Brazilian Journal of Anesthesiology
Brazilian Journal of Anesthesiology
Review Article

Efficacy and safety of antifibrinolytics in oncological surgery: a systematic review and meta‐analysis

Eficácia e segurança de antifibrinolíticos em cirurgia oncológica: uma revisão sistemática e metanálise

Aline Menezes Sampaio, Gabriel Magalhães Nunes Guimarães, Germano Pinheiro Medeiros, Germana Medeiros Mendes Damasceno, Ricardo Martins de Abreu Silva, Rogean Rodrigues Nunes, Hermano Alexandre Lima Rocha, José Carlos Rodrigues Nascimento

Downloads: 0
Views: 49


Background and objectives
The administration of antifibrinolytics has been shown to be effective in reducing blood loss and the need for transfusions in surgeries. However, few studies have evaluated these drugs in cancer surgery. The objective was to review the efficacy and safety of the treatment with antifibrinolytics in patients who underwent oncologic surgeries.

An electronic bibliographic research was conducted in PubMed, OVID, MEDLINE, EMBASE, EBSCO and in the Cochrane Library data basis in order to identify randomized clinical trials performed in any type of oncologic surgery. The data evaluated were blood loss, need for transfusion and incidence of arteriovenous thromboembolism. Five randomized controlled trials evaluating 838 patients met the inclusion requirements. In the analysis of the incidence of thromboembolic events in the five RCTs, there was no statistically significant difference between the administration of tranexamic acid when compared with the placebo (OR = 0.36, 95% IC: 0.11–1.19, p = 0.09, I2 = 0%). However, when total estimated blood loss and need for blood transfusion are analyzed, the use of tranexamic acid was associated with a significant reduction over placebo (MD = ‐135.79, 95% CI: ‐179.50 to ‐92.08, p < 0.00001, I2 = 68%) and (OR = 0.45, 95% CI: 0.32–0.65, p < 0.00001, I2 = 60%), respectively.

This meta‐analysis found no evidence that the administration of antifibrinolytics increases the risk of thromboembolic complications in patients submitted to oncologic surgery, and has shown evidence that it is effective in reducing total perioperative blood loss and the need for blood transfusion.


Antifibrinolytic agents; Cancer surgery; Thromboembolism; Blood loss


Justificativa e objetivos
A administração de agentes antifibrinolíticos mostrou ser eficaz para reduzir a perda sanguínea e a necessidade de transfusões em cirurgias. No entanto, poucos estudos avaliaram esses agentes em cirurgias oncológicas. O objetivo foi revisar a eficácia e segurança do tratamento com antifibrinolíticos em pacientes submetidos a cirurgias oncológicas.

Uma pesquisa bibliográfica foi conduzida nos bancos de dados eletrônicos PubMed, Ovid, Medline, Embase, Ebsco e na Biblioteca Cochrane para identificar estudos clínicos randômicos feitos em qualquer tipo de cirurgia oncológica. Os dados analisados foram perda sanguínea, necessidade de transfusão e incidência de tromboembolismo arteriovenoso. Cinco ensaios clínicos randômicos que avaliaram 838 pacientes atenderam aos critérios de inclusão. Na análise da incidência de eventos tromboembólicos em cinco ECR, não houve diferença estatisticamente significativa entre a administração do ácido tranexâmico, comparado ao placebo (OR = 0,36, IC 95%: 0,11‐1,19, p = 0,09; I2 = 0%). No entanto, quando a perda sanguínea total estimada e a necessidade de transfusão de sangue foram analisadas, o uso do ácido tranexâmico foi associado a uma redução significativa, comparado ao placebo. (DM: ‐135,79, IC 95%: ‐179,50 a ‐92,08, p < 0,00001, I2 = 68%) e (OR = 0,45, IC 95%: 0,32‐0,65, p < 0,00001, I2 = 60%), respectivamente.

Esta metanálise não encontrou evidências de que a administração de antifibrinolíticos aumente o risco de complicações tromboembólicas em pacientes submetidos à cirurgia oncológica e apresentou evidências de que é eficaz para reduzir a perda sanguínea total no perioperatório e a necessidade de transfusão de sangue.


Agentes antifibrinolíticos; Cirurgia oncológica; Tromboembolismo; Perda sanguínea


1 H.J. Alter, H.G. Klein The hazards of blood transfusion in historical perspective Blood, 112 (2008), pp. 2617-2626

2 K. Amer, S. Rehman, K. Amer, et al. Efficacy and safety of tranexamic acid in orthopedic fracture surgery: a meta‐analysis and systematic literature review J Orthop Trauma, 31 (2017), pp. 520-525

3 G.S. De Oliveira Jr., J.C. Schink, C. Buoy, et al. The association between allogeneic perioperative blood transfusion on tumour recurrence and survival in patients with advanced ovarian cancer Transfus Med, 22 (2012), pp. 97-103

4 T.S. Schiergens, M. Rentsch, M.S. Kasparek, K. Frenes, K.W. Jauch, W.E. Thasler Impact of perioperative allogeneic red blood cell transfusion on recurrence and overall survival after resection of colorectal liver metastases Dis Colon Rectum, 58 (2015), pp. 74-82

5 A.P. Kulkarni, D.A. Chaukar, V.P. Patil, et al. Does tranexamic acid reduce blood loss during head and neck cancer surgery Indian J Anaesth, 60 (2016), pp. 19-24

6 J.J. Andreasen Pharmacologic methods to reduce postoperative bleeding in adult cardiac surgery. A mini‐review Curr Pharm Des, 19 (2013), pp. 3992-3995

7 H.B. Zaid, D.Y. Yang, M.K. Tollefson, et al. Efficacy and safety of intraoperative tranexamic acid infusion for reducing blood transfusion during open radical cystectomy Urology, 92 (2016), pp. 57-62

8 A. Rannikko, A. Pétas, K. Taari Tranexamic acid in control of primary hemorrhage during transurethral prostatectomy Urology, 64 (2004), pp. 955-958

9 A. Crescenti, G. Borghi, E. Bignami, et al. Intraoperative use of tranexamic acid to reduce transfusion rate in patients undergoing radical retropubic prostatectomy: double blind, randomised, placebo controlled trial BMJ, 343 (2011), p. d5701

10 C. Kim, S.S.-H. Park, J.R. Davey Tranexamic acid for the prevention and management of orthopedic surgical hemorrhage: current evidence J Blood Med, 6 (2015), pp. 239-244

11 S. Alshryda, P. Sarda, M. Sukeik, et al. Tranexamic acid in total knee replacement: a systematic review and meta‐analysis J Bone Joint Surg Br, 93 (2011), pp. 1577-1585

12 A. Badenoch, A. Sharma, S. Gower, et al. The effectiveness and safety of tranexamic acid in orthotopic liver transplantation clinical practice: a propensity score matched cohort study Transplantation, 101 (2017), pp. 1658-1665

13 K. Ker, P. Edwards, P. Perel, et al. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta‐analysis BMJ, 344 (2012), p. e3054

14 D.A. Henry, P.A. Carless, A.J. Moxey, et al. Antifibrinolytic use for minimising perioperative allogeneic blood transfusion Cochrane Database Syst Rev (2011), p. CD001886

15 P.M. Mannucci, M. Levi Prevention and treatment of major blood loss N Engl J Med, 356 (2007), pp. 2301-2311

16 I.I. Modrau, L.L. Iversen, O.O. Thorlacius-Ussing Hemostatic alterations in patients with benign and malignant colorectal disease during major abdominal surgery Thromb Res, 104 (2001), pp. 309-315

17 R. Sud, A.A. Khorana Cancer‐associated trombosis: risk factors, candidate biomarkers and a risk model Thromb Res, 123 (2009), pp. S18-S21

18 J.W. Blom, C.J. Doggen, S. Osanto, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis JAMA, 293 (2005), pp. 715-722

19 P. Prandoni, A. Falanga, A. Piccioli Cancer and venous thromboembolism Lancet Oncol, 6 (2005), pp. 401-410

19 J.K. Wang, S.A. Boorjian, I. Frank, et al. Non‐O blood type is associated with an increased risk of venous thromboembolism after radical cystectomy Urology, 83 (2014), pp. 140-145

21 A.J. Sun, H. Djaladat, A. Schuckman, et al. Venous thromboembolism following radical cystectomy: significant predictors, comparison of different anticoagulants and timing of events J Urol, 193 (2015), pp. 565-569

22 I.Q. Molenaar, N. Warnaar, H. Groen, et al. Efficacy and safety of antifibrinolytic drugs in liver transplantation: a systematic review and meta‐analysis Am J Transplant, 7 (2007), pp. 185-194

23 J.H. Levy, A. Koster, Q.J. Quinones, et al. Antifibrinolytic therapy and perioperative considerations Anesthesiology, 128 (2018), pp. 657-670

24 S. Obaji, R. Alikhan, R. Rayment, et al. Unclassified bleeding disorders: outcome of haemostatic challenges following tranexamic acid and/or desmopressin Haemophilia, 22 (2016), pp. 285-291

25 E.S. Lundin, T. Johansson, H. Zachrisson, et al. Single‐dose tranexamic acid in advanced ovarian cancer surgery reduces blood loss and transfusions: double‐blind placebo‐controlled randomized multicenter study Acta Obstet Gynecol Scand, 93 (2014), pp. 335-344

26 S. Kvolik, M. Jukic, M. Matijevic, et al. An overview of coagulation disorders in cancer patients Surg Oncol, 19 (2010), pp. e33-e46

27 A. Gadducci, U. Baicchi, R. Marrai, et al. Pretreatment plasma levels of fibrinopeptide‐A (FPA) D‐dimer (DD), and von Willebrand factor (vWF) in patients with ovarian carcinoma Gynecol Oncol, 53 (1994), pp. 352-356

28 S.C. Koh, R. Khalil, F.K. Lim, A. Ilancheran, M. Choolani The association between fibrinogen, vonWillebrand Factor, antithrombin III, and D‐dimer levels and survival outcome by 36 months from ovarian cancer Clin Appl Thromb Hemost, 12 (2006), pp. 3-8

29 S. Sitalakshmi, K. Rameshkumar, P. Damodar Significance of haemostatic markers in ovarian carcinoma Indian J Med Paediatr Oncol, 29 (2008), pp. 6-10

30 J.P.T. Higgins, S. Green Cochrane handbook for systematic reviews of interventions. Version 333 5.1.0, The Cochrane Collaboration (2011) Available from: [atualização 03/2011]

31 R. DerSimonian, N. Laird Meta‐analysis in clinical trials Control Clin Trials, 7 (1986), pp. 177-188

32 C.C. Wu, W.M. Ho, S.B. Cheng, et al. Perioperative parenteral tranexamic acid in liver tumor resection: a prospective randomized trial toward a “blood transfusion”‐free hepatectomy Ann Surg, 243 (2006), pp. 173-180

33 N. Celebi, B. Celebioglu, M. Selcuk, et al. The role of antifibrinolytic agents in gynecologic cancer surgery Saudi Med J, 27 (2006), pp. 637-641

34 Ryan R, Hill S. How to GRADE the quality of the evidence. Cochrane Consumers and Communication Group. Available from:‐resources. Version 3.0 Dezembro 2016.

35 D. Amar, F.M. Grant, H. Zhang, et al. Antifibrinolytic therapy and perioperative blood loss in cancer patients undergoing major orthopedic surgery Anesthesiology, 98 (2003), pp. 337-342

36 C. Kietpeerakool, A. Supoken, M. Laopaiboon, P. Lumbiganon Effectiveness of tranexamic acid in reducing blood loss during cytoreductive surgery for advanced ovarian cancer Cochrane Database Syst Rev (2016) CD011732

37 K. Gupta, B. Rastogi, A. Krishan, A. Gupta, V.P. Singh, S. Agarwal The prophylactic role of tranexamic acid to reduce loss blood during radical surgery: a prospective study Anesth Essays Res, 6 (2012), pp. 70-73

38 J. Montroy, N.A. Fergusson, B. Hutton, et al. The safety and efficacy of lysine analogues in cancer patients: a systematic review and meta‐analysis Transfus Med Rev, 31 (2017), pp. 141-148

5dc5a9250e8825a214593254 rba Articles
Links & Downloads

Braz. J. Anesthesiol.

Share this page
Page Sections