Document Type : Original Research Article
Authors
- Shahram Sayadi 1
- Shideh Ariana 2
- Maral Hosseinzadeh 2
- Arezou Ashari 3
- Tannaz Yeganegi 1
- Elham Memari 1
- Ebtehaj Heshmatkhah 4
- Dariush Abtahi 5
1 Department of Anesthesiology, Anesthesia Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Obstetrics and Gynecology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of Community Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Department of Obstetrics and Gynecology, Imam Hossein Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5 Department of Anesthesiology, Clinical Research and Development Unit, Imam Hossein Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract
Background & Objective: Postpartum hemorrhage is the most common cause of maternal morbidity and mortality, which can occur unexpectedly without warning, and without any underlying causes. We hypothesized that administering fibrinogen concentrate to cesarean section patients before surgery would reduce perioperative blood loss.
Materials & Methods: In this double-blind randomized controlled parallel group study, a single dosage of fibrinogen concentrate or a placebo was given to 260 cesarean section patients at random (by G*Power software, Heinrich-Heine-Universität Düsseldorf, Germany) in a university-affiliated general hospital between November 11, 2022, to January 8, 2023. Individuals in the fibrinogen group received a dose of one gram of fibrinogen concentrate and those in the placebo group received normal saline solution with the same volume in the placebo group. Total blood loss was the primary outcome of this study.
Results: A total of 280 cases were screened and 260 were randomized. With a P-value of 0.001, the median (IQR) volume of bleeding in the fibrinogen group was 660 (341.25) mL, as opposed to 790 (475.00) mL in the placebo group. Comparatively, only 10 (7.7%) of the fibrinogen group and 26 (20%) of the placebo group required blood transfusions (P=0.006). No adverse event related to fibrinogen was reported.
Conclusion: Empiric treatment with fibrinogen concentrate results in reduced blood loss.
Highlights
✅ Empiric treatment with fibrinogen concentrate results in reduced blood loss.
Keywords
Main Subjects
1. Ghasemian Dizajmehr S, Mohammadi A, Malekshahi Nejad S. Efficacy of Uterine Artery Embolization for Control of Postpartum Hemorrhage. J Obstet Gynecol Cancer Res. 2023;8(1):63-7. [DOI:10.30699/jogcr.8.1.63]
2. Pourali L, Ayati S, Vatanchi A, Darvish A. Massive Postpartum Hemorrhage Following an Inner Myometrial Laceration: A Case Report. J Obstet Gynecol Cancer Res. 2022;4(1):42-4. [DOI:10.30699/jogcr.4.1.42]
3. Hogan MC, Foreman KJ, Naghavi M, Ahn SY, Wang M, Makela SM, et al. Maternal mortality for 181 countries, 1980-2008: a systematic analysis of progress towards Millennium Development Goal 5. Lancet. 2010;375(9726):1609-23. [DOI:10.1016/S0140-6736(10)60518-1] [PMID]
4. Borovac-Pinheiro A, Pacagnella RC, Cecatti JG, Miller S, El Ayadi AM, Souza JP, et al. Postpartum hemorrhage: new insights for definition and diagnosis. Am J Obstet Gynecol. 2018;219(2):162-8. [DOI:10.1016/j.ajog.2018.04.013] [PMID]
5. Belghiti J, Kayem G, Dupont C, Rudigoz R-C, Bouvier-Colle M-H, Deneux-Tharaux C. Oxytocin during labour and risk of severe postpartum haemorrhage: a population-based, cohort-nested case-control study. BMJ Open. 2011;1(2):e000514. [DOI:10.1136/bmjopen-2011-000514] [PMID] [PMCID]
6. Knight M, Callaghan WM, Berg C, Alexander S, Bouvier-Colle M-H, Ford JB, et al. Trends in postpartum hemorrhage in high resource countries: a review and recommendations from the International Postpartum Hemorrhage Collaborative Group. BMC Pregnancy Childbirth. 2009;9(1):1-10. [DOI:10.1186/1471-2393-9-55] [PMID] [PMCID]
7. Charbit B, Mandelbrot L, Samain E, Baron G, Haddaoui B, Keita H, et al. The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage. J Thromb Haemost. 2007;5(2):266-73. [DOI:10.1111/j.1538-7836.2007.02297.x] [PMID]
8. Cortet M, Deneux-Tharaux C, Dupont C, Colin C, Rudigoz RC, Bouvier-Colle MH, et al. Association between fibrinogen level and severity of postpartum haemorrhage: secondary analysis of a prospective trial. Br J Anaesth. 2012;108(6):984-9. [DOI:10.1093/bja/aes096] [PMID]
9. de Lloyd L, Bovington R, Kaye A, Collis RE, Rayment R, Sanders J, et al. Standard haemostatic tests following major obstetric haemorrhage. Int J Obstet Anesth. 2011;20(2):135-41. [DOI:10.1016/j.ijoa.2010.12.002] [PMID]
10. Jabalameli M, Zakeri K. Evaluation of Topical Tranexamic Acid on Intraoperative Bleeding in Endoscopic Sinus Surgery. Iran J Med Sci. 2006;31(4):221-3.
11. Mohammadi M, Nouri-Mahdavi K, Barzegar A. Effects of Tranexamic Acid on Bleeding and Hemoglobin Levels in Patients with Staghorn Calculi Undergoing Percutaneous Nephrolithotomy: Randomized Controlled Trial. Iran J Med Sci. 2019;44(6):457-64.
12. Mallaiah S, Barclay P, Harrod I, Chevannes C, Bhalla A. Introduction of an algorithm for ROTEM-guided fibrinogen concentrate administration in major obstetric haemorrhage. Anaesthesia. 2015;70(2):166-75. [DOI:10.1111/anae.12859] [PMID]
13. Shields LE, Wiesner S, Fulton J, Pelletreau B. Comprehensive maternal hemorrhage protocols reduce the use of blood products and improve patient safety. Am J Obstet Gynecol. 2015;212(3):272-80. [DOI:10.1016/j.ajog.2014.07.012] [PMID]
14. Gollop ND, Chilcott J, Benton A, Rayment R, Jones J, Collins PW. National audit of the use of fibrinogen concentrate to correct hypofibrinogenaemia. Transfus Med. 2012;22(5):350-5. [DOI:10.1111/j.1365-3148.2012.01168.x] [PMID]
15. Matsunaga S, Takai Y, Nakamura E, Era S, Ono Y, Yamamoto K, et al. The Clinical Efficacy of Fibrinogen Concentrate in Massive Obstetric Haemorrhage with Hypofibrinogenaemia. Sci Rep. 2017;7(1):46749. [DOI:10.1038/srep46749] [PMID] [PMCID]
16. Home U. Cryoprecipitate | Blood Transfusion Services 2022 [Available from: https://www.utmb.edu/bloodbank/component-therapy/cryoprecipitate.
17. Ahmed S, Harrity C, Johnson S, Varadkar S, McMorrow S, Fanning R, et al. The efficacy of fibrinogen concentrate compared with cryoprecipitate in major obstetric haemorrhage - an observational study. Transfus Med. 2012;22(5):344-9. [DOI:10.1111/j.1365-3148.2012.01178.x] [PMID]
18. Wikkelsoe AJ, Afshari A, Stensballe J, Langhoff-Roos J, Albrechtsen C, Ekelund K, et al. The FIB-PPH trial: fibrinogen concentrate as initial treatment for postpartum haemorrhage: study protocol for a randomised controlled trial. Trials. 2012;13(1):110. [DOI:10.1186/1745-6215-13-110] [PMID] [PMCID]
19. Collins PW, Cannings-John R, Bruynseels D, Mallaiah S, Dick J, Elton C, et al. Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage: OBS2, a double-blind randomized controlled trial. Br J Anaesth. 2017;119(3):411-21. [DOI:10.1093/bja/aex181] [PMID]
20. Rincón-Valenzuela DA, Bocanegra JC, Guevara J. Fibrinogn and postpartum hemorrhage-Association or causality? Colomb J Anesthesiol. 2017;45(2):136-9. [DOI:10.1016/j.rca.2017.02.004] [DOI:10.1016/10.1097/01819236-201704000-00011] [DOI:10.1016/j.rcae.2017.03.001]
21. Wikkelsø AJ, Edwards HM, Afshari A, Stensballe J, Langhoff-Roos J, Albrechtsen C, et al. Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial. Br J Anaesth. 2015;114(4):623-33. [DOI:10.1093/bja/aeu444] [PMID]
22. Fibrinogen Concentrate Use in an Academic Hospital: A Retrospective Study 2022. [Available from: http://www.asaabstracts.com/strands/asaabstracts/abstract.htm?year=2019&index=15&abs]
23. Innerhofer N, Treichl B, Rugg C, Fries D, Mittermayr M, Hell T, et al. First-Line Administration of Fibrinogen Concentrate in the Bleeding Trauma Patient: Searching for Effective Dosages and Optimal Post-Treatment Levels Limiting Massive Transfusion-Further Results of the RETIC Study. J Clin Med. 2021;10(17):3930. [DOI:10.3390/jcm10173930] [PMID] [PMCID]
24. Sadat Hosseini M, Abtahi D, Tajbakhsh A, Farzaneh F, Sayadi S, Amjadi N, et al. Evaluation of the Difference in Plasma Fibrinogen Levels Before and After Cesarean Section and its Association with Intra- and Postoperative Bleeding. J Obstet Gynecol Cancer Res. 2023;8(2):157-66.
25. Kelly M, Waldhauser H, Vilchez T, Dlotko E, Hutcheson R. Psu8 Comparing Costs of Using Fibrinogen Concentrate Versus Fresh Frozen Plasma in The Treatment of Bleeding During Cardiac Surgery in The Netherlands. Value Health. 2019;22:S893. [DOI:10.1016/j.jval.2019.09.2595]
26. Mallaiah S, Chevannes C, McNamara H, Barclay P. A reply. Anaesthesia. 2015;70(6):760-1. [DOI:10.1111/anae.13128] [PMID]
27. Solomon C, Gröner A, Jian Y, Inna P. Safety of fibrinogen concentrate: analysis of more than 27 years of pharmacovigilance data. J Thromb Haemost. 2015;113(04):759-71. [DOI:10.1160/TH14-06-0514] [PMID]
28. Djambas Khayat C, Lohade S, D'Souza F, Shamanur LG, Zekavat OR, Kruzhkova I, et al. Efficacy and safety of fibrinogen concentrate for on-demand treatment of bleeding and surgical prophylaxis in paediatric patients with congenital fibrinogen deficiency. Haemophilia. 2021;27(2):283-92. [DOI:10.1111/hae.14230] [PMID] [PMCID]
29. Ducloy-Bouthors AS, Mercier FJ, Grouin JM, Bayoumeu F, Corouge J, Le Gouez A, et al. Early and systematic administration of fibrinogen concentrate in postpartum haemorrhage following vaginal delivery: the FIDEL randomised controlled trial. Int J Gynaecol Obstet. 2021;128(11):1814-23. [DOI:10.1111/1471-0528.16699] [PMID]
30. Jarraya A, Khaled T, Kammoun M, Ameur K, Kolsi K. Golden hour for fibrinogen concentrate infusion to improve post partum hemorrhage. Egypt J Anaesth. 2018;34(2):73-4. [DOI:10.1016/j.egja.2018.03.002]
31. Bell SF, Rayment R, Collins PW, Collis RE. The use of fibrinogen concentrate to correct hypofibrinogenaemia rapidly during obstetric haemorrhage. Int J Obstet Anesth. 2010;19(2):218-23. [DOI:10.1016/j.ijoa.2009.08.004] [PMID]
32. Kikuchi M, Itakura A, Miki A, Nishibayashi M, Ikebuchi K, Ishihara O. Fibrinogen concentrate substitution therapy for obstetric hemorrhage complicated by coagulopathy. J Obstet Gynaecol Res. 2013;39(4):770-6. [DOI:10.1111/j.1447-0756.2012.02058.x] [PMID]
33. Callum J, Farkouh ME, Scales DC, Heddle NM, Crowther M, Rao V, et al. Effect of fibrinogen concentrate vs cryoprecipitate on blood component transfusion after cardiac surgery: the FIBRES randomized clinical trial. Jama. 2019;322(20):1966-76. [DOI:10.1001/jama.2019.17312] [PMID] [PMCID]
34. Fenger-Eriksen C, Lindberg-Larsen M, Christensen AQ, Ingerslev J, Sørensen B. Fibrinogen concentrate substitution therapy in patients with massive haemorrhage and low plasma fibrinogen concentrations. Br J Anaesth. 2008;101(6):769-73. [DOI:10.1093/bja/aen270] [PMID]
35. Rahe-Meyer N, Pichlmaier M, Haverich A, Solomon C, Winterhalter M, Piepenbrock S, et al. Bleeding management with fibrinogen concentrate targeting a high-normal plasma fibrinogen level: a pilot study. Br J Anaesth. 2009;102(6):785-92. [DOI:10.1093/bja/aep089] [PMID] [PMCID]
36. Solomon C, Pichlmaier U, Schoechl H, Hagl C, Raymondos K, Scheinichen D, et al. Recovery of fibrinogen after administration of fibrinogen concentrate to patients with severe bleeding after cardiopulmonary bypass surgery. Br J Anaesth. 2010;104(5):555-62. [DOI:10.1093/bja/aeq058] [PMID] [PMCID]
37. Sadeghi M, Atefyekta R, Azimaraghi O, Marashi SM, Aghajani Y, Ghadimi F, et al. A randomized, double blind trial of prophylactic fibrinogen to reduce bleeding in cardiac surgery. Rev Bras Anestesiol. 2014;64:253-7. [DOI:10.1016/j.bjan.2013.10.008] [PMID]
38. Fathi M, Lashay A, Massoudi N, Nooraei N, Nik MA. Fibrinogen prophylaxis for reducing perioperative bleeding in patients undergoing radical cystectomy: A double-blind placebo-controlled randomized trial. J Clin Anesth. 2021;73:110373. [DOI:10.1016/j.jclinane.2021.110373] [PMID]
39. Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and Laboratory Studies: A Reference Table for Clinicians. Obstet Gynecol. 2009;114(6). [DOI:10.1097/AOG.0b013e3181c2bde8] [PMID]
40. Siennicka A, Kłysz M, Chełstowski K, Tabaczniuk A, Marcinowska Z, Tarnowska P, et al. Reference Values of D-Dimers and Fibrinogen in the Course of Physiological Pregnancy: the Potential Impact of Selected Risk Factors-A Pilot Study. Biomed Res Int. 2020;2020. [DOI:10.1155/2020/3192350] [PMID] [PMCID]
41. Gong J-M, Shen Y, He Y-X. Reference Intervals of Routine Coagulation Assays During the Pregnancy and Puerperium Period. J Clin Lab Anal. 2016;30(6):912-7. [DOI:10.1002/jcla.21956] [PMID] [PMCID]
42. Cui C, Yang S, Zhang J, Wang G, Huang S, Li A, et al. Trimester-specific coagulation and anticoagulation reference intervals for healthy pregnancy. Thromb Res. 2017;156:82-6. [DOI:10.1016/j.thromres.2017.05.021] [PMID]
43. Innerhofer P, Westermann I, Tauber H, Breitkopf R, Fries D, Kastenberger T, et al. The exclusive use of coagulation factor concentrates enables reversal of coagulopathy and decreases transfusion rates in patients with major blunt trauma. Injury. 2013;44(2):209-16. [DOI:10.1016/j.injury.2012.08.047] [PMID]
44. Schöchl H, Nienaber U, Maegele M, Hochleitner G, Primavesi F, Steitz B, et al. Transfusion in trauma: thromboelastometry-guided coagulation factor concentrate-based therapy versus standard fresh frozen plasma-based therapy. Critical Care. 2011;15(2):1-9. [DOI:10.1186/cc10078] [PMID] [PMCID]
45. Era S, Matsunaga S, Matsumura H, Murayama Y, Takai Y, Seki H. Usefulness of shock indicators for determining the need for blood transfusion after massive obstetric hemorrhage. J Obstet Gynaecol Res. 2015;41(1):39-43. [DOI:10.1111/jog.12480] [PMID]
46. Wikkelsø A, Lunde J, Johansen M, Stensballe J, Wetterslev J, Møller AM, et al. Fibrinogen concentrate in bleeding patients. Cochrane Database Syst Rev. 2013;2013(8):Cd008864. [DOI:10.1002/14651858.CD008864.pub2] [PMID] [PMCID]
47. Matsunaga S, Takai Y, Seki H. Fibrinogen for the management of critical obstetric hemorrhage. J Obstet Gynaecol Res. 2019;45(1):13-21. [DOI:10.1111/jog.13788] [PMID] [PMCID]
48. Sahin AS, Ozkan S. Treatment of Obstetric Hemorrhage with Fibrinogen Concentrate. Med Sci Monit. 2019;25:1814-21. [DOI:10.12659/MSM.914234] [PMID] [PMCID]
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