Red Cells

Aka. Red Blood Cells (RBCs), Packed Red Blood Cells (PRBCs), Red Petrol

DESCRIPTION

• Human red blood cell product for transfusion

INDICATIONS

1. For treatment of clinically significant anaemia with a symptomatic deficit of oxygen-carrying capacity
2. Replacement of medical, traumatic or surgical blood loss (please see below for specific transfusion thresholds)

ADMINISTRATION / DOSING

• Intravenous (IV)
• Adults:
  • Each unit raises haemoglobin levels by approximately 10 g/L
• Children (from Lifeblood and RCH guidelines):
  •  <20kg and >20kg: Volume to be transfused = 0.5 x patient weight (kg) x (desired Hb(g/L) – patient’s current Hb(g/L))
  • An alternative is to administer 10-15 mL/kg (up to one unit, then reassess)
• Neonates please see RCH guidelines
• Administration:
  • Administer as fast as required, however, the unit must be completed within 4 hours of removal from controlled storage
  • Transfuse through blood administration set incorporating a standard 170-200 µm filter (most pump sets include a 200 µm filter)

PREPARATION

• Collected at donation centres throughout Australia after a strict screening program for donors
• Whole blood is initially collected into a bag containing a solution of CPD (Citrate phosphate dextrose, see below for further breakdown)
• Whole blood is then sent through a centrifuge removing most of the plasma after centrifuging whole blood collected into another anticoagulant (Citrate-based)
• The red cells may then be resuspended in other additives (such as SAG-M or SAG-M2 for washed cells) to prolong storage and are filtered to remove most leucocytes
• Paediatric units are made by dividing a single unit of red cells into four packs of equal volume for the purpose of reducing donor exposure for small paediatric transfusions and minimising wastage.
• Modifications (see Modifications to blood components):
  • Phenotyped
  • Washed red cells
  • CMV Seronegative
  • Frozen red cells
  • Irradiated
  • Intrauterine Transfusion (IUT)

PHARMACEUTICS

• Presentation:
  • Whole blood (WB) red cells leucodepleted
    • Volume: 260 (+/- 15) mL
  • WB paediatric red cells leucodepleted (set of 4)
    • Volume: 60 (+/- 4) mL
  • WB washed red cells leucodepleted
    • Volume: 258 (+/- 18) mL
• Contents:
  • Red cells (leucocyte depleted)
    • Haemoglobin: 48 (+/- 5) g/unit
    • Haematocrit: 0.58 (+/- 0.03) L/L
    • Haemolysis: 0.3 (+/- 0.1) % at expiry date
    • Leucocyte count: 0.02 (+/- 0.07) x10⁶/unit
  • Red cells paediatric (leucocyte depleted)
    • Haemoglobin: N/A – initial unit prior to splitting > 40 g/unit
    • Haematocrit: 0.61 (+/- 0.04) L/L
    • Haemolysis: 0.2 (+/- 0.1) % at expiry date
    • Leucocyte count: N/A, initial unit prior to splitting <1.0 x10⁶/unit
  • Red cells washed (leucocyte depleted)
    • Haemoglobin: 48 (+/- 5) g/unit
    • Haematocrit: 0.62 (+/- 0.03) L/L
    • Haemolysis: 0.1 (+/- 0.1) % at expiry date
    • Leucocyte count: N/A, initial unit prior to splitting <1.0 x10⁶/unit
    • Last wash supernatant: 0.02 (+/- 0.03) total protein g/unit
• Excipients:
  • CPD (Citrate phosphate dextrose)
    • Sodium citrate dihydrate 26.3 g/L – 1.75 g (per pack)
    • Citric acid monohydrate 3.27 g/L – 0.22 g (per pack)
    • Monobasic sodium phosphate dihydrate 2.51 g/L – 0.17 g (per pack)
    • Dextrose monohydrate 25.5 g/L – 1.70 g (per pack)
  • SAG-M (Saline adenine glucose mannitol)
    • Sodium chloride 8.77 g/L – 0.92 g (per pack)
    • Adenine 0.169 g/L – 0.02 g (per pack)
    • Dextrose monohydrate 9.0 g/L – 0.95 g (per pack)
    • Mannitol 5.25 g/L – 0.55 g (per pack)
  • SAG-M2 (washed red cell additive)
    •  Sodium chloride 8.77 g/L – 0.877 g (per pack)
    • Adenine 0.169 g/L – 0.03 g (per pack)
    • Dextrose monohydrate 8.18 g/L – 0.818 g (per pack)
    • Mannitol 5.25 g/L – 0.525 g (per pack)
• Storage:
  • At 2^oC – 6^oC a shelf-life of 42 days, the answer to the great question of life, the universe, and everything.
    • Shelf-life of the paediatric units is 35 days with the appropriate additives
  • Time outside controlled storage conditions prior to commencing transfusion should not be longer than 30 min

GROUP / CROSSMATCH

• Identical ABO and RhD group to the recipient must be used
• However, O- red cells must be used in an emergency when the recipients’ blood group is not known (and O+ blood in men / post-menopausal women)
• See CCC page on Blood Product Compatibility

ADVERSE EFFECTS

• Please see transfusion risks / reactions
• Early
  • FeverAllergy: Mild –> AnaphylaxisAir embolismHypothermiaAcute haemolytic reactionTRALI (Transfusion-related acute lung injury)Volume Overload (Transfusion Associated Circulatory Overload — TACO)
  • Citrate Toxicity
• Late
  • Viral infection
  • Bacterial infection
  • Parasitic infection:
  • Prion infection:
  • GVHD (Graft versus Host Disease)
  • Immune sensitisation (Rh D antigen)
  • TRIM (Transfusion-related immunomodulation)

MECHANISM OF ACTION

• Red blood cells are small (6-8µm), flexible biconcave discs and haemoglobin is a protein inside red cells
• Haemoglobin is the workhorse of blood, carrying ~98% of the oxygen (and ~23% of carbon dioxide) around the body
• Looking at the oxygen-carrying capacity of blood equation:
• DO₂ = CO X ((BO₂ X ceHb X sO₂) + (PaO₂ x 0.03))
  • DO₂ = Rate of oxygen delivery in mL/minCO = Cardiac output in mL/min
  • BO₂ = maximum oxygen-carrying capacity of the blood (mL/g of Hb). Normally 1.39 mL/g
  • ceHb = Concentration of effective haemoglobin in g/L (i.e. excluding dyshaemoglobin species)
  • sO₂ = Percentage saturation of haemoglobin expressed as a fraction (i.e. 97% = 0.97)
  • PaO₂ = Partial pressure of oxygen in mmHg
  • 0.03 mL/L/mmHg = solubility constant for oxygen at 37^oC
    • Only ~2% of oxygen is dissolved in the plasma

CONTRAINDICATIONS

• Do not use if the patient objects to red cells being administered, e.g. patients who identify as being a Jehovah’s Witness
• Do not use if anaemia can be treated with specific medications such as: Iron, vitamin B12, folic acid or erythropoietin

TRANSFUSION TARGETS

Adults

• These targets are taken from Patient Blood Management Guidelines: Module 4 – released in 2012
• Critically ill patients
  • Hb <70 g/L
    • RBC transfusion may be indicated, however, may not be required in well-compensated patients or where other therapy is available
  • Hb 70-90 g/L
    • RBC transfusion is not associated with reduced mortality
    • RBC transfusion decision should be based on the need to relieve clinical signs and symptoms of anaemia
  • Hb >90 g/L
    • RBC transfusion is generally unnecessary
• Patients with Acute Coronary Syndrome (ACS)
  • Hb <80 g/L
    • RBC transfusion may be associated with reduced mortality
  • Hb 80-100 g/L
    • Effect of transfusion on mortality is uncertain and may be associated with an increased recurrence of myocardial infarction
  • Hb >100 g/L
    • Not advisable because of an association with increased mortality

Paediatrics (refer to RCH Guideline)

• Hb <70 g/L
  • RBC transfusion often indicated, however lower thresholds may be acceptable in patients without symptoms and where specific therapy (e.g. iron) is available
• Hb <70-90 g/L
  • RBC transfusion may be indicated depending on the clinical setting, e.g. haemolysis, bleeding, or clinical signs and/or symptoms of anaemia
• Hb >90 g/L
  • RBC transfusion often unnecessary and may be inappropriate
• Other targets:
  • Children with cyanotic congenital heart disease or on ECMO
  • Children with haemoglobinopathies (thalassaemia or sickle cell disease) or on a chronic transfusion program

Neonatal (please see RCH Guideline)

EVIDENCE

• REALITY Trial (2021 – JAMA): RCT, European setting, n = 668
  • P – AMI and anaemia (Hb 70-100 g/L)
  • I – Liberal transfusion for Hb <100 g/L w/ target of >110 g/L
  • C – Restrictive transfusion for Hb <80 g/L w/ target of 80-100 g/L
  • O – No difference at 30 days for MACE outcomes, however trend of harm in liberal group w/ acute lung injury and infection
    • Issues: Not powered for superiority trial, short follow-up period of 30 days
  • The Bottom Line Review
• TRICS III (2017 – NEJM): RCT, 19 countries, 37 sites, n = 4860
  • P – Restrictive vs liberal transfusion strategy in >18 y/o patients undergoing cardiac surgery with moderate-to-high risk of death
  • I – Restrictive group transfusion threshold: Hb < 75 g/L intra- or post-operatively
  • C – Liberal group transfusion threshold: Hb <95 g/L intraoperatively and Hb <85 g/L in non-ICU ward
  • O – Restrictive threshold was non-inferior to liberal for death, myocardial infarct, new onset renal failure requiring dialysis. Secondary outcomes including LOS / ventilation etc. all did not reach statistical significance.
  • The Bottom Line Review
    • Follow up data at 6 months – restrictive still non-inferior. TBLR
• TRICOP Trial (2017 – Critical Care Medicine): RCT, single centre in Brazil, n = 300
  • P – Adult oncology patients with septic shock
  • I – Restrictive strategy with transfusion threshold Hb <70 g/L
  • C – Liberal strategy with transfusion threshold Hb  <90 g/L
  • O – All cause mortality at 28 days, no significant difference.
  • The Bottom Line Review
• TRISS Trials Group (2014 – NEJM): RCT, 32 Scandinavian ICUs, n = 998
  • P – Adult patients with septic shock and Hb <90 g/L
  • I – Restrictive transfusion threshold of <70 g/L
  • C – Liberal transfusion threshold of <90 g/L
  • O – Primary outcome all cause mortality at 90 days, no significant difference
  • The Bottom Line Review
• Villanueva (2013 – NEJM): RCT, single centre Spain, n = 921
  • P – Any upper GI bleed­ (who also received scope within 6 hours +/- somatostatin +/-prophylactic antibiotics +/- definitive mgmt. of bleeding point)
  • I – Restrictive strategy, threshold <70 g/L w/ target of 70-90 g/L
  • C – Liberal strategy, threshold of <90 g/L w/ target of 90- 110 g/L
  • O – All cause mortality at 45 days 5% in restrictive arm vs 9% in liberal group
    • Notes: Restrictive a possibility IF early source control with scope achievable
  • The Bottom Line Review
• TRICC Investigators (1999 – NEJM): RCT, 25 sites in Canada, n = 838
  • P – Adult patients admitted to the ICU
  • I – Restrictive transfusion threshold of Hb <70 g/L
  • C – Liberal transfusion threshold of Hb <90 g/L
  • O – No significant difference in all cause 30 day mortality
  • The Bottom Line Review

References and Links

CCC Transfusion Series
Blood Products	Cryoprecipitate, Fresh Frozen Plasma (FFP), Platelets, Red Cells (RBCs) Concentrates: Prothrombinex, Factor VIIa, Fibrinogen Concentrate
Reversal	Rivaroxaban / Apixaban / Enoxaparin: Andexanet Alfa, Rivaroxaban and Bleeding Dabigatran: Idarucuzimab, Dabigatran and bleeding Heparin: Protamine Warfarin: Vitamin K / FFP / PTx, Warfarin Reversal, Warfarin Toxicity
Testing	Coagulation Studies, TEG / ROTEM (Thromboelastography), Platelet function assays
General Topics	Acute Coagulopathy of Trauma, Blood Bank, Blood conservation strategies, Blood Product Compatibilities, Blood transfusion risks, Disseminated Intravascular Coagulation, Massive blood loss, Massive transfusion protocol (MTP), Modifications to blood components,Procedures and Coagulopathy, Storage Lesions, TRALI, Transfusion Literature Summaries, Transfusion Reactions

Essential resource

Patient Blood Management Guidelines from the National Blood Authority of Australia

References

• Australian Red Cross Lifeblood. (2020, June). Blood Component Information: An Extension of Blood Component Labels. Retrieved January 18, 2023, from https://www.lifeblood.com.au/sites/default/files/resource-library/2021-12/78.-Blood_Component_Information_1.pdf
• Bergamin FS, Almeida JP, Landoni G, Galas FRBG, Fukushima JT, Fominskiy E, Park CHL, Osawa EA, Diz MPE, Oliveira GQ, Franco RA, Nakamura RE, Almeida EM, Abdala E, Freire MP, Filho RK, Auler JOC Jr, Hajjar LA. Liberal Versus Restrictive Transfusion Strategy in Critically Ill Oncologic Patients: The Transfusion Requirements in Critically Ill Oncologic Patients Randomized Controlled Trial. Crit Care Med. 2017 May;45(5):766-773. doi: 10.1097/CCM.0000000000002283. PMID: 28240687.
• Chambers, D., Huang, C.L.-H. and Matthews, G. (2015) “7 – Oxygen Transport, 8 – Carbon Dioxide Transport, 68 – Transfusion,” in Basic physiology for Anaesthetists. Cambridge: Cambridge University Press.
• Ducrocq G, Gonzalez-Juanatey JR, Puymirat E, Lemesle G, Cachanado M, Durand-Zaleski I, Arnaiz JA, Martínez-Sellés M, Silvain J, Ariza-Solé A, Ferrari E, Calvo G, Danchin N, Avendaño-Solá C, Frenkiel J, Rousseau A, Vicaut E, Simon T, Steg PG; REALITY Investigators. Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Clinical Trial. JAMA. 2021 Feb 9;325(6):552-560. doi: 10.1001/jama.2021.0135. PMID: 33560322; PMCID: PMC7873781. [Free Full Text]
• Hébert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999 Feb 11;340(6):409-17. doi: 10.1056/NEJM199902113400601. Erratum in: N Engl J Med 1999 Apr 1;340(13):1056. PMID: 9971864. [Free Full Text]
• Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, Johansson PI, Aneman A, Vang ML, Winding R, Nebrich L, Nibro HL, Rasmussen BS, Lauridsen JR, Nielsen JS, Oldner A, Pettilä V, Cronhjort MB, Andersen LH, Pedersen UG, Reiter N, Wiis J, White JO, Russell L, Thornberg KJ, Hjortrup PB, Müller RG, Møller MH, Steensen M, Tjäder I, Kilsand K, Odeberg-Wernerman S, Sjøbø B, Bundgaard H, Thyø MA, Lodahl D, Mærkedahl R, Albeck C, Illum D, Kruse M, Winkel P, Perner A; TRISS Trial Group; Scandinavian Critical Care Trials Group. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014 Oct 9;371(15):1381-91. doi: 10.1056/NEJMoa1406617. Epub 2014 Oct 1. PMID: 25270275. [Free Full Text]
• Mazer CD, Whitlock RP, Fergusson DA, Hall J, Belley-Cote E, Connolly K, Khanykin B, Gregory AJ, de Médicis É, McGuinness S, Royse A, Carrier FM, Young PJ, Villar JC, Grocott HP, Seeberger MD, Fremes S, Lellouche F, Syed S, Byrne K, Bagshaw SM, Hwang NC, Mehta C, Painter TW, Royse C, Verma S, Hare GMT, Cohen A, Thorpe KE, Jüni P, Shehata N; TRICS Investigators and Perioperative Anesthesia Clinical Trials Group. Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery. N Engl J Med. 2017 Nov 30;377(22):2133-2144. doi: 10.1056/NEJMoa1711818. Epub 2017 Nov 12. PMID: 29130845. [Free Full Text]
• National Blood Authority. (2012). Patient Blood Management Guidelines: Module 4 Critical Care. Retrieved January 18, 2023, from https://www.blood.gov.au/system/files/documents/20180424-Module-4.pdf
• National Blood Authority Australia. (2023, January 01). What blood products are supplied – national product price list. Retrieved January 18, 2023, from https://www.blood.gov.au/national-product-price-list
• The Royal Children’s Hospital Melbourne. (n.d.). Ordering Blood Products. Retrieved January 18, 2023, from https://www.rch.org.au/bloodtrans/blood_provision/Ordering_Blood_Products/ Villanueva C, Colomo A, Bosch A, Concepción M, Hernandez-Gea V, Aracil C, Graupera I, Poca M, Alvarez-Urturi C, Gordillo J, Guarner-Argente C, Santaló M, Muñiz E, Guarner C. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013 Jan 3;368(1):11-21. doi: 10.1056/NEJMoa1211801. Erratum in: N Engl J Med. 2013 Jun 13;368(24):2341. PMID: 23281973. [Free Full Text]

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