Editing Blood transfusion (section)

=== Inefficacy ===
Transfusion inefficacy or insufficient efficacy of a given unit(s) of blood product, while not itself a "complication" ''per se'', can nonetheless indirectly lead to complications – in addition to causing a transfusion to fully or partly fail to achieve its clinical purpose. This can be especially significant for certain patient groups such as critical-care or neonatals.

For red blood cells (RBC), by far the most commonly transfused product, poor transfusion efficacy can result from units damaged by the so-called storage lesion — a range of biochemical and biomechanical changes that occur during storage. With red cells, this can decrease viability and ability for tissue oxygenation.<ref>{{cite journal | vauthors = Zubair AC | title = Clinical impact of blood storage lesions | journal = American Journal of Hematology | volume = 85 | issue = 2 | pages = 117–122 | date = February 2010 | pmid = 20052749 | doi = 10.1002/ajh.21599 | s2cid = 205293048 | doi-access = free }}</ref> Although some of the biochemical changes are reversible after the blood is transfused,<ref>{{cite journal | vauthors = Heaton A, Keegan T, Holme 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 = 131–6 | date = January 1989 | pmid = 2492818 | doi = 10.1111/j.1365-2141.1989.tb06286.x | s2cid = 43303207 }}</ref> the biomechanical changes are less so,<ref>{{cite journal | vauthors = Frank SM, Abazyan B, Ono M, Hogue CW, Cohen DB, Berkowitz DE, Ness PM, Barodka VM | display-authors = 6 | title = Decreased erythrocyte deformability after transfusion and the effects of erythrocyte storage duration | journal = Anesthesia and Analgesia | volume = 116 | issue = 5 | pages = 975–981 | date = May 2013 | pmid = 23449853 | pmc = 3744176 | doi = 10.1213/ANE.0b013e31828843e6 }}</ref> and rejuvenation products are not yet able to adequately reverse this phenomenon.<ref name="pmid25053933">{{cite journal | vauthors = Barshtein G, Gural A, Manny N, Zelig O, Yedgar S, Arbell D | title = Storage-induced damage to red blood cell mechanical properties can be only partially reversed by rejuvenation | journal = Transfusion Medicine and Hemotherapy | volume = 41 | issue = 3 | pages = 197–204 | date = June 2014 | pmid = 25053933 | pmc = 4086768 | doi = 10.1159/000357986 }}</ref> There has been controversy about whether a given product unit's age is a factor in transfusion efficacy, specifically about 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 | vauthors=Bakalar N | title=The Shelf Life of Donor Blood | date=2013-03-11 | access-date=2013-04-05 | archive-date=2013-03-17 | archive-url=https://web.archive.org/web/20130317014828/http://well.blogs.nytimes.com/2013/03/11/the-shelf-life-of-donor-blood/ | url-status=live }}</ref><ref>{{cite news | url=https://www.wsj.com/articles/SB10001424052748703939404574567771148801570 | work=The Wall Street Journal | title=What's the Shelf Life of Blood? | vauthors=Wang SS | date=2009-12-01 | access-date=2017-08-03 | archive-date=2017-07-09 | archive-url=https://web.archive.org/web/20170709021358/https://www.wsj.com/articles/SB10001424052748703939404574567771148801570 | url-status=live }}</ref> Studies have not been consistent on answering this question,<ref>{{cite journal | vauthors = Aubron C, Nichol A, Cooper DJ, Bellomo R | title = Age of red blood cells and transfusion in critically ill patients | journal = Annals of Intensive Care | volume = 3 | issue = 1 | pages = 2 | date = January 2013 | pmid = 23316800 | pmc = 3575378 | doi = 10.1186/2110-5820-3-2 | doi-access = free }}</ref> with some showing that older blood is indeed less effective but with others showing no such difference;<ref name="z575">{{cite journal | last1=Fergusson | first1=Dean A. | last2=Hébert | first2=Paul | last3=Hogan | first3=Debora L. | last4=LeBel | first4=Louise | last5=Rouvinez-Bouali | first5=Nicole | last6=Smyth | first6=John A. | last7=Sankaran | first7=Koravangattu | last8=Tinmouth | first8=Alan | last9=Blajchman | first9=Morris A. | last10=Kovacs | first10=Lajos | last11=Lachance | first11=Christian | last12=Lee | first12=Shoo | last13=Walker | first13=C. Robin | last14=Hutton | first14=Brian | last15=Ducharme | first15=Robin | last16=Balchin | first16=Katelyn | last17=Ramsay | first17=Tim | last18=Ford | first18=Jason C. | last19=Kakadekar | first19=Ashok | last20=Ramesh | first20=Kuppuchipalayam | last21=Shapiro | first21=Stan | title=Effect of fresh red blood cell transfusions on clinical outcomes in premature, very low-birth-weight infants: the ARIPI randomized trial | journal=JAMA | volume=308 | issue=14 | date=2012-10-10 | issn=1538-3598 | pmid=23045213 | doi=10.1001/2012.jama.11953 | pages=1443–51}}</ref><ref name="f112">{{cite journal | last1=Walsh | first1=Timothy S. | last2=Stanworth | first2=Simon | last3=Boyd | first3=Julia | last4=Hope | first4=David | last5=Hemmatapour | first5=Sue | last6=Burrows | first6=Helen | last7=Campbell | first7=Helen | last8=Pizzo | first8=Elena | last9=Swart | first9=Nicholas | last10=Morris | first10=Stephen | title=The Age of BLood Evaluation (ABLE) randomised controlled trial: description of the UK-funded arm of the international trial, the UK cost-utility analysis and secondary analyses exploring factors associated with health-related quality of life and health-care costs during the 12-month follow-up | journal=Health Technology Assessment  | volume=21 | issue=62 | date=2017 | pmid=29067906 | pmc=5682573 | doi=10.3310/hta21620 | pages=1–118}}</ref> these developments are being closely followed by hospital [[blood bank]]ers — who are the physicians, typically pathologists, who collect and manage inventories of transfusable blood units.

Certain 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, 0.8% in Europe), and a minimum level of post-transfusion RBC survival ''in vivo'' (currently 75% after 24 hours).<ref>{{cite journal | vauthors = Hod EA, Zhang N, Sokol SA, Wojczyk BS, Francis RO, Ansaldi D, Francis KP, Della-Latta P, Whittier S, Sheth S, Hendrickson JE, Zimring JC, Brittenham GM, Spitalnik SL | display-authors = 6 | title = Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation | journal = Blood | volume = 115 | issue = 21 | pages = 4284–92 | date = May 2010 | pmid = 20299509 | pmc = 2879099 | doi = 10.1182/blood-2009-10-245001 }}</ref> However, all of these criteria are applied in a universal manner that does not account for differences among units of product.<ref>{{cite journal | vauthors = Hess JR | title = Scientific problems in the regulation of red blood cell products | journal = Transfusion | volume = 52 | issue = 8 | pages = 1827–35 | date = August 2012 | pmid = 22229278 | doi = 10.1111/j.1537-2995.2011.03511.x | s2cid = 24689742 }}</ref> 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 by itself 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 | vauthors = Pape A, Stein P, Horn O, Habler O | title = Clinical evidence of blood transfusion effectiveness | journal = Blood Transfusion = Trasfusione del Sangue | volume = 7 | issue = 4 | pages = 250–8 | date = October 2009 | pmid = 20011636 | pmc = 2782802 | doi = 10.2450/2008.0072-08 }}</ref> In general, there are not yet any ''in vitro'' tests to assess quality or predict efficacy 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 | 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 | date = May 2012 | pmid = 22043858 | doi = 10.1111/j.1537-2995.2011.03418.x | s2cid = 205724851 }}</ref> and [[erythrocyte fragility]] (mechanical).<ref>{{cite journal | vauthors = Raval JS, Waters JH, Seltsam A, Scharberg EA, Richter E, Daly AR, Kameneva MV, Yazer MH | display-authors = 6 | title = The use of the mechanical fragility test in evaluating sublethal RBC injury during storage | journal = Vox Sanguinis | volume = 99 | issue = 4 | pages = 325–331 | date = November 2010 | pmid = 20673245 | doi = 10.1111/j.1423-0410.2010.01365.x | s2cid = 41654664 }}</ref>

Physicians have adopted a so-called "restrictive protocol" — whereby transfusion is held to a minimum — in part because of the noted uncertainties surrounding storage lesion, in addition to the very high direct and indirect costs of transfusions.<ref name="Missingor">{{cite journal | vauthors = Shander A, Hofmann A, Gombotz H, Theusinger OM, Spahn DR | title = Estimating the cost of blood: past, present, and future directions | journal = Best Practice & Research. Clinical Anaesthesiology | volume = 21 | issue = 2 | pages = 271–289 | date = June 2007 | pmid = 17650777 | doi = 10.1016/j.bpa.2007.01.002 }}</ref><ref>{{cite web
 | title = Transfusion Overuse: Exposing an International Problem and Patient Safety Issue
 | url = https://patientsafetymovement.org/wp-content/uploads/2022/03/Action-Plan-RBC-Overuse-January-13-2013.pdf
 | website = Patient Safety Movement Foundation
 | date = 2013
 | access-date = 15 March 2022
 | archive-date = 1 April 2022
 | archive-url = https://web.archive.org/web/20220401033720/https://patientsafetymovement.org/wp-content/uploads/2022/03/Action-Plan-RBC-Overuse-January-13-2013.pdf
 | url-status = dead
 }}</ref><ref>{{cite web|url=http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=cap_today%2F0409%2F0409d_easy_does_it.html&_state=maximized&_pageLabel=cntvwr |publisher=College of American Pathologists |title=Easy does it — showing caution with RBC transfusions |date=April 2009 |access-date=22 August 2014}}</ref> However, the restrictive protocol is not an option with some especially vulnerable patients who may require the best possible efforts to rapidly restore tissue oxygenation.

Although transfusions of platelets are far less numerous (relative to RBC), platelet storage lesion and resulting efficacy loss is also a concern.<ref>{{cite journal | vauthors = Devine DV, Serrano K | title = The platelet storage lesion | journal = Clinics in Laboratory Medicine | volume = 30 | issue = 2 | pages = 475–487 | date = June 2010 | pmid = 20513565 | doi = 10.1016/j.cll.2010.02.002 }}</ref>