Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C •...
Transcript of Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C •...
![Page 1: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/1.jpg)
Extending the Shelf Life of Thawed Cryoprecipitate
BBTS conference 19th September 2019
Lucy BowerComponent Development LaboratoryNHS Blood and Transplant, Cambridge, UK
![Page 2: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/2.jpg)
Name of NHSBT speaker and conference title
Coagulation
• Mechanism by which blood forms a clot
• Part of haemostasis (process that stops bleeding)
• Complex cascade of reactions – Cross linked fibrin
• Strengthens the initial platelet plug
![Page 3: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/3.jpg)
Name of NHSBT speaker and conference title
Coagulation cascade
![Page 4: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/4.jpg)
Name of NHSBT speaker and conference title
Coagulation cascade
![Page 5: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/5.jpg)
Name of NHSBT speaker and conference title
Coagulation cascade
![Page 6: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/6.jpg)
Name of NHSBT speaker and conference title
Coagulation cascade
![Page 7: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/7.jpg)
Name of NHSBT speaker and conference title
Cryoprecipitate
• Frozen blood component manufactured from Fresh Frozen Plasma (FFP)
• High in fibrinogen, FVIII, FXIII, vWF and fibronectin
• Used in the UK as a source of fibrinogen
![Page 8: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/8.jpg)
Name of NHSBT speaker and conference title
Manufacture
• Slow thaw for 16 hours at 2-6°C
• Centrifugation
• Removal of the supernatant –Not used in the UK
• ~50mL cryoprecipitate (Single)
• 5 units for pooled cryoprecipitate
![Page 9: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/9.jpg)
Name of NHSBT speaker and conference title
Use of cryoprecipitate
• Used in trauma / major haemorrhage for the treatment of acquired hypofibrinogenemia– Low fibrinogen levels and coagulopathy have been associated with
inferior outcomes in major haemorrhage
• Fibrinogen supplementation has been shown to improve outcomes
• Early administration of fibrinogen may improve survival from major haemorrhage? (CRYOSTAT-II)
![Page 10: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/10.jpg)
Name of NHSBT speaker and conference title
Current challenge• Cryoprecipitate requires ambient storage
– Reprecipitation of proteins
• Post thaw shelf life limited to 4 hours– Bacteriology risk
• Not pre thawed
• Thawing on demand may delay availability
• Short shelf life increases wastage
![Page 11: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/11.jpg)
Name of NHSBT speaker and conference title
Post thaw ambient cryoprecipitate data
Green/Backholer et al. Transfusion 2016; 56:1356-1361
• Fg and FXIII stable for up to 72 hours• Significant decrease in FVIII after 24 hours• Bacteriology risk unquantified
![Page 12: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/12.jpg)
Name of NHSBT speaker and conference title
Storage at 4°C
• Lower bacteriology risk
• FFP 5 day PT storage at 4°C for major haemorrhage
• Storage at 4°C causes reprecipitation of coagulation proteins– Reconstitute with 37°C warm
![Page 13: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/13.jpg)
Name of NHSBT speaker and conference title
• 5 minute “warm” cycle to reconstitute precipitate• 4 hrs at RT post warm
Study design
WastageRapid
availability
![Page 14: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/14.jpg)
Name of NHSBT speaker and conference title
Fibrinogen
Storage % of starting (post thaw)
72 hr 102.9
120 hr 104.1
![Page 15: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/15.jpg)
Name of NHSBT speaker and conference title
FVIII
Storage % of starting (post thaw)
72 hr 84.4
120 hr 82.4
![Page 16: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/16.jpg)
Name of NHSBT speaker and conference title
FXIII
Storage % of starting (post thaw)
72 hr 99.9
120 hr 96.6
![Page 17: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/17.jpg)
Name of NHSBT speaker and conference title
Additional quality analysis
• vWF analysis
• Overall component efficacy– In vitro model of coagulopathy
• Is the fibrin network effected by reprecipitation?– Fibrin network analysis- Confocal microscopy
![Page 18: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/18.jpg)
Name of NHSBT speaker and conference title
Alternatives / Clinical trials
• Fibrinogen concentrate (FC) – Lyophilised, viral inactivated and known concentration– Not licensed in UK for acquired deficiencies
• Ongoing clinical studies:– FC v Cryoprecipitate (FEISTY, FIBRES)
• Possible advantages with cryoprecipitate– Other coagulation factors may provide clinical benefit?– Studies may not answer this
![Page 19: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/19.jpg)
Name of NHSBT speaker and conference title
Summary
• 4°C post thaw storage appears feasible
• Initial quality data looks acceptable
• Bacteria spiking study required– Very little data currently available
![Page 20: Extending the Shelf Life of Thawed Cryoprecipitate€¦ · • Slow thaw for 16 hours at 2-6°C • Centrifugation • Removal of the supernatant –Not used in the UK • ~50mL cryoprecipitate](https://reader035.fdocuments.in/reader035/viewer/2022070205/60f6fc53d37e1b072f1d1f47/html5/thumbnails/20.jpg)
Name of NHSBT speaker and conference title
Acknowledgements
• Rebecca Cardigan & The Component Development Laboratory
• NBL & Manufacturing Colindale, NHSBT • Hospital Services Cambridge • Laura Green/Sean Platton & Barts
Health NHS Trust• Simon Stanworth