19TH AN NUAL S Y M P O S I U M ON PATIENT BLOOD MANAGEMENT, HAEMOSTASIS AND THROMBOSIS Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis ABSTRACT BOOK Abstracts of the 19th Annual NATA Symposium on Patient Blood Management, Haemostasis and Thrombosis April 12‒13, 2018 Lisbon, Portugal SPEAKER ABSTRACTS Preoperative Anaemia ‒ Is Iron the Best Answer? 3 Treatment of Anaemia 6 Weighing the Evidence for Coagulation Therapies in Cardiac Surgery 9 (Session organised in collaboration with the European Association of Cardiothoracic Anaesthesiology) Transfusions – The Second Best Option? 12 Patient Blood Management ‒ Improved Standards of Care, Patient Safety and Cost-Effectiveness 14 Fluid Therapy 17 The Newest Evidence 20 Patient Blood Management for Specific Indications 22 All Aboard – Patient Blood Management Multidisciplinary Implementation 27 (Session organised in collaboration with Anemia Working Group Portugal) How to Treat Coagulopathy 31 POSTER ABSTRACTS Blood Transfusion Services/Risks of Transfusion 34 Transfusion Practice 42 Blood Conservation Strategies/Autologous Transfusion 64 Anaemia Effects and Management 78 Fluid Therapy/Oxygen Carriers 117 Haemostasis and Thrombosis 118 Disclaimer This abstract book has been produced using author-supplied copy. Editing has been restricted to some corrections of spelling and style where appropriate. No responsibility is assumed for any claims, instructions, methods or drug dosages contained in the abstracts; it is recommended that these are verified independently. 2 Abstracts of the 19th Annual NATA Symposium Speaker Abstracts Abstracts of the 19th Annual NATA Symposium on Patient Blood Management, Haemostasis and Thrombosis Speaker Abstracts Preoperative Anaemia ‒ Is Iron the Best Answer? S1 What is the best way to classify anaemia? J. Keidan Consultant Haematologist (retired), UK Anaemia is identified on the basis of a simple blood count, when the haemoglobin concentration is below the “normal” range for age and sex. However, anaemia is not a diagnosis of itself and is traditionally classified on the basis of underlying cause. The causes of anaemia, both congenital and acquired, will be presented to provide a theoretical background to investigating a patient found to have a low haemoglobin. However, this “classical” approach to diagnosis of anaemia can be unrealistic outside the setting of a formal haematology clinic. I will therefore provide a more pragmatic approach to investigating anaemia, with emphasis on preoperative workup. 3 Abstracts of the 19th Annual NATA Symposium Speaker Abstracts S2 Management of preoperative iron deficiency – current evidence A. Klein Consultant Anaesthetist, Royal Papworth Hospital, Cambridge, UK; Editor-in-Chief, Anaesthesia This talk will discuss anaemia in the context of preoperative optimisation before surgery and discuss the scale of the problem. Up to 40% of patients presenting for surgery may be anaemic, and this is increasingly common as patients are getting older and sicker. We are facing an epidemic of anaemia, but, in many centres, patients are not investigated nor treated. There is marked regional variation in both anaemia and transfusion, with a consistently high incidence of both. Perioperative anaemia, blood loss and allogeneic blood transfusion are associated with increased postoperative morbidity and mortality, and prolonged hospital stay. A multidisciplinary, multimodal, individualised strategy, collectively termed ‘patient blood management’, may reduce or eliminate allogeneic blood transfusion and improve outcomes. This approach has three objectives: the detection and treatment of perioperative anaemia; the reduction of perioperative bleeding and coagulopathy; and harnessing and optimising the physiological tolerance of anaemia. There are numerous causes of anaemia in surgical patients, the most common is iron deficiency or iron restriction. Preoperative anaemia is associated with increased mortality and worse outcomes, including increased transfusion and complications. Anaemia should be detected before surgery that is likely to cause significant blood loss, preferably at least 30 days before scheduled operations. The cause of preoperative anaemia should be identified and treated if possible. Bleeding from the GI tract and the genito-urinary system should be considered and investigated. Major surgery may have to be rescheduled, whereas minor procedures, without blood loss, can proceed in parallel with the evaluation of anaemia Different treatment options will be discussed and compared in both elective and urgent surgery. Optimising patients with anaemia before surgery may reduce allogeneic transfusion and improve outcomes as part of a comprehensive blood management programme, and this forms a vital part of perioperative patient care. REFERENCES 1. Klein AA, Collier T, and the Association of Cardiothoracic Anaesthetists (ACTA). The incidence and importance of anaemia in patients undergoing cardiac surgery in the UK – the first ACTA national audit. Anaesthesia 2016; 71: 627-35 2. Musallam KM, Tamim HM, Richards T, et al. Preoperative anaemia and postoperative outcomes in non-cardiac surgery: a retrospective cohort study. Lancet 2011; 378: 1396-407 3. Clevenger B, Richards T. Pre-operative anaemia. Anaesthesia 2015; 70 Suppl 1: 20-8 4. Partridge J, Harari D, Gossage J, Dhesi, J. Anaemia in the older surgical patient: A review of prevalence, causes, implications and management. J R Soc Med 2013; 106: 269-77 5. Hung M, Ortmann E, Besser M, et al. A prospective observational cohort study to identify the causes of anaemia and association with outcome in cardiac surgical patient. Heart 2015; 101: 107-12 6. Clevenger B, Mallett SV, Klein AA, Richards Y. Patient blood management to reduce surgical risk. BMJ 2015; 102: 1325- 37 7. Litton E, Xiao J, Ho KM. Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials. BMJ 2013; 347: f4822 4 Abstracts of the 19th Annual NATA Symposium Speaker Abstracts S3 Comparative safety of intravenous iron formulations M. Auerbach Auerbach Hematology and Oncology, Baltimore, MD, and Georgetown University School of Medicine, Washington, DC, USA Oral iron has been used to treat iron deficiency since Syndenham first used iron filings in cold wine to treat chlorosis.1 Oral iron causes significant gastrointestinal perturbation in more than 70% of those to whom it is prescribed.2 New data suggest oral iron increases hepcidin decreasing subsequent absorption for 48-72 hours.3 The earliest intravenous formulations were associated with severe infusion reactions due to the release of large amounts of labile free iron.4,5 Iron sucrose and ferric gluconate are safe and effective but larger amounts of labile free iron mitigate large replacement doses in a single setting. Newer formulations which bind elemental iron more tightly slowing release of labile free iron are able to be administered as 1000 mg in 15-60 minutes. Misconceptions of the nature and incidence of serious adverse events are due to earlier formulations of high molecular weight iron dextran, which are no longer available.6 Inappropriate intervention for minor infusion reactions with antihistamines and vasopressors can convert a self-limited reaction which resolves without treatment into a haemodynamically significant serious adverse event.7 Prospective, observational and intra-institutional retrospective studies support equivalent safety and efficacy among the available intravenous iron formulations.7 A high-quality meta-analysis comprising more than 10,000 patients who received intravenous iron compared to placebo, oral iron and intramuscular iron concluded that while minor infusion reactions are observed there was no increment in serious adverse events compared to any of the comparators.8 Intravenous iron is the preferred route of administration after oral iron intolerance and has been shown to be safe in pregnancy,9 bariatric surgery,10 inflammatory bowel disease,11 in the perioperative period12 and a host of other conditions associated with iron lack. Complete replacement dosing of intravenous iron in one to two short sessions is underutilised. REFERENCES 1. Blaud P. Sur les maladies chloropiques et sur un mode de traitement spécifique dans ces affections. Rev Med Fr Etrang 1832; 45: 357-67 2. Tolkien Z, Stecher L, Mander AP, Pereira DI, Powell JJ. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One 2015; 10: e0117383 3. Stoffel NU, Cercamondi CI, Brittenham G, et al. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol 2017; 4: e524-e33 4. Auerbach M, Ballard H. Clinical use of intravenous iron: administration, efficacy, and safety. Hematology Am Soc Hematol Educ Program 2010; 2010: 338-47 5. Jahn MR, Andreasen HB, Futterer S, et al. A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications. Eur J Pharm Biopharm 2011; 78: 480-91 6. Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmén J. Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant 2006; 21: 378-82 7. Auerbach M, Deloughery T. Single-dose intravenous iron for iron deficiency: a new paradigm. Hematology Am Soc Hematol Educ Program 2016; 2016: 57-66 8. Avni T, Bieber A, Grossman A, Green H, Leibovici L, Gafter-Gvili A. The safety of intravenous iron preparations: systematic review and meta-analysis. Mayo Clin Proc 2015; 90: 12-23 9. Breymann C, Auerbach M. Iron deficiency in gynecology and obstetrics: clinical implications and management. Hematology Am Soc Hematol Educ Program 2017; 2017: 152-9 10. Malone M. Recommended nutritional supplements for bariatric surgery patients. Ann Pharmacother 2008; 42: 1851-8 11. Kulnigg S, Stoinov S, Simanenkov V, et al. A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial. Am J Gastroenterol 2008; 103: 1182-92 12. Laso-Morales M, Jericó C, Gómez-Ramírez S, et al. Preoperative management of colorectal cancer-induced iron deficiency anemia in clinical practice: data from a large observational cohort. Transfusion 2017; 57: 3040-8 5 Abstracts of the 19th Annual NATA Symposium Speaker Abstracts Treatment of Anaemia S4 Anaemia in the elderly ‒ something special? D. Girelli Department of Medicine, Section of Internal Medicine, University of Verona; Veneto Region Referral Center for Iron Metabolism Disorders; Center of Excellence for Rare Hematological Diseases “EuroBloodNet”; Policlinico Giambattista Rossi, Verona, Italy Anaemia affects up to forty percent of the elderly population, representing a public health problem that is predicted to further increase in coming years because of the demographic drive. Being typically mild, it is quite often falsely perceived as a minor problem, particularly in the elderly with multimorbidity, resulting in under-investigation of the causes, as well as under-treatment. Nonetheless, a bulk of evidence indicates that anaemia in the elderly is independently associated with disability and other major negative outcomes, including an increased mortality risk. Anaemia in the elderly is generally multifactorial, but initial studies suggested that aetiology remain unexplained in nearly one-third of cases. This high proportion is consistently declining due to recent advances highlighting the role of several conditions including clonal haematopoiesis, “inflammaging”, correctable androgen deficiency in men, and under-recognised iron deficiency. Starting from a real-world case vignette illustrating a paradigmatic example of anaemia in an elderly patient with multimorbidity, I will review current knowledge on definition, epidemiology, clinical, and pathophysiological aspects of anaemia in the elderly, giving some practical insights on how to manage similar cases. 6 Abstracts of the 19th Annual NATA Symposium Speaker Abstracts S5 Iron deficiency – it’s not just anaemia T. Richards Division of Surgery and Interventional Science, University College London, London, UK Iron is vital not just for haemoglobin but for many aspects of cellular function. Whilst blood collects oxygen from the lungs and delivers it to the tissues, it is the utilisation of oxygen through aerobic metabolism to produce energy that is perhaps the most important role for iron. Oxygen is processed by cytochromes in the electron transport chain of the mitochondria to produce ATP. Iron is the key component of the cytochrome and its ability to flip between ferrous and ferric states mediates the metabolism of oxygen. In iron deficiency, whilst the haemoglobin levels initially remain constant, patients experience fatigue and exhaustion due to reduced cellular iron levels and reduction in aerobic metabolism. Intravenous iron rapidly improves muscle function in days, increasing fitness before an effect on haemoglobin levels are seen. 7 Abstracts of the 19th Annual NATA Symposium Speaker Abstracts S6 Anaemia at discharge ‒ what should be done? E. Bisbe Department of Anaesthesiology, Hospital Mar-Esperança, Barcelona, Spain Postoperative anaemia is primarily cause by perioperative bleeding, although it is exacerbated or maintained by the inflammatory response to surgical aggression.1 The first consequence is the administration of red blood cell transfusion (RBCT). Available evidence shows that a restrictive transfusion threshold does not increase morbidity or mortality, even in elderly patients with cardiovascular risk.2 Application of restrictive transfusion thersholds has resulted in significant postoperative anaemia that may be accompanied of iron deficiency3,4 that could hamper early rehabilitation and return to daily activities. Treatment of postoperative anaemia is part of the first pillar of Patient Blood Management and aims at avoiding RBCT and improving postoperative outcome, although it could also improve physical performance.5 According to the pathophysiology of postoperative anaemia, perioperative bleeding implies a considerable loss of iron and inflammation-mediated hepcidin increase inhibits intestinal absorption of iron.6 Thus, postoperative oral iron is not useful and is therefore not recommended (Grade 1B).7 Intravenous iron could have an important role in its management, even administered preoperatively, as it has been demonstrated that it improves haemoglobin at discharge.6,8 REFERENCES 1. Van Iperen CE, Kraaijenhagen RJ, Biesma DH, Beguin Y, Marx JJ, van de Wiel A. Iron metabolism and erythropoiesis after surgery. Br J Surg 1998; 85: 41-5 2. Carson JL, Terrin ML, Noveck H, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med 2011; 365: 2453-62 3. Lasocki S, Krauspe R, von Heymann C, Mezzacasa A, Chainey S, Spahn DR. PREPARE: the prevalence of perioperative anaemia and need for patient blood management in elective orthopaedic surgery: a multicentre, observational study. Eur J Anaesthesiol 2015; 32: 160-7 4. Shander A, Knight K, Thurer R, Adamson J, Spence R. Prevalence and outcomes of anemia in surgery: a systematic review of the literature. Am J Med 2004; 116 Suppl 7A: 58S-69S 5. Bisbe Vives E, Molto L. [Therapeutic approach to postoperative anemia]. Rev Esp Anestesiol Reanim 2015; 62 Suppl 1: 41- 4 6. Bisbe E, Molto L, Arroyo R, Muniesa JM, Tejero M. Randomized trial comparing ferric carboxymaltose vs oral ferrous glycine sulphate for postoperative anaemia after total knee arthroplasty. Br J Anaesth 2014; 113: 402-9. 7. Leal-Noval SR, Muñoz M, Asuero M, et al. Spanish Consensus Statement on alternatives to allogeneic blood transfusion: the 2013 update of the “Seville Document”. Blood Transfus 2013; 11: 585-610 8. Froessler B, Palm P, Weber I, Hodyl NA, Singh R, Murphy EM. The important role for intravenous iron in perioperative patient blood management in major abdominal surgery: a randomized controlled trial. Ann Surg 2016; 264: 41-6 8 Abstracts of the 19th Annual NATA Symposium Speaker Abstracts Weighing the Evidence for Coagulation Therapies in Cardiac Surgery (Session organised in collaboration with the European Association of Cardiothoracic Anaesthesiology) S7 Lessons learned from writing the EACTS/EACTA patient blood management guidelines C. Boer Department of Anaesthesiology, Amsterdam Cardiovascular Sciences, VU University Medical Centre, Amsterdam, the Netherlands In January 2018, the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association for Cardiothoracic Anaesthesiology (EACTA) published their 2017 Guidelines on Patient Blood Management for Adult Cardiac Surgery. Until recently, patient blood management in cardiac surgery was an unpopular theme in most cardiosurgical journals. However, increased awareness of the multidisciplinary aspect of patient blood management has led to the collaboration of surgeons and anaesthesiologists in the current guideline. In order to reach consensus for the different topics described in the guideline, surgeons and anaesthesiologists worked in pairs. It was a challenge to integrate the individual views from both sides, and to present a proper definition of the level of evidence for the different recommendations in the guideline. One challenge was to separate evidence and opinion, and in some cases, this required subsequent discussions. A second challenge was the lack of evidence for many commonly used interventions, such as the use of fibrinogen concentrate to treat coagulopathy after cardiopulmonary bypass. The number and quality of studies available on the effectiveness of fibrinogen is very low, and these recommendations had to be handled very sensitively. A difficult topic was the definition of a bleeding algorithm in cardiac surgery. While many investigators aim to institute a step-wise protocol for the treatment of bleeding, the guideline task force concluded that the introduction of a bleeding algorithm in an institution might already be beneficial in reducing blood transfusions, without putting emphasis on the cut-off values for coagulation treatment strategies. The most important lesson learned from writing the guideline is that patient blood management in cardiac surgery can only be successful in case of a multidisciplinary and multifactorial approach. Future updates of the patient blood management guidelines should also involve the European Board of Cardiovascular Perfusion to close the triangular relationship between the surgeon, the anaesthesiologist and the perfusionist. 9 Abstracts of the 19th Annual NATA Symposium Speaker Abstracts S8 The story of fibrinogen C. von Heymann Department of Anaesthesia, Intensive Care Medicine, Emergency Medicine, and Pain Therapy, Vivantes Klinikum im Friedrichshain, Berlin, Germany Fibrinogen is the substrate of coagulation and a major constant of clot formation and firmness of the clot.1 This describes the extraordinary role and function to secure haemostasis by timely clot formation. Timely clot formation is even more important in the setting of perioperative medicine as surgery requires sufficient and quick haemostasis. For decades fibrinogen administration in the perioperative setting relied on therapeutic plasma or cryoprecipitate.2 A fibrinogen concentrate, however, was mainly indicated for rare coagulation disorders as hypofibrinogenaemia or dysfibrinogenaemia and not available in all parts of the world. In recent years more and more presentations and retrospective analyses reported on the successful and effective administration of fibrinogen concentrate in the perioperative setting.3 Prospective randomised and placebo- controlled trials showed controversial results in reducing blood loss and transfusion requirements in major vascular surgery involving cardiopulmonary bypass.4-6 Other controlled data in complex cardiac surgery confirmed inhomogeneous results the efficacy of fibrinogen supplementation.7,8 Recent meta-analyses confirm a significant reduction in blood loss and transfusion requirements, but a high risk of bias of the existing studies still prevents further conclusions and asks for more sufficiently powered prospective trials.9,10 This lecture focuses on the evidence from controlled data on fibrinogen supplementation in cardiac surgery with regard to its efficacy and safety in terms of thromboembolic complications. The presentation will conclude with a critical appraisal on the advantages and limitations of fibrinogen concentrate compared to other therapeutical sources for fibrinogen supplementation. REFERENCES 1. Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008; 451: 914-8 2. Levy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion 2014; 54: 1389-405 3. Rahe-Meyer N, Solomon C, Winterhalter M, et al. Thromboelastometry-guided administration of fibrinogen concentrate for the treatment of excessive intraoperative bleeding in thoracoabdominal aortic aneurysm surgery. J Thorac Cardiovasc Surg 2009; 138: 694-702 4. Rahe-Meyer N, Solomon C, Hanke A, et al. Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: a randomized, placebo-controlled trial. Anesthesiology 2013; 118: 40-50 5. Rahe-Meyer N, Levy JH, Mazer CD, et al. Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy. Br J Anaesth 2016; 117: 41-51 6. Ranucci M, Baryshnikova E, Crapelli GB, Rahe-Meyer N, Menicanti L, Frigiola A. Randomized, double-blinded, placebo- controlled trial of fibrinogen concentrate supplementation after complex cardiac surgery. J Am Heart Assoc 2015; 4: e002066 7. Jeppsson A, Waldén K, Roman-Emanuel C, Thimour-Bergstrom L, Karlsson M. Preoperative supplementation with fibrinogen concentrate in cardiac surgery: A randomized controlled study. Br J Anaesth 2016; 116: 208-14 8. Bilecen S, de Groot JA, Kalkman CJ, et al. Effect of fibrinogen concentrate on intraoperative blood loss among patients with intraoperative bleeding during high-risk cardiac surgery: a randomized clinical trial. JAMA 2017; 317: 738-47 9. Gielen C, Dekkers O, Stijnen T, et al. The effects of pre- and postoperative fibrinogen levels on blood loss after cardiac surgery: a systematic review and meta-analysis. Interact Cardiovasc Thorac Surg 2014; 18: 292-8 10. Fominskiy E, Nepomniashchikh VA, Lomivorotov VV, et al. Efficacy and safety of fibrinogen concentrate in surgical patients: a meta-analysis of randomized controlled trials. J Cardiothorac Vasc Anesth 2016; 30: 1196-204 10