Packed red blood cells

Bag of packed red blood cells.

Names
Other names| Stored packed red blood cells, packed cells, red cell concentrate, red cell component
Clinical data
Routes of
use| IV
Defined daily dose| not established[1]

Packed red blood cells, also known as packed cells, are red blood cells that have been separated for blood transfusion.[2] The packed cells are typically used in anemia that is either causing symptoms or when the hemoglobin is less than usually 70–80 g/L (7–8 g/dL).[2][3][4] In adults, one unit brings up hemoglobin levels by about 10 g/L (1 g/dL).[5][6] Repeated transfusions may be required in people receiving cancer chemotherapy or who have hemoglobin disorders.[2] Cross matching is typically required before the blood is given.[2] It is given by injection into a vein.[7]

Side effects include allergic reactions such as anaphylaxis, red blood cell breakdown, infection, volume overload, and lung injury.[2] With current preparation methods in the developed world the risk of viral infections such as hepatitis C and HIV/AIDS are less than one in a million.[2] However, the risks of infection are higher in low income countries.[8] Packed red blood cells are produced from whole blood or by apheresis.[9] They typically last for three to six weeks.[9]

The widespread use of packed red blood cells began in the 1960s.[10] It is on the World Health Organization's List of Essential Medicines.[11] In the United Kingdom they cost about £120 per unit.[12] A number of other versions also exist including whole blood, leukocyte reduced red blood cells, and washed red blood cells.[2]

## Contents

* 1 Medical uses
* 1.1 Single unit transfusion
* 1.2 Upper gastrointestinal bleeding
* 1.3 Heart surgery
* 1.4 Heart disease
* 1.5 Blood cancers
* 1.6 Transfusion–dependent anemia
* 1.7 Children
* 1.8 Neonates
* 1.9 Dosage
* 2 Side effects
* 3 Compatibility testing
* 4 Collection, processing, and use
* 5 Name
* 6 References
* 7 External links

## Medical uses[edit | edit source]

RBCs are used to restore oxygen-carrying capacity in people with anemia due to trauma or other medical problems, and are by far the most common blood component used in transfusion medicine. Historically they were transfused as part of whole blood, but are now typically used separately as RBCs and plasma components.

More than 100 million units of blood are collected each year around the world, and about 50% of these are given to people in high income countries.[8]

In low-income countries, the majority of blood transfusions (up to 65%) are given to children under 5 years of age to treat severe childhood anemia. Another major use of blood in low income countries is to treat pregnancy-related complications.[8] Whereas in high-income countries, most blood transfusions are given to people over 65 years of age (up to 76%).[8] In these countries transfusion are most commonly used for supportive care in heart surgery, transplant surgery, massive trauma, and therapy for solid and blood cancers.[8] Due to changes in surgical practices, medical use of blood is now the major use of red blood cells in high-income countries.[13]

Whenever a red cell transfusion is being considered for an individual patient it is good practice to consider not only the hemoglobin level, but also the overall clinical context, patient preferences, and whether there are alternative treatments.[3][4] If a person is stable and has a hematinic deficiency they should be treated for the deficiency (iron deficiency, B12 deficiency, or folate deficiency) rather than being given a red cell transfusion.[4]

In adults blood transfusion is typically recommended when hemoglobin levels reach 70 g/L (7 g/dL) in those who have stable vital signs,[3][14] unless they have anemia due to a hematinic deficiency. Transfusing at a restrictive hemoglobin threshold of between 70 g/L to 80 g/L (7 to 8g/dL) decreased the proportion of people given a red blood cell transfusion by 43% across a broad range of clinical specialities, including those people who are critically ill.[3][14] There is no evidence that a restrictive transfusion strategy affects death or major adverse events (e.g. cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy.[3][14] There is not enough information in some patient groups to say whether a restrictive or liberal transfusion threshold is better.[3][14][15][16]

### Single unit transfusion[edit | edit source]

This refers to transfusing a single unit or bag of red blood cells to a person who is not bleeding and haemodynamically stable followed by an assessment to see if further transfusion is required.[17][18] The benefits of single unit transfusion include reduced exposure to blood products. Each unit transfused increases the associated risks of transfusion such as infection, transfusion associated circulatory overload and other side effects.[19][20] Transfusion of a single unit also encourages less wastage of red blood cells.[21]

### Upper gastrointestinal bleeding[edit | edit source]

In adults with upper gastrointestinal bleeding transfusing at a higher threshold caused harm (increased risk of death and bleeding).[22]

### Heart surgery[edit | edit source]

A review established that in patients undergoing heart surgery a restrictive transfusion strategy of 70 to 80g/L (7 to 8g/dL) is safe and decreased red cell use by 24%.[15]

### Heart disease[edit | edit source]

There is less evidence available for the optimal transfusion threshold for people with heart disease, including those who are having a heart attack.[14][15][16] Guidelines recommend a higher threshold for people with heart disease of 80g/L (8 g/dL) if they are not undergoing cardiac surgery.[3][4]

### Blood cancers[edit | edit source]

There is insufficient evidence to suggest how to manage anemia in people with blood cancers in terms of transfusion thresholds.[23]

### Transfusion–dependent anemia[edit | edit source]

People with thalassaemia who are transfusion dependent require a higher hemoglobin threshold to suppress their own red cell production. To do this their hemoglobin levels should not be allowed to drop below 90 to 105g/L (9 to 10.5g/dL).[24]

There is insufficient evidence to recommend a particular hemoglobin threshold in people with myelodysplasia or aplastic anemia,[25] and guidelines recommend an individualized approach to transfusion.[4]

### Children[edit | edit source]

There is less evidence for specific transfusion thresholds in children compared to adults.[14] There has only been one randomized trial assessing different thresholds in children, and this showed no difference between a restrictive or liberal transfusion strategy.[26] This trial used similar thresholds to the adult studies, and transfusing when the hemoglobin is less than 70g/L is also recommended in children.[27]

### Neonates[edit | edit source]

Neonatal red cell transfusion, and when it is appropriate depends on: the gestational age of the baby; how long since the baby had been born; and also on whether the baby is well or ill.[27]

### Dosage[edit | edit source]

The defined daily dose is not established[1]

## Side effects[edit | edit source]

Side effects can include allergic reactions including anaphylaxis, red blood cell breakdown, fluid overload, infection, and lung injury.[2] Giving incompatible RBCs to a person can be fatal.[28]

With current testing methods in high-income countries the risk of infection is very low.[8][29][30] However, in low-income countries the risk of a blood donation being positive for HIV, hepatitis C, or syphilis is approximately 1%, and the risk of it being hepatitis B positive is approximately 4%.[8] Although the World Health Organization recommends that all donated blood is screened for these infections, at least 13 low-income countries are unable to screen all their donated blood for at least one of these infections.[8]

## Compatibility testing[edit | edit source]

To avoid transfusion reactions, the donor and recipient blood are tested, typically ordered as a "type and screen" for the recipient. The "type" in this case is the ABO and Rh type, specifically the phenotype, and the "screen" refers to testing for atypical antibodies that might cause transfusion problems. The typing and screening are also performed on donor blood. The blood groups represent antigens on the surface of the red blood cells which might react with antibodies in the recipient.

The ABO blood group system has four basic phenotypes: O, A, B, and AB. In the former Soviet Union these were called I, II, III, and IV, respectively. There are two important antigens in the system: A and B. Red cells without A or B are called type O, and red cells with both are called AB. Except in unusual cases like infants or seriously immunocompromised individuals, all people will have antibodies to any ABO blood type that isn't present on their own red blood cells, and will have an immediate hemolytic reaction to a unit that is not compatible with their ABO type. In addition to the A and B antigens, there are rare variations which can further complicate transfusions, such as the Bombay phenotype.

The Rh blood group system consists of nearly around 50 different antigens, but the one of the greatest clinical interest is the "D" antigen, though it has other names and is commonly just called "negative" or "positive." Unlike the ABO antigens, a recipient will not usually react to the first incompatible transfusion because the adaptive immune system does not immediately recognize it. After an incompatible transfusion the recipient may develop an antibody to the antigen and will react to any further incompatible transfusions. This antibody is important because it is the most frequent cause of hemolytic disease of the newborn. Incompatible red blood cells are sometimes given to recipients who will never become pregnant, such as males or postmenopausal women, as long as they do not have an antibody, since the greatest risk of Rh incompatible blood is to current or future pregnancies.[31]

For RBCs, type O negative blood is considered a "universal donor" as recipients with types A, B, or AB can almost always receive O negative blood safely. Type AB positive is considered a "universal recipient" because they can receive the other ABO/Rh types safely. These are not truly universal, as other red cell antigens can further complicate transfusions.

There are many other human blood group systems and most of them are only rarely associated with transfusion problems. A screening test is used to identify if the recipient has any antibodies to any of these other blood group systems. If the screening test is positive, a complex set of tests must follow to identify which antibody the recipient has by process of elimination. Finding suitable blood for transfusion when a recipient has multiple antibodies or antibodies to extremely common antigens can be very difficult and time-consuming.

Because this testing can take time, doctors will sometimes order a unit of blood transfused before it can be completed if the recipient is in critical condition. Typically two to four units of O negative blood are used in these situations, since they are unlikely to cause a reaction.[32] A potentially fatal reaction is possible if the recipient has pre-existing antibodies, and uncrossmatched blood is only used in dire circumstances. Since O negative blood is not common, other blood types may be used if the situation is desperate.

## Collection, processing, and use[edit | edit source]

Most frequently, whole blood is collected from a blood donation and is spun in a centrifuge. The red blood cells are denser and settle to the bottom, and the majority of the liquid blood plasma remains on the top. The plasma is separated and the red blood cells are kept with a minimal[clarification needed] amount of fluid. Generally, an additive solution of citrate, dextrose, and adenine is mixed with the cells to keep them alive during storage. This process is sometimes done as automated apheresis, where the centrifuging and mixing take place at the donation site.[33] Most blood banks utilize automated centrifugation systems to wash or volume reduce the blood products they produce and distribute.[34]

The other options is using the person's own blood. This is known as autologous blood transfusion. The person's red blood cells are collected and can be washed by different methods. The two main methods that are used to wash the cells are centrifugation, or filtration methods.[35] The last option is reinfusion without washing. This is the least preferred method because of the chance of complications.[36]

Red blood cells are sometimes modified to address specific needs. The most common modification is leukoreduction, where the donor blood is filtered to remove white cells, although this is becoming increasingly universal throughout the blood supply (over 80% in the US, 100% in Europe). The blood may also be irradiated, which destroys the DNA in the white cells and prevents graft versus host disease, which may happen if the blood donor and recipient are closely related, and is also important for immunocompromized patients. Other modifications, such as washing the RBCs to remove any remaining plasma, are much less common.

With additive solutions, RBCs are typically kept at refrigerated temperatures for up to 45 days.[37] In some patients, use of RBCs that are much fresher is important; for example, US guidelines call for blood less than seven days old to be used for neonatals, to "ensure optimal cell function". However, the phenomenon of RBC storage lesion and its implications for transfusion efficacy are complex and remain controversial (see blood bank and blood transfusion articles).

With the addition of glycerol or other cryoprotectants, RBCs can be frozen and thus stored for much longer (this is not common). Frozen RBCs are typically assigned a ten-year expiration date, though older units have been transfused successfully. The freezing process is expensive and time-consuming and is generally reserved for rare units such as ones that can be used in patients that have unusual antibodies. Since frozen RBCs have glycerol added, the added glycerol must be removed by washing the red blood cells using special equipment, such as the IBM 2991 cell processor in a similar manner to washing RBCs.

The processing (often termed "manufacture", since the end result is deemed a biologic biopharmaceutical product) and the storage can occur at a collection center or a blood bank. RBCs are mixed with an anticoagulant and storage solution which provides nutrients and aims to preserve viability and functionality of the cells (limiting their so-called "storage lesion"), which are stored at refrigerated temperatures for up to 42 days (in the US), except for the rather unusual long-term storage in which case they can be frozen for up to 10 years. The cells are separated from the fluid portion of the blood after it is collected from a donor, or during the collection process in the case of apheresis. The product is then sometimes modified after collection to meet specific patient requirements.

## Name[edit | edit source]

The product is typically abbreviated RBC, pRBC, PRBC, and sometimes StRBC or even LRBC (the latter being to indicate those that have been leukoreduced, which is now true for the vast majority of RBC units). The name "Red Blood Cells" with initial capitals indicates a standardized blood product in the United States.[38] Without capitalization, it is simply generic without specifying whether or not the cells comprise a blood product, patient blood, etc. (with other generic terms for it being "erythrocyte" and "red cell").

## References[edit | edit source]

1. ↑ 1.0 1.1 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 1 July 2021. Retrieved 14 September 2020.
2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Connell NT (December 2016). "Transfusion Medicine". Primary Care. 43 (4): 651–659. doi:10.1016/j.pop.2016.07.004. PMID 27866583.
3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, Gernsheimer T, Holcomb JB, Kaplan LJ, Katz LM, Peterson N, Ramsey G, Rao SV, Roback JD, Shander A, Tobian AA (November 2016). "Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage". JAMA. 316 (19): 2025–2035. doi:10.1001/jama.2016.9185. PMID 27732721.
4. ↑ 4.0 4.1 4.2 4.3 4.4 "Blood transfusion Guidance and guidelines". NICE. Archived from the original on 2016-01-16. Retrieved 2018-09-07.
5. ↑ Plumer, Ada Lawrence (2007). Plumer's Principles and Practice of Intravenous Therapy. Lippincott Williams & Wilkins. p. 423\. ISBN 9780781759441. Archived from the original on 2017-09-14.
6. ↑ Robinson S, Harris A, Atkinson S, Atterbury C, Bolton-Maggs P, Elliott C, Hawkins T, Hazra E, Howell C, New H, Shackleton T, Shreeve K, Taylor C (February 2018). "The administration of blood components: a British Society for Haematology Guideline". Transfusion Medicine. 28 (1): 3–21. doi:10.1111/tme.12481. PMID 29110357.
7. ↑ Linton, Adrianne Dill (2015). Introduction to Medical-Surgical Nursing. Elsevier Health Sciences. p. 287\. ISBN 9781455776412. Archived from the original on 2017-09-14.
8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 "Blood safety and availability". www.who.int. Archived from the original on 2020-04-24. Retrieved 2018-12-20.
9. ↑ 9.0 9.1 Parsons, Polly E.; Wiener-Kronish, Jeanine P. (2012). Critical Care Secrets5: Critical Care Secrets. Elsevier Health Sciences. p. 385\. ISBN 978-0323085007. Archived from the original on 2017-09-14.
10. ↑ Das PC, Smit-Sibinga CT, Halie MR (2012). Supportive therapy in haematology. Springer Science & Business Media. p. 190\. ISBN 9781461325772. Archived from the original on 2017-01-10.
11. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
12. ↑ Yentis, Steven M.; Hirsch, Nicholas P.; Ip, James (2013). Anaesthesia and Intensive Care A-Z: An Encyclopedia of Principles and Practice. Elsevier Health Sciences. p. 147\. ISBN 9780702053757. Archived from the original on 2017-01-12.
13. ↑ Tinegate H, Pendry K, Murphy M, Babra P, Grant-Casey J, Hopkinson C, Hyare J, Rowley M, Seeney F, Watson D, Wallis J (January 2016). "Where do all the red blood cells (RBCs) go? Results of a survey of RBC use in England and North Wales in 2014". Transfusion. 56 (1): 139–45. doi:10.1111/trf.13342. PMID 26442481.
14. ↑ 14.0 14.1 14.2 14.3 14.4 14.5 Carson JL, Stanworth SJ, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC (October 2016). "Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion". The Cochrane Database of Systematic Reviews. 10: CD002042. doi:10.1002/14651858.cd002042.pub4. PMC 4171966. PMID 27731885.
15. ↑ 15.0 15.1 15.2 Carson JL, Stanworth SJ, Alexander JH, Roubinian N, Fergusson DA, Triulzi DJ, Goodman SG, Rao SV, Doree C, Hebert PC (June 2018). "Clinical trials evaluating red blood cell transfusion thresholds: An updated systematic review and with additional focus on patients with cardiovascular disease". American Heart Journal. 200: 96–101. doi:10.1016/j.ahj.2018.04.007. PMID 29898855.
16. ↑ 16.0 16.1 Docherty AB, O'Donnell R, Brunskill S, Trivella M, Doree C, Holst L, Parker M, Gregersen M, Pinheiro de Almeida J, Walsh TS, Stanworth SJ (March 2016). "Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis". BMJ. 352: i1351. doi:10.1136/bmj.i1351. PMC 4817242. PMID 27026510. Archived from the original on 2018-12-20. Retrieved 2018-12-20.
17. ↑ "ISBT: 6. Single unit transfusion". www.isbtweb.org. Archived from the original on 2019-03-06. Retrieved 2019-03-05.
18. ↑ "Single Unit Transfusion Guide | National Blood Authority". www.blood.gov.au. Archived from the original on 2019-03-06. Retrieved 2019-03-05.
19. ↑ Blackstone, Eugene H.; Starr, Norman J.; Loop, Floyd D.; Cosgrove, Delos M.; Mihaljevic, Tomislav; Duncan, Andra I.; Li, Liang; Koch, Colleen (June 2006). "Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting". Critical Care Medicine. 34 (6): 1608–1616. doi:10.1097/01.CCM.0000217920.48559.D8. ISSN 0090-3493. PMID 16607235. Archived from the original on 2019-03-06. Retrieved 2019-03-05.
20. ↑ Guinn, Nicole R.; Maxwell, Cory (2017). "Encouraging single-unit transfusions: a superior patient blood management strategy?". Transfusion. 57 (5): 1107–1108. doi:10.1111/trf.14083. ISSN 1537-2995. PMID 28425603.
21. ↑ Stussi, Georg; Schanz, Urs; Senn, Oliver; Arn, Kornelius; Gerber, Bernhard; Berger, Martin David (2012-01-01). "Significant reduction of red blood cell transfusion requirements by changing from a double-unit to a single-unit transfusion policy in patients receiving intensive chemotherapy or stem cell transplantation". Haematologica. 97 (1): 116–122. doi:10.3324/haematol.2011.047035. ISSN 0390-6078. PMC 3248939. PMID 21933858.
22. ↑ Odutayo, Ayodele; Desborough, Michael J. R.; Trivella, Marialena; Stanley, Adrian J.; Dorée, Carolyn; Collins, Gary S.; Hopewell, Sally; Brunskill, Susan J.; Kahan, Brennan C. (2017). "Restrictive versus liberal blood transfusion for gastrointestinal bleeding: a systematic review and meta-analysis of randomised controlled trials". The Lancet. Gastroenterology & Hepatology. 2 (5): 354–360. doi:10.1016/S2468-1253(17)30054-7. ISSN 2468-1253. PMID 28397699.
23. ↑ Estcourt LJ, Malouf R, Trivella M, Fergusson DA, Hopewell S, Murphy MF (January 2017). "Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support". The Cochrane Database of Systematic Reviews. 1: CD011305. doi:10.1002/14651858.cd011305.pub2. PMC 5298168. PMID 28128441.
24. ↑ "Standards for the clinical care of children and adults with thalassaemia in the UK" (PDF). ukts.org. Archived from the original (PDF) on 2018-12-14. Retrieved 2018-12-20.
25. ↑ Gu Y, Estcourt LJ, Doree C, Hopewell S, Vyas P (October 2015). "Comparison of a restrictive versus liberal red cell transfusion policy for patients with myelodysplasia, aplastic anaemia, and other congenital bone marrow failure disorders". The Cochrane Database of Systematic Reviews (10): CD011577. doi:10.1002/14651858.cd011577.pub2. PMC 4650197. PMID 26436602.
26. ↑ Lacroix, Jacques; Hébert, Paul C.; Hutchison, James S.; Hume, Heather A.; Tucci, Marisa; Ducruet, Thierry; Gauvin, France; Collet, Jean-Paul; Toledano, Baruch J. (2007-04-19). "Transfusion strategies for patients in pediatric intensive care units". The New England Journal of Medicine. 356 (16): 1609–1619. doi:10.1056/NEJMoa066240. ISSN 1533-4406. PMID 17442904. Archived from the original on 2021-08-28. Retrieved 2019-01-05.
27. ↑ 27.0 27.1 New, Helen V.; Berryman, Jennifer; Bolton‐Maggs, Paula H. B.; Cantwell, Carol; Chalmers, Elizabeth A.; Davies, Tony; Gottstein, Ruth; Kelleher, Andrea; Kumar, Sailesh (2016). "Guidelines on transfusion for fetuses, neonates and older children". British Journal of Haematology. 175 (5): 784–828. doi:10.1111/bjh.14233. ISSN 1365-2141. PMID 27861734.
28. ↑ "Complications of Transfusion: Transfusion Medicine: Merck Manual Professional". Archived from the original on 23 October 2010. Retrieved 3 November 2011.
29. ↑ PHB Bolton-Maggs (Ed) D Poles et al. on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group. The 2017 Annual SHOT Report (2018).https://www.shotuk.org/wp-content/uploads/myimages/SHOT-Report-2017-WEB-Final-v3-02-8-18.pdf
30. ↑ "Diseases and Organisms | Blood Safety | CDC". www.cdc.gov. 2017-07-18. Archived from the original on 2018-09-07. Retrieved 2018-09-07.
31. ↑ "Guidelines for Blood Component Substitution in Adults" (PDF). Provincial Blood Coordinating Program, Newfoundland and Labrador. Archived from the original (PDF) on 14 April 2012. Retrieved 3 November 2011.
32. ↑ "The appropriate use of group O RhD negative red cells" (PDF). National Health Service. Archived from the original (PDF) on 29 April 2012. Retrieved 3 November 2011.
33. ↑ "Circular of information for the use of human blood and blood components" (PDF). AABB. p. 11\. Archived from the original (PDF) on 30 October 2011. Retrieved 3 November 2011.
34. ↑ Lu, Madeleine; Lezzar, Dalia L.; Vörös, Eszter; Shevkoplyas, Sergey S. (2019-01-03). "Traditional and emerging technologies for washing and volume reducing blood products". Journal of Blood Medicine. 10: 37–46. doi:10.2147/JBM.S166316. PMC 6322496. PMID 30655711. Archived from the original on 2020-01-29. Retrieved 2020-01-29.
35. ↑ Lu, Madeleine; Lezzar, Dalia L.; Vörös, Eszter; Shevkoplyas, Sergey S. (2019-01-03). "Traditional and emerging technologies for washing and volume reducing blood products". Journal of Blood Medicine. 10: 37–46. doi:10.2147/JBM.S166316. PMC 6322496. PMID 30655711.
36. ↑ Liumbruno, Giancarlo Maria; Waters, Jonathan H. (July 2011). "Unwashed shed blood: should we transfuse it?". Blood Transfusion. 9 (3): 241–245. doi:10.2450/2011.0109-10. ISSN 1723-2007. PMC 3136589. PMID 21627923.
37. ↑ "Circular of information for the use of human blood and blood components" (PDF). AABB. p. 8\. Archived from the original (PDF) on 30 October 2011. Retrieved 3 November 2011.
38. ↑ "21 CFR 640.10". GPO. Archived from the original on 26 October 2011. Retrieved 3 November 2011.

## External links[edit | edit source]

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