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Red blood cells (RBCs)

  • Red blood cells (RBCs), also named erythrocytes, are derived from the haemopoietic stem cells in the bone marrow
  • The most common disorders associated with RBC are anaemias, characterised by low oxygen transport capacity of the blood
  • Blood transfusions are associated with potential risks, such as infections, fever, allergic reactions, transfusion-related acute lung injury, transfusion-associated circulatory overload, and iron overload
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RBC transfusion

RBC transfusions are necessary to increase patients’ oxygen transport capacity.4 Blood is often transfused when patients have anaemia, are experiencing active bleeding or during surgery. However, blood products are a scare resource as they must be produced from an eligible blood donor after extensive screening and testing for suitability and to minimise the potential of transfusion-transmitted diseases. 

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Figure 2: Labelled blood bag

Patient blood management (PBM) is a multidisciplinary and evidence-based approach to optimise the care of patients who might need transfusions. Optimised PBM programmes have been shown to be effective at reducing the need for RBC transfusions, thus reducing the requirement for this finite resource and the risks associated with use of donor blood products.5 PBM encompasses all aspects of the transfusion decision-making process, beginning with the initial patient evaluation and continuing through clinical management.6 This approach can be applied in any situations where blood loss may occur and the World Health Organization (WHO) has recommended the implementation of PBM as best practice.7 

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Figure 3: The three pillars of patient blood management for improving outcomes 

Red blood cells

Red blood cells (RBCs), also named erythrocytes, are derived from the haemopoietic stem cells in the bone marrow. Following different maturation steps, they enucleate and enter the blood circulation. Their main role is to transport oxygen from the lungs to the tissues to act as the final electron acceptor in the generation of adenosine triphosphate (ATP) through oxidative phosphorylation, and to transport the waste product, carbon dioxide, back to the lungs for exhalation.1,2 The most common disorders associated with RBCs are anaemias, which are characterised by low oxygen transport capacity of the blood and subsequent lack of oxygen in the tissues. 

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Figure 1: Image of a red blood cell

The role of red blood cells in haemostasis

New evidence has indicated major roles for RBCs in haemostasis, particularly blood clotting.3  RBCs play a role in the contraction of blood clots by platelets, with the resulting densely packed erythrocytes forming and almost impermeable barrier essential for haemostasis and wound healing.3  RBCs also interact with fibrinogen to regulate clod formation.  Therefore, RBCs are potential targets for the treatment of haemostatic disturbances. 

Risks associated with allogenic blood transfusions

Organisms.  Despite the meticulous qualification process and safety checks in place, blood transfusions are still associated with potential risks, such as infections, fever, allergic reactions, transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload, venous and arterial thrombotic events, and iron overload, which can lead to increased morbidity and mortality in critically ill patients. 8,9  The risk of these occurring increases with the number of RBC units transfused, and may be greater with blood that has been stored longer as ageing RBCS are inducers of oxidative stress, which can lead to inflammation and lung disease damage.10

Infectious

Organisms such as bacteria, viruses, prions, and parasites can be transmitted through blood transfusions. Infectious complications from blood transfusions have decreased over the past years due to improved donor questionnaires and sophisticated blood screening.11In particular virus screening as improved with pathogens such as hepatitis and human immunodeficiency virus (HIV) routinely screened for before in potential blood donors. As the presence of bacteria is not routinely tested in eligible blood donor, transmission of bacteria through blood transfusions is much more frequent than viruses and bacteria are the leading cause of death in transfusion transmitted infections.12 

Non-Infectious

Non-infectious serious hazards of transfusion (NISHOTs) are currently the most frequent forms of complications of transfusion. NISHOTs include everything from well-described and categorized transfusion reactions (hemolytic, febrile, septic, and allergic/urticarial/anaphylactic) to lesser known complications.11

Non-infectious complications can be classified as acute and delayed reactions based on time of occurrence and further subclassified as immune or non-immune. Additionally, RBC and platelet transfusions is associated with increased risk of venous and arterial thrombotic events, however the causality of this relationship is still to be determined.8

Table 1. Non-infectious complications.

 Acute Reaction (<24 hours)

Delayed Reaction (>24 hours)

Immune-mediated reactions

Non-immune mediated reactions

Immune-mediated reactions

Non-immune mediated reactions

Acute hemolytic transfusion reaction (AHTR)

Air embolism

Delayed hemolytic transfusion reaction (DHTR)

Iron overload

Febrile nonhemolytic transfusion reaction (FNHTR)

Transfusion-associated circulatory overload (TACO)

Alloimmunization

- To HLA antigens

- To platelet antigens

- To red cell antigens

Allergic reactions

Allergic reactionsNon-immune hemolysis

Transfusion-related immunomodulation (TRIM)

Anaphylactic reactions Transfusion-associated graft versus host disease (TA-GVHD) 
Transfusion-related acute lung injury (TRALI)

 Post-transfusion purpura (PTP)

 

Post-transfusion alloimmunisation is the main complication observed after one or more RBCs concentrates transfusions, also sometimes observed after platelet concentrates transfusions.13 Alloimmunization refers to an immune response to foreign antigens from another human and may be followed by clinical complications.
Increased incidence of postoperative infection and risk of cancer recurrence in patients who have received allogeneic blood transfusions suggests that transfusions might be associated with clinically significant immunomodulatory effects (TRIM).14
Given these risks, it is therefore advisable to minimize allogenic RBC transfusion where possible. Once potential strategy for this during surgical bleeding is by cell salvage. 

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References

References

  1. Klinken SP. Red Blood Cells. Int J Biochem Cell Biol. Dec 2002;34(12):1513-8. doi:10.1016/s1357-2725(02)00087-0
  2. Kuhn V, et al. Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia. Antioxid Redox Signal. May 1 2017;26(13):718-742. doi:10.1089/ars.2016.6954
  3. Alamin AA. The Role of Red Blood Cells in Hemostasis. Semin Thromb Hemost. Feb 2021;47(1):26-31. doi:10.1055/s-0040-1718889
  4. Tanhehco YC. Red Blood Cell Transfusion. Clin Lab Med. Dec 2021;41(4):611-619. doi:10.1016/j.cll.2021.07.004
  5. Murphy MF, et al. The Scientific Basis for Patient Blood Management. Transfus Clin Biol. Aug 2015;22(3):90-6. doi:10.1016/j.tracli.2015.04.001
  6. News & Resources. Patient Blood Management. Accessed July 2023, https://www.aabb.org/news-resources/resources/patient-blood-management#:~:text=Patient%20blood%20management%20(PBM)%20is,and%20continuing%20through%20clinical%20management.
  7. World Health Organization. The Urgent Need to Implement Patient Blood Management: Policy Brief. Accessed August 2023, https://www.who.int/publications/i/item/9789240035744
  8. Napolitano LM, et al. Clinical Practice Guideline: Red Blood Cell Transfusion in Adult Trauma and Critical Care. J Trauma. Dec 2009;67(6):1439-42. doi:10.1097/TA.0b013e3181ba7074
  9. Khorana AA, et al. Blood Transfusions, Thrombosis, and Mortality in Hospitalized Patients with Cancer. Arch Intern Med. Nov 24 2008;168(21):2377-81. doi:10.1001/archinte.168.21.2377
  10. Lee JS, et al. Bad Blood: The Risks of Red Cell Storage. Nat Med. Apr 2010;16(4):381-2. doi:10.1038/nm0410-381
  11. Hendrickson JE, et al. Noninfectious Serious Hazards of Transfusion. Anesth Analg. Mar 2009;108(3):759-69. doi:10.1213/ane.0b013e3181930a6e
  12. Pelletier, JPR. Infectious Complications of Transfusion of Blood Components. Clinical Principles of Transfusion Medicine. Mar 23 2018;Chapter 8:85–92. doi: doi: 10.1016/B978-0-323-54458-0.00008-8. Epub 2018 Mar 23
  13. Garraud O, et al. An Overview of Red Blood Cell and Platelet Alloimmunisation in Transfusion. Transfus Clin Biol. Nov 2022;29(4):297-306. doi:10.1016/j.tracli.2022.08.140
  14. Blumberg N. Allogeneic Transfusion and Infection: Economic and Clinical Implications. Semin Hematol. Jul 1997;34(3 Suppl 2):34-40.