Management of severe peri-operative bleeding

Peri-operative blood loss1–3 and also the transfusion of red blood cell (RBC),1,2,4 plasma,5 and platelets6 are associated with adverse outcomes1,2,7 and high costs.8 Although, in a considerable percentage of individual surgical procedures it is the surgical technique itself that results in the increased surgical blood loss, anaesthesiologists are generally required to solve the problem. The European Society of Anaesthesiology and Intensive Care (ESAIC) therefore has created guidelines on the management of severe peri-operative bleeding, the first being published in 2013.9 In this issue of the Journal, Kietaibl et al.10 publish the second update of these guidelines. These updated guidelines are elaborate and contain all you ever wanted to know about peri-operative bleeding management. We all are grateful for our Society's vision to decide to update these guidelines in 2020 and for the authors’ hard work during the last 2.5 years. The recommendations cover 13 clinical fields and are presented in the form of 16 recommendations each comprising between 3 and 27 graded sub-recommendations – a total of 193! The invitation to write an editorial to accompany these guidelines is, of course, a great honour! However, commenting on such comprehensive work by the European experts is quite challenging! Since it would be rather arrogant to comment on such tremendous work systematically, we opted to comment on a few points that we considered were worthy of note. This is deliberately unsystematic and does not claim completeness. The best strategy in coagulation management is to prevent peri-operative bleeding. Such preventive action starts during the pre-anaesthesia consultation with a drug and bleeding history. It is important to identify patients with an increased peri-operative bleeding risk (e.g., due to underlying coagulation disorders, or anticoagulant or platelet inhibitor drugs) so that appropriate preventive measures can be instituted pre-operatively. Conventional coagulation tests (e.g., prothrombin time, activated prothrombin time, etc.) are not reliable predictors of the peri-operative bleeding risk, and normal results give the physician a false sense of security.11 Although still regularly performed, routine coagulation tests are therefore not recommended. Instead, a standardised coagulation questionnaire is more powerful to detect an underlying coagulation disorder if it is suspected clinically.12,13 Which patients should be optimised, and how, before surgery? Pre-operative anaemia detection and treatment is recommended (Recommendation 1): of course, this is of outmost importance. However, it is suggested that parenteral pre-operative treatment would correct anaemia within 1–2 weeks (grade 2C). In our experience, this is a rather optimistic expectation. Recent studies show that treatment of iron deficiency anaemia prior to cardiac surgery using intravenous iron with14 or without15 erythropoiesis stimulating agents increase the haemoglobin by 12 g l−1 and 8 g l−1, and this was after these treatments were given for 30 days before surgery. Interestingly, transfusion needs were reduced by the combined treatment14 as shown in ultra-short term treatment.16 Nevertheless, the exact contribution of type and dose of erythropoiesis stimulating agents, intravenous iron, subcutaneous vitamin B12 and oral folic acid and the timing of such stimulation is still unclear today. Patients undergoing obstetric surgery (Recommendation 12): the ESAIC guidelines suggest that ‘dynamic platelet count decrease or a level <150 × 10−9 l−1 at the onset of labour, particularly if combined with plasma fibrinogen level <2.0 g l−1, may indicate an increased risk of postpartum haemorrhage (grade C)’.10 However, in a prospective cohort study of 1300 women, prepartum factor XIII activity had the strongest correlation with postpartum blood loss.17 Therefore, additionally measuring prepartum factor XIII levels may help in anticipating an increased risk of postpartum haemorrhage. Whether factor XIII replacement reduces postpartum haemorrhage needs to be evaluated in future studies. Use of recombinant factor VIIa in postpartum haemorrhage (Recommendation 12): we strongly agree with the recommendation against the prophylactic/general use of recombinant factor VIIa in postpartum haemorrhage (grade 1C). Nevertheless, classifying all use of recombinant factor VIIa in postpartum haemorrhage as off-label is not entirely correct. Recombinant factor VIIa has been approved by the European Medical Agency in 2022 to ‘treat patients with severe postpartum haemorrhage, when medicines that stimulate the muscles of the womb to contract (uterotonic medicines) are not effective at controlling the bleeding’.18 The future will show the best indication of recombinant factor VIIa in severe postpartum haemorrhage. Direct oral anticoagulants (DOACs) (Recommendation 2): the ESAIC guidelines suggest that ‘in severe bleeding patients treated with dabigatran, a specific antidote (idarucizumab) could be considered (2C)’ and ‘the use of prothrombin complex concentrate (25 IU kg−1 at first) over andexanet alfa in bleeding patients treated with anti-Xa agents (rivaroxaban, apixaban, edoxaban) (2C)’. In bleeding patients, the first measure is to assess whether they are anticoagulated, with which anticoagulant and to quantify the residual DOAC plasma concentration. This information can be achieved with anti-Xa activity for anti-Xa inhibitors, prothrombin time for vitamin K antagonists and (diluted) thrombin time for dabigatran.19 In an ongoing and life-threatening bleeding case, DOAC reversal is indicated only if there is a relevant residual plasma concentration. For reversal of anti-Xa inhibitors the choice between prothrombin complex concentrate (PCC) and andexanet alfa is difficult at the present time due to very limited scientific evidence. A recent propensity score-matched analysis showed that the adjusted 30-day mortality rates were lower for patients treated with andexanet alfa than in matched patients receiving PCC.20 Further studies comparing these two drugs on different outcomes are necessary to reach a final conclusion. The recommendation regarding the use of idarucizumab for dabigatran reversal in an ongoing haemorrhage is surprisingly restrained. Alternatives to idarucizumab are lacking and PCC has been shown to be ineffective for dabigatran reversal.21 Moreover, an underlying coagulopathy can be only detected and appropriately treated after the dabigatran effect has been neutralised.22 The only clinical field that is not covered by the guidelines is trauma. This was a deliberate choice by the authors and may be due to the fact that there have been European guidelines on the management of major bleeding and coagulopathy following trauma since 2007. The update of the current version number 519 will be published in the first months of 2023. These guidelines cover all the aspects of trauma treatment from the prehospital period to the treatment in the emergency room, surgical and interventional procedures and intensive care management.19 With all the amount of information in the ESAIC guidelines on the management of severe peri-operative bleeding, we might expect all problems to be solved. Unfortunately, this is not the case. Which physician can find the one sub-recommendation out of nearly 200 that is pertinent for the sudden problem encountered at 2 AM in complex emergency surgery? None. Therefore, within anaesthesia departments this information needs to be taught, and easy to follow algorithms established (Table 1). Algorithms that guide the pre-operative optimisation of patients undergoing high (>500 ml) blood loss surgery who have anaemia and iron deficiency,23 algorithms that guide the pre-operative cessation of anticoagulants without bridging, and algorithms that guide the pre-operative cessation of or continuation of antiplatelet treatment. In addition, we need an algorithm that guides intra-operative coagulation management. This algorithm needs to include the necessary coagulation monitoring including traditional laboratory data and viscoelastic tests to find out whether there is a coagulation issue and, if so, what needs to be done to correct the coagulation situation in an individualised goal-directed manner. The success of such coagulation algorithms has been shown in trauma,24 cardiac surgery,25 liver transplantation,26 and burns.27 Such algorithms are strongly recommended by the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists28 and the European Society of Cardiology, endorsed by the ESAIC.29 Table 1 - Anaesthesia departments should provide algorithms for Pre-operative anaemia detection and treatment Peri-operative management of patients with anticoagulant and/or antiplatelet treatment Peri-operative bleeding management Postpartum haemorrhage Patients under anticoagulant therapy with intracranial haemorrhage Such algorithms are not freely floating in the medical universe but are, as stated by the authors, part of patient blood management (PBM). PBM has been taken up by the World Health Organization (WHO) and documented by the publication of their Policy Brief on October 19, 202130 in which they call on their 194 member states to action and announce the upcoming WHO initiative to develop PBM implementation guidelines directed towards healthcare leaders of all member states. By this unprecedented campaign the WHO sets standards. PBM has become the new standard. Likewise, the above-described algorithms have become standard. Thus, implementation is mandatory – nobody wants to deliver substandard care.