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==Storage and management== [[File:Blood Research- Saving Lives (8384) (9759061442).jpg|thumb|Whole blood is often separated, using a centrifuge, into components for storage and transportation.]] Routine blood storage is 42 days or 6 weeks for stored packed ''red blood cells'' (also called "StRBC" or "pRBC"), by far the most commonly transfused blood product, and involves refrigeration but usually not freezing. There has been increasing controversy about whether a given product unit's age is a factor in transfusion efficacy, specifically on whether "older" blood directly or indirectly increases risks of complications.<ref>{{cite news | url=http://well.blogs.nytimes.com/2013/03/11/the-shelf-life-of-donor-blood/ | work=The New York Times | first=Nicholas | last=Bakalar | title=The Shelf Life of Donor Blood | date=2013-03-11 | url-status=live | archive-url=https://web.archive.org/web/20130317014828/http://well.blogs.nytimes.com/2013/03/11/the-shelf-life-of-donor-blood/ | archive-date=2013-03-17 }}</ref><ref>{{cite news | url=https://www.wsj.com/articles/SB10001424052748703939404574567771148801570 | work=The Wall Street Journal | title=What's the Shelf Life of Blood? | first=Shirley S. | last=Wang | date=2009-12-01 | url-status=live | archive-url=https://web.archive.org/web/20170709021358/https://www.wsj.com/articles/SB10001424052748703939404574567771148801570 | archive-date=2017-07-09 }}</ref> Studies have not been consistent on answering this question,<ref>{{cite journal|title=Age of red blood cells and transfusion in critically ill patients|first1=Cécile|last1=Aubron|first2=Alistair|last2=Nichol|first3=D. Jamie|last3=Cooper|first4=Rinaldo|last4=Bellomo|journal=Annals of Intensive Care|volume=3|issue=1|pages=2|doi=10.1186/2110-5820-3-2|pmid = 23316800|pmc=3575378|year = 2013 |doi-access=free }}</ref> with some showing that older blood is indeed less effective but with others showing no such difference; nevertheless, as storage time remains the only available way to estimate quality status or loss, a ''first-in-first-out'' inventory management approach is standard presently.<ref>{{cite web|url=http://www.healthleadersmedia.com/page-2/QUA-289788/Bloods-Shelf-Life-May-Be-as-Short-as-3-Weeks|title=Blood's Shelf Life May Be as Short as 3 Weeks |website=www.healthleadersmedia.com|access-date=4 May 2018|url-status=dead|archive-url=https://web.archive.org/web/20141205063056/http://www.healthleadersmedia.com/page-2/QUA-289788/Bloods-Shelf-Life-May-Be-as-Short-as-3-Weeks|archive-date=2014-12-05}}</ref> It is also important to consider that there is large ''variability'' in storage results for different donors, which combined with limited available quality testing, poses challenges to clinicians and regulators seeking reliable indicators of quality for blood products and storage systems.<ref name="NIH 22229278">{{Cite journal | last1 = Hess | first1 = J. R. | author2 = Biomedical Excellence for Safer Transfusion (BEST) Collaborative | doi = 10.1111/j.1537-2995.2011.03511.x | title = Scientific problems in the regulation of red blood cell products | journal = Transfusion | volume = 52 | issue = 8 | pages = 1827–35 | year = 2012 | pmid = 22229278 | s2cid = 24689742 }}</ref> Transfusions of ''platelets'' are comparatively far less numerous, but they present unique storage/management issues. Platelets may only be stored for 7 days,<ref>{{cite web |url=https://www.fda.gov/OHRMS/DOCKETS/ac/02/briefing/3839b2_02_platelets.htm |title=Storage of Platelets out to 7 days |website=[[Food and Drug Administration]] |access-date=2013-04-01 |url-status=dead |archive-url=https://web.archive.org/web/20130221091710/https://www.fda.gov/OHRMS/DOCKETS/ac/02/briefing/3839b2_02_platelets.htm |archive-date=2013-02-21 }}</ref> due largely to their greater potential for contamination, which is in turn due largely to a higher storage temperature. ===RBC storage lesion=== Insufficient transfusion efficacy can result from red blood cell (RBC) blood product units damaged by so-called ''storage lesion''—a set of biochemical and biomechanical changes which occur during storage. With red cells, this can decrease viability and ability for tissue oxygenation.<ref>{{cite journal|last1=Zubair|first1=AC|title=Clinical impact of blood storage lesions.|journal=American Journal of Hematology|date=February 2010|volume=85|issue=2|pages=117–22|doi=10.1002/ajh.21599|pmid=20052749|doi-access=free}}{{open access}}</ref> Although some of the biochemical changes are reversible after the blood is transfused,<ref>{{Cite journal | doi = 10.1111/j.1365-2141.1989.tb06286.x | last1 = Heaton | first1 = A. | last2 = Keegan | first2 = T. | last3 = Holme | first3 = S. | title = In vivo regeneration of red cell 2,3-diphosphoglycerate following transfusion of DPG-depleted AS-1, AS-3 and CPDA-1 red cells | journal = British Journal of Haematology | volume = 71 | issue = 1 | pages = 131–36 | year = 1989 | pmid = 2492818| s2cid = 43303207 }}</ref> the biomechanical changes are less so,<ref>{{cite journal|last1=Frank|first1=SM|last2=Abazyan|first2=B|last3=Ono|first3=M|last4=Hogue|first4=CW|last5=Cohen|first5=DB|last6=Berkowitz|first6=DE|last7=Ness|first7=PM|last8=Barodka|first8=VM|title=Decreased erythrocyte deformability after transfusion and the effects of erythrocyte storage duration.|journal=Anesthesia and Analgesia|date=May 2013|volume=116|issue=5|pages=975–81|doi=10.1213/ANE.0b013e31828843e6|pmid=23449853|pmc=3744176}}</ref> and rejuvenation products are not yet able to adequately reverse this phenomenon.<ref>{{cite web |url=http://www.isb-isch2012.org/Poster/P32.htm |title=Improvement of hemodynamic function and mechanical properties of stored red blood cells by "rejuvenation" treatment |website=www.isb-isch2012.org |access-date=22 May 2022 |archive-url=https://archive.today/20130415021739/http://www.isb-isch2012.org/Poster/P32.htm |archive-date=15 April 2013 |url-status=usurped}}</ref> Current regulatory measures are in place to minimize RBC storage lesion—including a maximum shelf life (currently 42 days), a maximum auto-hemolysis threshold (currently 1% in the US), and a minimum level of post-transfusion RBC survival ''in vivo'' (currently 75% after 24 hours).<ref>{{cite journal|title=Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation|first1=Eldad A.|last1=Hod|first2=Ning|last2=Zhang|first3=Set A.|last3=Sokol|first4=Boguslaw S.|last4=Wojczyk|first5=Richard O.|last5=Francis|first6=Daniel|last6=Ansaldi|first7=Kevin P.|last7=Francis|first8=Phyllis|last8=Della-Latta|first9=Susan|last9=Whittier|first10=Sujit|last10=Sheth|first11=Jeanne E.|last11=Hendrickson|first12=James C.|last12=Zimring|first13=Gary M.|last13=Brittenham|first14=Steven L.|last14=Spitalnik|date=27 May 2010|journal=Blood|volume=115|issue=21|pages=4284–92|doi=10.1182/blood-2009-10-245001|pmid=20299509|pmc=2879099}}</ref> However, all of these criteria are applied in a universal manner that does not account for differences among units of product;<ref name="NIH 22229278"/> for example, testing for the post-transfusion RBC survival ''in vivo'' is done on a sample of healthy volunteers, and then compliance is presumed for all RBC units based on universal (GMP) processing standards. RBC survival does not guarantee efficacy, but it is a necessary prerequisite for cell function, and hence serves as a regulatory proxy. Opinions vary as to the best way to determine transfusion efficacy in a patient ''in vivo''.<ref>{{cite journal | pmc = 2782802 | pmid=20011636 | doi=10.2450/2008.0072-08 | volume=7 | issue=4 | title=Clinical evidence of blood transfusion effectiveness | date=October 2009 |vauthors=Pape A, Stein P, Horn O, Habler O | journal=Blood Transfus | pages=250–58}}</ref> In general, there are not yet any ''in vitro'' tests to assess quality deterioration or preservation for specific units of RBC blood product prior to their transfusion, though there is exploration of potentially relevant tests based on RBC membrane properties such as [[erythrocyte deformability]]<ref>{{cite journal |vauthors=Burns JM, Yang X, Forouzan O, Sosa JM, Shevkoplyas SS | date = May 2012 | title = Artificial microvascular network: a new tool for measuring rheologic properties of stored red blood cells | journal = Transfusion | volume = 52 | issue = 5| pages = 1010–23 | doi=10.1111/j.1537-2995.2011.03418.x | pmid=22043858| s2cid = 205724851 }}</ref> and [[erythrocyte fragility]] (mechanical).<ref>{{cite journal|last1=Raval|first1=JS|last2=Waters|first2=JH|last3=Seltsam|first3=A|last4=Scharberg|first4=EA|last5=Richter|first5=E|last6=Daly|first6=AR|last7=Kameneva|first7=MV|last8=Yazer|first8=MH|title=The use of the mechanical fragility test in evaluating sublethal RBC injury during storage.|journal=Vox Sanguinis|date=November 2010|volume=99|issue=4|pages=325–31|doi=10.1111/j.1423-0410.2010.01365.x|pmid=20673245|s2cid=41654664}}</ref> Many physicians have adopted a so-called "restrictive protocol"—whereby transfusion is held to a minimum—due in part to the noted uncertainties surrounding storage lesion, in addition to the very high direct and indirect costs of transfusions,<ref name=directions/> along with the increasing view that many transfusions are inappropriate or use too many RBC units.<ref>{{cite web |url=http://www.patientsafetysummit.org/_assets/documents/Action%20Plan%20-%20RBC%20Overuse%20-%20January%2013,%202013.pdf |title=Archived copy |website=www.patientsafetysummit.org |access-date=22 May 2022 |archive-url=https://web.archive.org/web/20181005184056/http://www.patientsafetysummit.org/_assets/documents/Action%20Plan%20-%20RBC%20Overuse%20-%20January%2013,%202013.pdf |archive-date=5 October 2018 |url-status=dead}}</ref><ref>{{cite web|url=http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=/portlets/contentViewer/show&_windowLabel=cntvwrPtlt&cntvwrPtlt%7BactionForm.contentReference%7D=cap_today/0409/0409d_easy_does_it.html&_state=maximized&_pageLabel=cntvwr|title=Easy does it – showing caution with RBC transfusions|website=College of American Pathologists|access-date=4 May 2018|url-status=dead|archive-url=https://web.archive.org/web/20180504232110/http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt%7BactionForm.contentReference%7D=cap_today%2F0409%2F0409d_easy_does_it.html&_state=maximized&_pageLabel=cntvwr|archive-date=2018-05-04}}</ref> ===Platelet storage lesion=== Platelet storage lesion is a very different phenomenon from RBC storage lesion, due largely to the different functions of the products and purposes of the respective transfusions, along with different processing issues and inventory management considerations.<ref>{{Cite journal | last1 = Devine | first1 = D. V. | last2 = Serrano | first2 = K. | doi = 10.1016/j.cll.2010.02.002 | title = The Platelet Storage Lesion | journal = Clinics in Laboratory Medicine | volume = 30 | issue = 2 | pages = 475–87 | year = 2010 | pmid = 20513565 }}</ref> ===Alternative inventory and release practices=== Although as noted the primary inventory-management approach is first in, first out (FIFO) to minimize product expiration, there are some deviations from this policy—both in current practice as well as under research. For example, exchange transfusion of RBC in neonates calls for use of blood product that is five days old or less, to "ensure" optimal cell function.<ref>{{cite web |url=http://www.imj.ie/Archive/IMJ%20June%2007%20Supplement.pdf |title=Archived copy |access-date=2013-04-03 |url-status=dead |archive-url=https://web.archive.org/web/20130412081559/http://www.imj.ie/Archive/IMJ%20June%2007%20Supplement.pdf |archive-date=2013-04-12 }}</ref> Also, some hospital blood banks will attempt to accommodate physicians' requests to provide low-aged RBC product for certain kinds of patients (e.g. cardiac surgery).<ref>Handbook of Pediatric Transfusion Medicine, edited by Ronald Strauss, Naomi Luban; Ch. 2, p. 12.</ref> More recently, novel approaches are being explored to complement or replace FIFO. One is to balance the desire to reduce average product age (at transfusion) with the need to maintain sufficient availability of non-outdated product, leading to a strategic blend of FIFO with last in, first out (LIFO).<ref>{{Cite journal | pmid = 21756261| year = 2012| last1 = Atkinson| first1 = M. P.| title = A novel allocation strategy for blood transfusions: Investigating the tradeoff between the age and availability of transfused blood| journal = Transfusion| volume = 52| issue = 1| pages = 108–17| last2 = Fontaine| first2 = M. J.| last3 = Goodnough| first3 = L. T.| last4 = Wein| first4 = L. M.| doi = 10.1111/j.1537-2995.2011.03239.x| hdl = 10945/48003| s2cid = 15257457| url = https://calhoun.nps.edu/bitstream/10945/48003/1/Atkinson-a-novel%20%289%29.pdf}}</ref> ===Long-term storage=== "Long-term" storage for all blood products is relatively uncommon, compared to routine/short-term storage. [[Cryopreservation]] of red blood cells is done to store rare units for up to ten years.<ref>{{cite web|title=Circular of Information for the use of Human Blood and Blood Components |page=16 |publisher=[[American Association of Blood Banks|AABB]], [[American Red Cross|ARC]], [[America's Blood Centers]] |url=http://www.aabb.org/Documents/About_Blood/Circulars_of_Information/coi0702.pdf |access-date=2010-10-18 |url-status=dead |archive-url=https://web.archive.org/web/20091007071259/http://www.aabb.org/Documents/About_Blood/Circulars_of_Information/coi0702.pdf |archive-date=October 7, 2009 }}</ref> The cells are incubated in a [[glycerol]] solution which acts as a [[cryoprotectant]] ("antifreeze") within the cells. The units are then placed in special sterile containers in a freezer at very low temperatures. The exact temperature depends on the glycerol concentration.
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