Patient Blood management

Patient Blood Management is an evidence-based, multidisciplinary approach to optimising the care of patients who might need transfusion. It encompasses measures to avoid transfusion such as anaemia management without transfusion, cell salvage and the use of anti-fibrinolytic drugs to reduce bleeding as well as restrictive transfusion. It ensures that patients receive the optimal treatment, and that avoidable, inappropriate use of blood and blood components is reduced.

Adherence to these principles is measured against NICE quality standard QS138 (2016)

Quality Statement 1: People with iron deficiency anaemia who are having surgery are offered iron supplementation pre operatively

Quality Standard 2: Adults who are having surgery and are expected to have moderate blood loss are offered tranexamic acid

Quality Statement 3: People are clinically reassessed and have their haemoglobin levels checked after each unit of red cells they receive, unless they are bleeding or are on a chronic transfusion programme

Quality Statement 4: People who may need or who have had a transfusion are given verbal and written information about transfusion

Anaemia Management: The diagnosis of anaemia should be based on WHO (2011) classifications (female <120g/l, male <130g/l).

Anaemic patients where MCV/MCH suggests iron deficiency anaemia (MCV <80 +/- MCH <27) should have the cause investigated and treated this may require a gastroenterologist or haematological opinion. Simple haematinic deficiency can be corrected with iron, B12 or Folate replacement as appropriate. Intravenous iron (e.g. Ferinject) can be considered if oral iron is not tolerated or appropriate.

• Surgical technique with meticulous attention to haemostasis should significantly reduce blood loss.

• Correction of acidosis, hypothermia & hypoxia will improve tissue perfusion & coagulation.

• Haemostatic agents: A number of different agents which are applicable in different surgical settings are available.

• Tranexamic acid: Adults who are having surgery and are expected to have moderate blood loss are offered tranexamic acid

• Current medication should be assessed for drugs which increase blood loss & the decision to stop them pre-operatively should be made as appropriate. See also local thrombosis policy.

• Diagnose & treat other co-morbidities: This may reduce the risk of bleeding, help the patient tolerate anaemia better & avoid the need for transfusion.

• Follow Maximum Blood ordering schedule. Due to advances in surgery and the introduction of electronic issue which reduces the time for the lab to prepare blood, few operations require blood ‘on standby’ However to ensure blood is available when required the transfusion requirements in Appendix 1 should be followed

• Intra-operative cell salvage: Currently in the UK, intra-operative cell salvage is considered suitable for patients where estimated blood loss exceeds 1000ml. It should only be undertaken by trained operatives using equipment designed for the purpose of cell collection. Intra-operative cell salvage is only possible in ‘clean’ surgery such as orthopaedics; not in cancer- or bowel-surgery. Departmental Standard operating procedures should be followed

• Patient information: should be given about the possibility of requiring a blood transfusion, &, when appropriate, alternatives to transfusion e.g. intra-operative cell salvage should be discussed.

Erythropoietin is only used rarely in the pre-operative setting (e.g. patients who refuse blood products). It has no routine role in treating anaemia pre-operatively & is associated with an increased thrombotic risk.

Tranexamic Acid is an anti-fibrinolytic agent that has been used for many years in bleeding patients as well as for bleeding prevention. Only recently has more evidence become available leading to the need for a guideline for use for overall & for specific indications.

• Adult trauma patients with, or at risk of, major haemorrhage, in whom antifibrinolytics are not contraindicated, should be given tranexamic acid as soon as possible after injury, at a dose of 1 g intravenously over 10 min followed by a maintenance infusion of 1 g over 8 h (1A). TXA can continue to be given at a dose of 1g QDS (oral/IV) until haemostasis is obtained.

• The use of tranexamic acid should be considered in non-traumatic major bleeding (1B).

• A dose of TXA of 1g QDS can be continued for 48-72 hours post-bleeding episode.

Specific Indications

Obstetric haemorrhage

Early use of tranexamic acid seems to be beneficial in major obstetric haemorrhage.

The WOMAN study Shakur,H. et al (2017) was a large, multi-national, double-blind placebo-controlled trial of tranexamic acid for patients with post-partum haemorrhage. 1g of tranexamic acid (or placebo) was given upon diagnosis of post-partum haemorrhage, with the option of a second dose if bleeding continued after 30 minutes. Death from bleeding was significantly reduced in women given tranexamic acid (1·5% vs 1·9%, RR 0·81, 95% CI 0·65–1·00; p=0·045). The effect was especially marked where tranexamic was given within 3 hours, highlighting the importance of early administration (1·2% vs 1·7%, RR 0·69, 95% CI 0·52–0·91; p=0·008). There was no difference in blood product usage or hysterectomy between the groups. Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group.

Trauma

Adult trauma patients with, or at risk of major haemorrhage, should be given tranexamic acid as soon as possible after injury, at a dose of 1 g intravenously over 10 min followed by a maintenance infusion of 1 g over 8 h (1A).

The utility of antifibrinolytics is clear & subsequent data to CRASH-2 confirms that trauma does indeed induce massive fibrinolytic activation, with the extent relating to the degree of injury Raza,I et al. (2013). NHS England has ensured TA is available to all paramedics at the roadside. For those patients who do not receive TXA pre-admission, there should be no delay in its administration once admitted to hospital. We do not recommend waiting to test for “TEG hyperfibrinolysis” if available, because thromboelastography is an insensitive measure of fibrinolytic activation (Raza et al, 2013).

High-risk patient groups such as cardiac & spinal surgery

In high-risk surgery tranexamic acid at a dose of 10 mg/kg followed by 1 mg/kg/h is recommended to prevent bleeding (1B).

Strong evidence that TXA reduces blood transfusion in surgery has been available for many years Ker, K. et al, (2012); Henry, D.A.,et al (2011). The Horrow regime of 10 mg/kg followed by 1 mg/kg/h (Horrow, J.C. et al 1995), originally devised for use in patients undergoing cardiopulmonary bypass, is the usual regime. Higher doses have no increase in haemostatic effect Kerr, K. et al (2012), & are associated with seizures Kalavrouziotis, D. et al, (2012).

Surgical Patients

NICE Quality standard QS 138 states:

Offer tranexamic acid to adults undergoing surgery who are expected to have at least moderate blood loss (greater than 500 ml).

More recently, the Joint Royal Colleges Tranexamic Acid in Surgery Implementation Group (2022) recommended that tranexamic acid be considered for all patients undergoing inpatient surgery. This was in response to the results of the POISE-3 trial, Devereaux et al.2022) which reported that tranexamic acid reduces major bleeding by 25% and reduces the need for blood transfusion, without increasing the risk of thromboembolic events

This evidence further supports the NICE quality statement on blood transfusion and complements the recent Centre for Perioperative Care guideline ‘Anaemia in the Perioperative Pathway’.

Increasing the use of tranexamic acid in this way may reduce the risk of cancelling elective surgery due to limited availability of blood stocks.

1 gram of TXA should be given by slow intravenous injection at the start and end of surgery. The first dose should be given just prior to skin incision and the last dose given just after skin closure.

TXA is eliminated by renal excretion and there is a risk of accumulation with repeated dosing in patients with renal impairment. However, there would not be a risk of accumulation when giving a single 1g dose just prior to surgery.

Do not routinely use cell salvage without tranexamic acid.

Topic: Transfusion preoperative management Sources checked: Medline, Embase, Cochrane library, TRIP database, NICE, BMJ Best Practice, UpToDate Search terms: preoperative anaemia, preoperative management, maximum blood ordering schedule, tranexamic acid, transfusion Limits: Published since 2018 [not already included in the reference list or reference comments]

Guidelines

Kietaibl, S. et al. (2023) ‘Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care. Second update 2022’, European Journal of Anaesthesiology, 40(4), pp. 226-304. Available at: European Journal of Anaesthesiology (Accessed: 20 September 2023).

National Institute for Health and Care Excellence [NICE] (2020) Perioperative care in adults. NG180. Available at: https://www.nice.org.uk/guidance/ng180 (Accessed: 20 September 2023).

Reports / Summaries

Graetz, T.J., Nuttall, G., Shander, A. (2023) ‘Perioperative blood management: Strategies to minimize transfusions’, in T.W. Post (ed) UpToDate. Waltham, MA: UpToDate. Available at: https://www.uptodate.com/contents/perioperative-blood-management-strategies-to-minimize-transfusions?csi=e91e697a-ef6a-4c29-95e2-e49a9ceb02ea&#x26;source=contentShare (Accessed: 20 September 2023).

Levy, J.H. (2023) ‘Intraoperative use of antifibrinolytic agents’, in T.W. Post (ed) UpToDate. Waltham, MA: UpToDate. Available at: https://www.uptodate.com/contents/intraoperative-use-of-antifibrinolytic-agents?csi=96f946a2-9383-4210-8eb6-3c6ea148d0bc&#x26;source=contentShare (Accessed: 20 September 2023).

[NB. These are time-limited URLs to the full-text. If adding the references to a guideline, use the link https: https://www.uptodate.com/

Reviews

Dai, Z. et al. (2018) ‘The effect of tranexamic acid to reduce blood loss and transfusion on off-pump coronary artery bypass surgery: a systematic review and cumulative meta-analysis’, Journal of Clinical Anesthesia, 44, pp. 23-31. https://dx.doi.org/10.1016/j.jclinane.2017.10.004

Fowler, H. et al. (2022) ‘Impact on blood loss and transfusion rates following administration of tranexamic acid in major oncological abdominal and pelvic surgery: a systematic review and meta-analysis’, Journal of Surgical Oncology, 126(3), pp. 609-621. https://dx.doi.org/10.1002/jso.26900

Fusca, L. et al. (2019) ‘The effectiveness of tranexamic acid at reducing blood loss and transfusion requirement for women undergoing myomectomy: a systematic review and meta-analysis’, Journal of Obstetrics & Gynaecology Canada: JOGC, 41(8), pp. 1185-1192.e1. https://dx.doi.org/10.1016/j.jogc.2018.04.007

Godbey, E.A., Schwartz, J. (2018) ‘Massive transfusion protocols and the use of tranexamic acid’, Current Opinion in Hematology, 25(6), pp. 482-485. https://dx.doi.org/10.1097/MOH.0000000000000457

Houston, B.L. et al. (2020) ‘Efficacy and safety of tranexamic acid in major non-cardiac surgeries at high risk for transfusion: a systematic review and meta-analysis’, Transfusion Medicine Reviews, 34(1), 51-62. https://dx.doi.org/10.1016/j.tmrv.2019.10.001

Kaufner, L. et al. (2020) ‘Erythropoietin plus iron versus control treatment including placebo or iron for preoperative anaemic adults undergoing non‐cardiac surgery’, Cochrane Database of Systematic Reviews, 8, CD012451. Available at: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012451.pub2/full (Accessed: 20 September 2023).

Lu, V.M., Goyal, A., Daniels, D.J. (2019) ‘Tranexamic acid decreases blood transfusion burden in open craniosynostosis surgery without operative compromise’, Journal of Craniofacial Surgery, 30(1), pp. 120-126. https://dx.doi.org/10.1097/SCS.0000000000004875

Ng, O. et al. (2019) ‘Iron therapy for preoperative anaemia’, Cochrane Database of Systematic Reviews, 12, CD011588. Available at: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011588.pub3/full (Accessed: 20 September 2023).

Prasad, S. et al. (2023) ‘Is tranexamic acid associated with decreased need for blood transfusion in percutaneous nephrolithotomy: a systematic review and meta-analysis’, Annals of the Royal College of Surgeons of England, 105(2), pp. 99-106. https://dx.doi.org/10.1308/rcsann.2021.0259

Sun, L., Gao, Q., Feng, Y. (2020) ‘Association of intravenous tranexamic acid and the risk of allogenic blood transfusion in revision hip arthroplasty: a meta-analysis of 4517 patients’, SN Comprehensive Clinical Medicine, 2, pp. 2368–2375. https://doi.org/10.1007/s42399-020-00511-w

Zhang B., He L.-X., Yao Y.-T. (2023) ‘Intravenous tranexamic acid reduces post-operative bleeding and blood transfusion in patients undergoing aortic surgery: a PRISMA-compliant systematic review and meta-analysis’, Reviews in Cardiovascular Medicine, 24(4). Available at: https://www.imrpress.com/journal/RCM/24/4/10.31083/j.rcm2404120 (Accessed: 20 September 2023).

Zhang, Y. et al. (2019) ‘Does tranexamic acid improve bleeding, transfusion, and hemoglobin level in patients undergoing multilevel spine surgery? a systematic review and meta-analysis’, World Neurosurgery, 127, pp. 289-301. https://dx.doi.org/10.1016/j.wneu.2019.02.170

Centre for Perioperative Care (2022) Anaemia in the perioperative pathway. Available at: https://cpoc.org.uk/guidelines-resources-guidelines/anaemia-perioperative-pathway (Accessed: 18 September 2023).

World Health Organisation [WHO] (2011) Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. WHO/NMH/NHD/MNM/11.1. Available at: https://apps.who.int/iris/bitstream/handle/10665/85839/WHO_NMH_NHD_MNM_11.1_eng.pdf (Accessed: 18 September 2023).

Shakur, H. et al. (2017) 'Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial', Lancet, 389(10084), pp. 2105-2116. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446563/ (Accessed: 18 September 2023).

Raza, I. et al. (2013) 'The incidence and magnitude of fibrinolytic activation in trauma patients', Journal of Thrombosis and Haemostasis, 11(2), pp. 307-314. Available at: https://onlinelibrary.wiley.com/doi/full/10.1111/jth.12078 (Accessed: 18 September 2023).

Ker, K. et al. (2012) 'Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis', BMJ, 344, e3054. Available at: https://www.bmj.com/content/344/bmj.e3054 (Accessed: 18 September 2023).

Henry, D.A. et al. 'Anti‐fibrinolytic use for minimising perioperative allogeneic blood transfusion', Cochrane Database of Systematic Reviews, 3, CD001886. Available at: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001886.pub4/full (Accessed: 20 September 2023).

Horrow, J.C. et al. (1995) 'The dose-response relationship of tranexamic acid', Anesthesiology, 82(2), pp. 383-392. Available at: https://pubs.asahq.org/anesthesiology/article/82/2/383/34890/The-Dose-Response-Relationship-of-Tranexamic-Acid (Accessed: 18 September 2023).

Kalavrouziotis, D. et al. (2012) 'High-dose tranexamic acid is an independent predictor of early seizure after cardiopulmonary bypass', Annals of Thoracic Surgery, 93(1), pp. 148-154. Available at:
https://www.annalsthoracicsurgery.org/article/S0003-4975(11)01913-8/fulltext (Accessed: 20

The UK Royal Colleges Tranexamic Acid Surgery Implementation Group (2022) 'Tranexamic acid for safer surgery: the time is now', British Journal of Surgery, 109(12), pp. 1182-1183. Available at: https://academic.oup.com/bjs/article/109/12/1182/6678119?login=true (Accessed: 20 September 2023).September 2023).

Devereaux, P.J. et al. (2022) 'Tranexamic acid in patients undergoing noncardiac surgery', New England Journal of Medicine, 386(21), pp. 1986-1997. Available at: https://www.nejm.org/doi/10.1056/NEJMoa2201171 (Accessed: 20 September 2023).

This guideline has been registered with the trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date. This guideline is for use in Frimley Health Trust hospitals only. Any use outside this location will not be supported by the Trust and will be at the risk of the individual using it.

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