereafter, stored for a further 14 days from irradiation. Where the patient is at particular risk from hyperkalemia, it is recommended that red cells be transfused within 24 hours of irradiation. BCSH 2010 Red cells may be irradiated at any time up to 14 d after collection , and thereafter may be stored for a further 14 d. Where the patient is at particular risk from hyperkalemia (e.g. IUT or ET) it is recommended that the red cells be transfused within 24h of irradiation or that the cells are washed.
Need to assess impact on CBS inventory of adopting these more restrictive recommendations

29. NAC WG Practice Recommendations – March 31, 2016
If storage of pre-irradiated inventory is necessary, obtain red cells that have been irradiated within 14 days of collection.
If irradiation is performed between 14 and 28 days of collection, it should be transfused ASAP and no later than 7 days after irradiation.
Irradiation of red cells more than 28 days post collection should only be performed immediately prior to use.

30. NAC WG Practice recommendations for management of inventory – March 31, 2016
Prolonged storage of pre-irradiated units is associated with high potassium levels, in-vitro hemolysis and decreased post-transfusion recovery.
Maintaining large inventories of irradiated RCC results in transfusion of irradiated RCC to patients who do not require irradiated RCC.
Proactive inventory management must take into consideration the perceived risk of TA-GVHD in the local patient population, the risks of transfusing irradiated red cells to patients who do not require irradiated cellular components and the logistics of providing irradiated components for elective transfusions.
For elective transfusions reliance on a regional hub site for on-demand irradiation or pre-irradiated stock is recommended.

31. NAC WG Inventory Discussion – March 31, 2016
Over stocking of pre-irradiated units for emergency transfusion is not recommended.
Observational evidence from SHOT suggests that pre-storage universal leukoreduction has reduced the risk of TA-GVHD.
A recent systematic review (Kopolovic 2015) of 348 cases of TA-GVHD found that greater than 93.4% of cases were associated with non-leukoreduced components. When reported, 94% of were associated with components less than 10 days old.
In the event of emergency transfusion in the absence of on-site irradiation or pre-storage irradiated inventory, leukoreduced red cells that have been stored for more than 14 days will significantly reduce the risk of TA-GVHD.
Emerging data suggests that leukoreduction may reduce the risk of TA-GVHD.

32. Lymphoma & related B-cell malignancies
Some jurisdictions in Canada & elsewhere (Ruhl 2009) include all patients with lymphoma
Consultation with a Canadian expert in Lymphoma (Joseph Connors)
Impossible to reliably identify a subset of lymphoma patients who are severely immunocompromised due to their therapy or advanced stage of their disease.
Favors “all or none” – willing to accept statement from TM experts “none”
BCSH and ANZSBT guidelines are clear for patients receiving nucleoside analogues
Some jurisdictions are able to access medication history
NAC WG preference to deal with this question in the context of immunosuppressive medications

33. Irradiation WG Next Steps
WG members to review recent literature in general and for immunosuppressive medications.
Refine recommendations regarding NHL and related B-cell malignancies.
Assess impact on CBS & HQ of COE standards vs BCSH/ANZSBT guidelines on age of RCC and post-irradiation expiry.
Refine inventory management recommendations
Finalize recommendations for approval by NAC and the CBS PT BLC