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Blood transfusion
Transfusions of blood and blood products
The transfusion of blood products is often a lifesaving and highly valuable process. It is also expensive and potentially dangerous, and the level of knowledge of health care workers of the risks of transfusion is not always ideal.
The majority of medical patients who are anaemic do not require transfusion. Clearly, patients with active bleeding and haemodynamic compromise do, and there is a grading of indications from that extreme to the mildly tired but undistressed patient with an anaemia of chronic disorder, where treating the underlying cause is a more elegant (and cheaper and safer) solution. Startling, a couple of observational studies from the US reached remarkably similar estimates of the proportion of unnecessary transfusions (40 to 50%.)1,2 This figure is a stark reminder of how lack of in-house audit of transfusion practices, and lack of clear guidance on transfusion indications, may lead to inappropriate use.
Issues with transfusing stable anaemic medical patients
Slowly developing anaemia such as that due to chronic iron or B12 deficiency results in compensatory mechanisms coming into play. Tissue hypoxia due to anaemia leads to raised erythropoeitin levels, but if this does not result in a haemoglobin concentration rise, then vasodilatation remains as the main response, vasodilatation drops BP and renal perfusion and leads to increased salt and water retention to fill the increased intravascular space.3 This manifests as the common findings in anaemic patients of a bounding pulse (wide pulse pressure from the vasodilatation) and peripheral oedema. The clinical consequence is a reduced ability to handle a sudden intravenous fluid load, as capacitance vessels are already in use, meaning that giving saline to anaemic patients may result in the prompt appearance of pulmonary oedema, and similarly, large packed cell infusions may be poorly tolerated.
Transfusion thresholds
Transfusion thresholds have only been established for a number of conditions, but it may be reasonable to extrapolate to other similar situations. For instance in a Spanish study of 921 patients with upper GIT bleeding, no melaena, and presenting at a facility where endoscopy was performed within 6 hours, and bleeding if found was addressed appropriately, there was no advantage to a more restrictive transfusion threshold (Hb < 7) over a more liberal one (transfuse if Hb < 9.)4 The restrictive strategy was associated, unsurprisingly, with fewer transfusion reactions (mean amount of blood transfused 1.2 litres per patient less) but more disconcertingly and perhaps just reflecting the smallish sample size, with a significantly lower overall mortality (5% vs 9%, NNT 25, 95% CI 14 to 185.)
The MINT trial compared a more liberal transfusion threshold (allowing transfusion if Hb < 10 g/dL) with a restrictive one (only transfuse if Hb< 7 g/dL) in 3504 patients who has sustained a myocardial infarction. There was an approximately 2% difference in both mortality (9.9% vs 8.3%) and in the primary combined endpoint of death or new myocardial infarction (16.9% vs 14.5%) but neither of these reached statistical significance after adjusting for incomplete follow-up. Patients in the liberal transfusion arm received an average of 1.8 more units of packed cells (0.7 vs 2.5.)5
Transfusion thresholds (in the absence of active bleeding) of 7 g/100ml are probably safe across a range of surgical and medical conditions.6
Single unit transfusions
One practical way of dealing with both unexpected pulmonary oedema and the difficulty in defining exact transfusion thresholds in medical patients is to opt for a strategy of single unit transfusions, with an assessment of the benefit of further transfusion, after each unit.7
TRALI
TRALI (transfusion associated acute lung injury) is the third commonest cause of transfusion related death in some older series.8 (ABO related haemolysis accounted for half, infection for 10%) and is characterised by dyspnoea, hypotension, pulmonary oedema and fever developing within 4 hours of a transfusion. Milder cases may just be dyspnoeic and hypoxaemic on pulse oximetry without pulmonary oedema on CXR. It is often not considered by clinicians.9 The disease may be due to HLA antibodies and antibodies against leukocytes present in donor plasma, and is fatal in up to 10% of patients. Nearly three quarters of patients will need ventilation, although usually only for a few days, and management is supportive.
Soril LJJ, Noseworthy TW, Stelfox HT, Zygun DA, Clement FM. A retrospective observational analysis of red blood cell transfusion practices in stable, non-bleeding adult patients admitted to nine medical-surgical intensive care units. J Intensive Care. 2019 Apr 4;7:19. doi: 10.1186/s40560-019-0375-3. PMID: 30988954; PMCID: PMC6449900 ↩
Jadwin DF, Fenderson PG, Friedman MT, Jenkins I, Shander A, Waters JH, Friedman A, Tesoriero E, Refaai MA, Shih AW, Awan T, Ngo AL, Perez JA, Reynolds JD. Determination of Unnecessary Blood Transfusion by Comprehensive 15-Hospital Record Review. Jt Comm J Qual Patient Saf. 2023 Jan;49(1):42-52. doi: 10.1016/j.jcjq.2022.10.006. Epub 2022 Nov 8. PMID: 36494267 ↩
Anand IS, Chandrashekhar Y, Ferrari R, Poole-Wilson PA, Harris PC. Pathogenesis of oedema in chronic severe anaemia: studies of body water and sodium, renal function, haemodynamic variables, and plasma hormones. Br Heart J. 1993 Oct;70(4):357-62. doi: 10.1136/hrt.70.4.357. PMID: 8217445; PMCID: PMC1025332. ↩
Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding N Engl J Med 2013;368:11-21 ↩
Carson JL, Brooks MM, Hébert PC, et al; MINT Investigators. Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia. N Engl J Med. 2023 Nov 11. doi: 10.1056/NEJMoa2307983. Epub ahead of print. PMID: 37952133. ↩
Carson JL, Stanworth SJ, Dennis JA, Trivella M, Roubinian N, Fergusson DA, Triulzi D, Dorée C, Hébert PC. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database of Systematic Reviews 2021, Issue 12. Art. No.: CD002042. DOI: 10.1002/14651858.CD002042.pub5. Accessed 03 February 2023 ↩
Yang WW, Thakkar RN, Gehrie EA, Chen W, Frank SM. Single-unit transfusions and hemoglobin trigger: relative impact on red cell utilization. Transfusion. 2017 May;57(5):1163-1170. doi: 10.1111/trf.14000. Epub 2017 Feb 5. PMID: 28164305. ↩
Sazama K. Reports of 355 transfusion associated deaths: 1976 through 1985. Transfusion. 1990;30:583-90 ↩
Kopko PM, Marshall CS, MacKenzie MR. Transfusion related acute lung injury. Report of a clinical look-back investigation. JAMA. 2002;287:1968-71 ↩