6. Single unit Transfusion

Why single-unit RBC transfusion

For RBC transfusion, single-unit dosing has been proven safe when applied together with a restrictive transfusion trigger (pre-transfusion haemoglobin level or symptoms of anaemia) in a number of randomized controlled trials (RCTs). Transfusion of one unit should be followed by a clinical or laboratory assessment of the patient to review if transfusion therapy is adequate or more units are needed.

Transfusion of two or more RBC units in succession is associated with an increased risk of pulmonary oedema or transfusion-associated circulatory overload (TACO), especially in the elderly, females and patients with heart or kidney failure, or a positive fluid balance.

A single unit of RBC will often relieve acute symptoms of anaemia and/or raise haemoglobin level in a stable patient to a level above the guideline trigger, in which case transfusion may be unnecessary according to the guideline, or can be postponed or replaced by other anaemia treatment. If one unit of RBC is given to an anaemic and otherwise stable patient, this is a single-unit transfusion provided that no further units are given until seeing a post-transfusion haemoglobin, or stating a new clinical transfusion indication, or within 24 hours after transfusing the first RBC unit. RBC transfusion is inappropriate therapy for iron deficiency anaemia unless there is acute bleeding or symptoms of acute physiological stress due to compromised oxygen delivery (for more information on anaemia diagnosis and treatment, please visit the Pre-operative Anaemia page).

For patients who are chronically transfused with RBC, there are no randomized studies to guide threshold or dosing scheme. Transfusion treatment should be tailored individually, based on a clinical decision and the patient’s response to previous transfusions.

Platelets and plasma single-unit transfusion

The principle of avoiding over-transfusion through routinely ordering more than one unit in the non-bleeding patient also applies to platelets and plasma. However there is limited evidence to support a fixed number of units, as platelets and coagulation factors may be removed or consumed in various non-bleeding clinical conditions, e.g. in the presence of platelet antibodies, sepsis or disseminated intravascular coagulation.

Platelet transfusion should be guided by the clinical indication, platelet count and functional platelet tests, as recommended by guidelines for specific patient populations.
Plasma transfusion should be guided by clinical indication and pre- and post-transfusion coagulation tests and/or point-of-care whole blood functional assays according to evidence and guidelines for the specific patient population.

Summary of evidence base

Single-unit RBC transfusion was standard care in the majority of RCTs comparing liberal to restrictive transfusion in circulatory stable patients with anaemia [1-6]. These studies form the evidence base for RBC transfusion in these patient populations, and therefore when translating these findings into daily practice, both haemoglobin trigger and RBC dose should be followed.

Moreover, some of the RCT studies [2,3] and meta-analysis of RCT data [7] have shown that even with a single-unit dose, liberal transfusion is still associated with higher frequency of pulmonary oedema or TACO, compared with the restrictive regime. This indicates that either the higher number of units transfused to patients in the liberal arm or the higher haemoglobin level reached in this way increases the risk for TACO.

Finally, observational studies have found that the risk of TACO increases with every RBC unit transfused [8], that passive reporting greatly underestimates the frequency of TACO [10,11], and that TACO may increase morbidity and mortality. Accordingly the introduction of a single-unit regime is generally encouraged to avoid TACO, and in patients with cancer or haematological malignancy a single-unit regime has not been associated with adverse effects (non-randomized studies) [12,13]. Transfusion therapy in severely bleeding patients should follow separate guidelines/evidence for this patient population [14-16].

Practical tools to support implementation

Clinical assessment of the patient’s haemoglobin after transfusion of a single-unit is recommended to guide the evidence-based transfusion treatment of RBC [21]. Education, engagement and training may lead to an increase in single-unit transfusion, as may computerized physician order entry (CPOE) and/or regular audits. All of these have proven effective in some institutions but not in others, and no specific single type of intervention has proven superior in all settings.

Supplementary information

A dose of 4 ml red cells/kg raises haemoglobin concentration by 10g/L, which corresponds to the increment of one unit of red cells in a 70 kg patient.
One adult therapeutic dose of platelets (from a pool of four units derived from whole blood donations or single-donor apheresis) typically raises the platelet count by 20-40x10⁹/L.
The typical dose of fresh frozen plasma is 12-15 ml/kg [Reference].

Key audit criteria

Audit (whether electronic or manual) should clearly define the patient population.
The target population audited should correspond to the target population of the guideline (for a GRADE-based guideline, this corresponds to the patient population of each “PICO-question” leading the comparison).
Diagnoses and surgical procedures should be registered.
Patients with bleeding emergencies (or massive transfusion) should be excluded.
The Joint Commission has proposed a definition of patient populations for the purpose of performance measurement [22].
The audit will often address both pre-transfusion trigger as well as single-unit transfusion, as the single-unit transfusion is the dosage for each transfusion trigger.

References

1. Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG, Nemo G, Dragert K, Beaupre L, Hildebrand K, Macaulay W, Lewis C, Cook DR, Dobbin G, Zakriya KJ, Apple FS, Horney RA, Magaziner J: Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med 2011;365:2453-2462.
2. Villanueva C, Colomo A, Bosch A, Concepcion M, Hernandez-Gea V, Aracil C, Graupera I, Poca M, varez-Urturi C, Gordillo J, Guarner-Argente C, Santalo M, Muniz E, Guarner C: Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013;368:11-21.
3. Hébert PC: Transfusion requirements in critical care (TRICC): a multicentre, randomized, controlled clinical study. Transfusion Requirements in Critical Care Investigators and the Canadian Critical care Trials Group. Br J Anaesth 1998;81 Suppl 1:25-33.
4. Lacroix J, Hebert PC, Hutchison JS, Hume HA, Tucci M, Ducruet T, Gauvin F, Collet JP, Toledano BJ, Robillard P, Joffe A, Biarent D, Meert K, Peters MJ: Transfusion strategies for patients in pediatric intensive care units. N Engl J Med 2007;356:1609-1619.
5. Hajjar LA, Vincent JL, Galas FR, Nakamura RE, Silva CM, Santos MH, Fukushima J, Kalil FR, Sierra DB, Lopes NH, Mauad T, Roquim AC, Sundin MR, Leao WC, Almeida JP, Pomerantzeff PM, Dallan LO, Jatene FB, Stolf NA, Auler JO, Jr.: Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA 2010;304:1559-1567.
6. Holst LB, Haase N, Wetterslev J, Wernerman J, Aneman A, Guttormsen AB, Johansson PI, Karlsson S, Klemenzson G, Winding R, Nebrich L, Albeck C, Vang ML, Bulow HH, Elkjaer JM, Nielsen JS, Kirkegaard P, Nibro H, Lindhardt A, Strange D, Thormar K, Poulsen LM, Berezowicz P, Badstolokken PM, Strand K, Cronhjort M, Haunstrup E, Rian O, Oldner A, Bendtsen A, Iversen S, Langva JA, Johansen RB, Nielsen N, Pettila V, Reinikainen M, Keld D, Leivdal S, Breider JM, Tjader I, Reiter N, Gottrup U, White J, Wiis J, Andersen LH, Steensen M, Perner A: Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial. Trials 2013;14:150.
7. Salpeter SR, Buckley JS, Chatterjee S: Impact of more restrictive blood transfusion strategies on clinical outcomes: a meta-analysis and systematic review. Am J Med 2014;127:124-131.
8. Menis M, Anderson SA, Forshee RA, McKean S, Johnson C, Holness L, Warnock R, Gondalia R, Worrall CM, Kelman JA, Ball R, Izurieta HS: Transfusion-associated circulatory overload (TACO) and potential risk factors among the inpatient US elderly as recorded in Medicare administrative databases during 2011. Vox Sang 2014;106:144-152.
9. Murphy EL, Kwaan N, Looney MR, Gajic O, Hubmayr RD, Gropper MA, Koenigsberg M, Wilson G, Matthay M, Bacchetti P, Toy P: Risk factors and outcomes in transfusion-associated circulatory overload. Am J Med 2013;126:357-38.
10. Raval JS, Mazepa MA, Russell SL, Immel CC, Whinna HC, Park YA: Passive reporting greatly underestimates the rate of transfusion-associated circulatory overload after platelet transfusion. Vox Sang 2015; 108 (4): 387–392.
11. Narick C, Triulzi DJ, Yazer MH: Transfusion-associated circulatory overload after plasma transfusion. Transfusion 2012;52:160-165.
12. Berger MD, Gerber B, Arn K, Senn O, Schanz U, Stussi G: 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 2012;97:116-122.
13. Boone JD, Kim KH, Marques M, Straughn JM: Compliance rates and outcomes associated with a restrictive transfusion policy in gynecologic oncology patients. Gynecol Oncol 2014;132:227-230.
http://www.gynecologiconcology-online.net/article/S0090-8258(13)01268-7/abstract
14. National Blood Authority of Australia: Patient Blood Management Guidelines; 2013.
15. McQuilten ZK, Crighton G, Engelbrecht S, Gotmaker R, Brunskill SJ, Murphy MF, Wood EM: Transfusion Interventions in Critical Bleeding Requiring Massive Transfusion: A Systematic Review. Transfus Med Rev 2015; 29 (2):127–137.
16. Sundhedsstyrelsen: National Klinisk Retningslinje om indikation for transfusion med blodkomponenter. 2018
17. National Blood Authorities of Australia, http:, www.blood.gov.au/pbm-guidelines: Patient Blood Management Guideline; 2013.
18. Carson JL, Grossman BJ, Kleinman S, Tinmouth AT, Marques MB, Fung MK, Holcomb JB, Illoh O, Kaplan LJ, Katz LM, Rao SV, Roback JD, Shander A, Tobian AA, Weinstein R, Swinton McLaughlin LG, Djulbegovic B: Red blood cell transfusion: a clinical practice guideline from the AABB*. Ann Intern Med 2012;157:49-58.
19. Retter A, Wyncoll D, Pearse R, Carson D, McKechnie S, Stanworth S, Allard S, Thomas D, Walsh T: Guidelines on the management of anaemia and red cell transfusion in adult critically ill patients. Br J Haematol 2013;160:445-464.
20. Alam A, Lin Y, Lima A, Hansen M, Callum JL: The prevention of transfusion-associated circulatory overload. Transfus Med Rev 2013;27:105-112.
21. Murphy MF, Waters JH, Wood EM, Yazer MH: Transfusing blood safely and appropriately. BMJ 2013;347:f4303.
22. Gammon HM, Waters JH, Watt A, Loeb JM, Donini-Lenhoff A: Developing performance measures for patient blood management. Transfusion 2011;51:2500-2509.

Relevant guidelines

Australian National Blood Authority (NBA) - Patient Blood Management [17,18] (GRADE-equivalent methodology)
The management of anaemia and red cell transfusion in adult critically ill patients (GRADE-based) [19]
Carson et al. AABB [18] (based on a Cochrane-review)
Danish Health and Medicines Authority [16] (GRADE-based in Danish; expected as an English publication in the course of 2015)
The Prevention of Transfusion-Associated Circulatory Overload [20]