Perioperative bleeding: understanding causes, mechanisms and novel management approaches

Perioperative bleeding represents a significant clinical challenge that impacts patient outcomes, prolongs recovery times and increases healthcare costs. This multifactorial condition arises from various causes, including surgical factors, coagulopathies, and the use of anticoagulants and antiplatelet agents. The management of perioperative bleeding is further complicated by the increasing use of novel anticoagulants and the presence of congenital or acquired bleeding disorders. This review discusses the pathophysiology of coagulation, the mechanisms contributing to perioperative bleeding, and current management strategies, particularly in patients undergoing anticoagulation therapy, while also exploring emerging technologies and therapies such as hemoadsorption devices, novel anticoagulant reversal strategies, point-of-care testing and evolving anticoagulant adsorbers. Overall, our findings highlight the critical need for individualized, evidence-based management strategies, and further research to optimize perioperative anticoagulation protocols and improve surgical outcomes.

Perioperative bleeding; Anticoagulants; Antiplatelet drugs; Point-of-care testing; Hemoadsorption

[1] Douketis JD, Spyropoulos AC. Perioperative management of patients taking direct oral anticoagulants: a review. JAMA. 2024; 332: 825–834.

[2] Matejic-Spasic M, Hassan K, Thielmann M, Geidel S, Storey RF, Schmoeckel M, et al. Management of perioperative bleeding risk in patients on antithrombotic medications undergoing cardiac surgery—a systematic review. Journal of Thoracic Disease. 2022; 14: 3030–3044.

[3] Tripathi R, Morales J, Lee V, Gibson CM, Mack MJ, Schneider DJ, et al. Antithrombotic drug removal from whole blood using Haemoadsorption with a porous polymer bead sorbent. European Heart Journal—Cardiovascular Pharmacotherapy. 2022; 8: 847–856.

[4] Medcrine. Coagulation cascade and hemostasis. 2024. Available at: https://medcrine.com (Accessed: 27 January 2025).

[5] Hemostasis.com. Coagulation cascade. 2025. Available at: https://hemostasis.com (Accessed: 27 January 2025).

[6] Pagano D, Milojevic M, Meesters MI, Benedetto U, Bolliger D, von Heymann C, et al. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. European Journal of Cardio-Thoracic Surgery. 2018; 53: 79–111.

[7] Tibi P, McClure RS, Huang J, Baker RA, Fitzgerald D, Mazer CD, et al. STS/SCA/AmSECT/SABM update to the clinical practice guidelines on patient blood management. The Annals of Thoracic Surgery. 2021; 112: 981–1004.

[8] Rossini R, Tarantini G, Musumeci G, Masiero G, Barbato E, Calabrò P, et al. A Multidisciplinary approach on the perioperative antithrombotic management of patients with coronary stents undergoing surgery. JACC: Cardiovascular Interventions. 2018; 11: 417–434.

[9] Lenasi H. Haemostasis. Medicinski Razgledi. 2017; 56: 197–214.

[10] Lippi G, Favaloro E, Franchini M, Guidi G. Milestones and perspectives in coagulation and hemostasis. Seminars in Thrombosis and Hemostasis. 2009; 35: 9–22.

[11] Mayo Clinic. Von Willebrand disease. 2025. Available at: https://www.mayoclinic.org/diseases-conditions/von-willebrand-disease/symptoms-causes/syc-20354978#overview (Accessed: 27 January 2025).

[12] Ghosh K, Shetty S. Epidemiology, diagnosis, and management of von Willebrand disease in India. Seminars in Thrombosis and Hemostasis. 2011; 37: 595–601.

[13] Sabate A, Scarlatescu E. Treating periprocedural bleeding in patients with cirrhosis. Journal of Thrombosis and Thrombolysis. 2024; 57: 531–536.

[14] Malkhassian D, Sabir S, Sharma S. Physiology, factor XIII. 2023. Available at: https://www.ncbi.nlm.nih.gov/books/NBK538271/ (Accessed: 17 March 2025).

[15] Samuelson BT, Cuker A. Measurement and reversal of the direct oral anticoagulants. Blood Reviews. 2017; 31: 77–84.

[16] Brahim O, Mesrati MA, Limem H, Boussaid M, Soiniya R, Ben Abdeljelil N, et al. Life-threatening spontaneous splenic rupture in congenital afibrinogenemia: two case reports and systematic literature review. Journal of Forensic and Legal Medicine. 2025; 109: 102808.

[17] Pishko AM, Doshi BS. Acquired hemophilia a: current guidance and experience from clinical practice. Journal of Blood Medicine. 2022; 13: 255–265.

[18] Rezende SM, Neumann I, Angchaisuksiri P, Awodu O, Boban A, Cuker A, et al. International Society on Thrombosis and Haemostasis clinical practice guideline for treatment of congenital hemophilia a and B based on the Grading of Recommendations Assessment, Development, and Evaluation methodology. Journal of Thrombosis and Haemostasis. 2024; 22: 2629–2652.

[19] Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). Journal of Thrombosis and Haemostasis. 2006; 4: 295–306.

[20] Gómez-Outes A, Suárez-Gea ML, Lecumberri R, Terleira-Fernández AI, Vargas-Castrillón E. Direct-acting oral anticoagulants: pharmacology, indications, management, and future perspectives. European Journal of Haematology. 2015; 95: 389–404.

[21] Federici AB, Budde U, Castaman G, Rand JH, Tiede A. Current diagnostic and therapeutic approaches to patients with acquired von Willebrand syndrome: a 2013 update. Seminars in Thrombosis and Hemostasis. 2013; 39: 191–201.

[22] Levy JH, Shaw JR, Castellucci LA, Connors JM, Douketis J, Lindhoff-Last E, et al. Reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. Journal of Thrombosis and Haemostasis. 2024; 22: 2889–2899.

[23] Kietaibl S, Ahmed A, Afshari A, Albaladejo P, Aldecoa C, Barauskas G, et al. Management of severe peri-operative bleeding: guidelines from the European Society of Anaesthesiology and Intensive Care. European Journal of Anaesthesiology. 2023; 40: 226–304.

[24] Kozek-Langenecker SA, Afshari A, Albaladejo P, Santullano CAA, De Robertis E, Filipescu DC, et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. European Journal of Anaesthesiology. 2013; 30: 270–382.

[25] Gosselin R, Adcock D, Bates S, Douxfils J, Favaloro E, Gouin-Thibault I, et al. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of direct oral anticoagulants. Thrombosis and Haemostasis. 2018; 118: 437–450.

[26] Tornkvist M, Smith JG, Labaf A. Current evidence of oral anticoagulant reversal: a systematic review. Thrombosis Research. 2018; 162: 22–31.

[27] Ansell J, Hirsh J, Dalen J, Bussey H, Anderson D, Poller L, et al. Managing oral anticoagulant therapy. Chest. 2001; 119: 22S–38S.

[28] Gressenberger P. Reversal strategies in patients treated with direct oral anticoagulants. Vasa. 2019; 48: 389–392.

[29] Shaw JR, Siegal DM. Pharmacological reversal of the direct oral anticoagulants—a comprehensive review of the literature. Research and Practice in Thrombosis and Haemostasis. 2018; 2: 251–265.

[30] Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI. Parenteral anticoagulants: American college of chest physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008; 133: 141S–159S.

[31] Crivellari M, Landoni G, D’Andria Ursoleo J, Ferrante L, Oriani A. Protamine and heparin interactions: a narrative review. Annals of Cardiac Anaesthesia. 2024; 27: 202–212.

[32] Deng H, Shi C, Li G, Luo J, Wang Z, Lin Y, et al. The safety profile of preoperative administration of heparin for thromboprophylaxis in Chinese patients intended for thoracoscopic major thoracic surgery: a pilot randomized controlled study. Journal of Thoracic Disease. 2017; 9: 1065–1072.

[33] Hirsh J, O’Donnell M, Weitz JI. New anticoagulants. Blood. 2005; 105: 453–463.

[34] Mahaffey KW, Lewis BE, Wildermann NM, Berkowitz SD, Oliverio RM, Turco MA, et al.; ATBAT Investigators. The anticoagulant therapy with bivalirudin to assist in the performance of percutaneous coronary intervention in patients with heparin-induced thrombocytopenia (ATBAT) study: main results. The Journal of Invasive Cardiology. 2003; 15: 611–616.

[35] Lewis BE, Wallis DE, Berkowitz SD, Matthai WH, Fareed J, Walenga JM, et al. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation. 2001; 103: 1838–1843.

[36] Stanger L, Yamaguchi A, Holinstat M. Antiplatelet strategies: past, present, and future. Journal of Thrombosis and Haemostasis. 2023; 21: 3317–3328.

[37] Douketis JD, Spyropoulos AC. Perioperative management of anticoagulant and antiplatelet therapy. NEJM evidence. 2023; 2: EVIDra2200322.

[38] van Turenhout EC, Bossers SM, Loer SA, Giannakopoulos GF, Schwarte LA, Schober P. Pre‐hospital transfusion of red blood cells. Part 1: a scoping review of current practice and transfusion triggers. Transfusion Medicine. 2020; 30: 86–105.

[39] Loss L, Tinoco-Garcia L, Schreiber M. Resuscitative adjuncts and alternative products when blood supplies are limited. Trauma Surgery & Acute Care Open. 2024; 9: e001415.

[40] Levy JH, Ghadimi K, Quinones QJ, Bartz RR, Welsby I. Adjuncts to blood component therapies for the treatment of bleeding in the intensive care unit. Transfusion Medicine Reviews. 2017; 31: 258–263.

[41] O’Connell KA, Wood JJ, Wise RP, Lozier JN, Braun MM. Thromboembolic adverse events after use of recombinant human coagulation factor VIIa. JAMA. 2006; 295: 293–298.

[42] Žunić M, Vreča N, Bevc S. The role of factor XIII in patient blood management. Blood Coagulation & Fibrinolysis. 2024; 35: 325–333.

[43] Veigas PV, Callum J, Rizoli S, Nascimento B, da Luz LT. A systematic review on the rotational thrombelastometry (ROTEM®) values for the diagnosis of coagulopathy, prediction and guidance of blood transfusion and prediction of mortality in trauma patients. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2016; 24: 114.

[44] Spahn DR, Bouillon B, Cerny V, Duranteau J, Filipescu D, Hunt BJ, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Critical Care. 2019; 23: 98.

[45] Schmoeckel M, Thielmann M, Vitanova K, Eberle T, Marczin N, Hassan K, et al. Direct-acting oral anticoagulant removal by intraoperative hemoadsorption in CABG and/or single valve surgery: interim analysis of the International Safe and Timely Antithrombotic Removal (STAR) registry. Journal of cardiothoracic surgery. 2025; 20: 74.

[46] Hassan K, Kannmacher J, Wohlmuth P, Budde U, Schmoeckel M, Geidel S. Cytosorb adsorption during emergency cardiac operations in patients at high risk of bleeding. The Annals of Thoracic Surgery. 2019; 108: 45–51.

[47] Angheloiu AA, Angheloiu GO. Removal of dabigatran using sorbent hemadsorption. International Journal of Cardiology. 2019; 293: 73–75.

[48] Honore PM, Mugisha A, Kugener L, Redant S, Attou R, Gallerani A, et al. Austrian recommendations for best clinical practice in case of haemorrhagic traumatic brain injury under platelet inhibitors or non-vitamin K antagonist oral anticoagulants: an additional therapeutic option to consider. Critical Care. 2020; 24: 204.

[49] Angheloiu AA, Tan Y, Ruse C, Shaffer SA, Angheloiu GO. In-vitro sorbent-mediated removal of edoxaban from human plasma and albumin solution. Drugs in R&D. 2020; 20: 217–223.

[50] Angheloiu GO, Gugiu GB, Ruse C, Pandey R, Dasari RR, Whatling C. Ticagrelor removal from human blood. JACC: Basic to Translational Science. 2017; 2: 135–145.

[51] Hassan K, Bruening T, Bein B, Caspary M, Wohlmuth P, Geidel S, et al. Hemadsorption treatment for antithrombotic drug removal in emergency cardiac surgery—cost-benefit analysis comparing patient outcomes. European Heart Journal. 2022; 43: ehac544.1279.

[52] Hassan K, Brüning T, Caspary M, Wohlmuth P, Pioch H, Schmoeckel M, et al. Hemoadsorption of rivaroxaban and ticagrelor during acute type A aortic dissection operations. Annals of Thoracic and Cardiovascular Surgery. 2022; 28: 186–192.

[53] Røed-Undlien H, Schultz NH, Husebråten IM, Wollmann BM, Akerkar RR, Molden E, et al. Apixaban removal during emergency surgery for type A acute aortic dissection: a prospective cohort study. International Journal of Surgery. 2024; 110: 7782–7790.

[54] Koertge A, Wasserkort R, Wild T, Mitzner S. Extracorporeal hemoperfusion as a potential therapeutic option for critical accumulation of rivaroxaban. Blood Purification. 2018; 45: 126–128.