Exogenous Fibrinogen Pertains Beneficial Effects in Managing Post-Cardiac Surgery Bleeding: A Randomized Clinical Trial

Document Type : Original Article


1 Anesthesiologist, Department Of Anesthesiology and Critical Care, Mashhad University of Medical Sciences, Mashhad, Iran

2 Anesthesiologist, Cardiac Anesthesia Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Anesthesiologist, Department of Anesthesiology and Critical Care, Mashhad University Of Medical Sciences, Mashhad, Iran

4 Cardiac Surgeon, Cardio-Thoracic Surgery & Transplant Research Center, Emam Reza hospital, Faculty of medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

5 Cardiac Surgeon, Department Of Cardiac Surgery, Kurdestan University Of Medical Sciences, Kordestan, Iran


Introduction: Post cardiac surgery hemorrhagic syndromes, potentialized by implementing cardiopulmonary bypass, leads to increased hazards of blood products transfusion and pertains serious impacts on immediate patients outcome.
The objective of this clinical trial was to investigate the efficiency of exogenous fibrinogen to control hemorrhagic syndromes following cardiac surgery in the intensive care unit.
Materials and Methods: Eighty patients undergoing open heart surgery at Imam Reza Hospital, Mashhad, Iran with blood drainage more than 200 ml per hour were randomly divided to receive either fibrinogen 2 grams or placebo. The patients were investigated for amount of blood drainage, units of required blood product, length of stay in intensive care unit (ICU), and mortality.
Results:  The first early 3-hours drainage (443.97±169.98 vs 606.66±235.93ml; p value =0.001) and total first 24 hours drainage (1025.30 ml and 1377.60 ml; p value: 0.041) showed significant difference in favor of fibrinogen receiving group. The fibrinogen group required significantly lesser units of red blood cells, and fresh frozen plasma (FFP) (1.62 and 2.55) compared to placebo group (2.74 and 3.21) (p values: 0.010 and 0.032). Platelets units requirement did not reach significant difference between the groups. ICU length of stay was shorter in fibrinogen group (2.82 days versus 4.02 days; p value 0.045), while mechanical ventilation time did not significantly differ among the two groups. In addition, there was a trend towards decreased  early mortality in fibrinogen receiving group (7.5% versus 17.5 % ; p value = 0.02).
Conclusion: Administration of low dose of fibrinogen in patients with postoperative bleeding can reduce ongoing and total blood drainage, transfusion of blood products, ICU length and early mortality.


1.Woodman RC, Harker LA. Bleeding complications associated with cardiopulmonary bypass. Blood. 1990;76:1680-97
2.  Görlinger K, Shore-Lesserson L, Dirkmann D, Hanke AA, Rahe-Meyer N, Tanaka KA.Management of hemorrhage in cardiothoracic surgery. J Cardiothorac Vasc Anesth.2013; 27:S20-34.
3. Biancari F, Mikkola R, Heikkinen J, Lahtinen J,  Airaksinen KEJ,  Juvonen T. Estimating the risk of complications related to re-exploration for bleeding after adult cardiac surgery: a systematic review and meta-analysis. Eur J Cardiothorac Surg. 2012; 41:  50–55
4. Tanaka KA, Egan K, Szlam F, Ogawa S, Roback JD, Sreeram G, et al. Transfusion and hematologic variables after fibrinogen or platelet transfusion in valve replacement surgery: preliminary data of purified lyophilized human fibrinogen concentrate versus conventional transfusion. Transfusion. 2014 ; 54:109-18
5.  Görlinger K, Dirkmann D, Hanke AA. Potential value of transfusion protocols incardiac surgery. Curr Opin Anaesthesiol. 2013 ;26 :230-43.
6.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. Braz J Anesthesiol. 2014  ;64:253-7
7. Karlsson M, Ternström L, Hyllner M, Baghaei F, Skrtic S, Jeppsson A.Prophylactic fibrinogen infusion in cardiac surgery patients: effects on biomarkers of coagulation, fibrinolysis, and platelet function. Clin Appl Thromb Hemost. 2011 ; 17:396-404.
8. Rahe-Meyer N, Solomon C, Hanke A, Schmidt DS, Knoerzer D, Hochleitner G, 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.
9. Rahe-Meyer N. Fibrinogen concentrate in the treatment of severe bleeding after aortic aneurysm graft surgery. Thromb Res. 2011;128 :S17-9.
10.  Ferraris VA, Brown JR, George J. Despotis GJ, Hammon JW, Reece B, et al.
2011 Update to The Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists Blood Conservation Clinical Practice Guidelines. Ann Thorac Surg 2011;91:944–82
11. Kristensen KL, Rauer LJ, Mortensen PE, Kjeldsen BJ. Reoperation for bleeding in cardiac surgery. Interactive CardioVascular and Thoracic Surgery.2012; 14: 709–71
12. Karkouti K, Callum J, Crowther MA, McCluskey SA, Pendergrast J, Tait G, et al. The relationship between fibrinogen levels after cardiopulmonary  bypass and large volume red cell transfusion in cardiac surgery: an observational study. Anesth Analg. 2013; 117:14-22.
13 Galas FR, de Almeida JP, Fukushima JT, Vincent JL, Osawa EA, Zeferino S, et al . Hemostatic effects of fibrinogen concentrate compared with cryoprecipitate in children after cardiac surgery: a randomized pilot trial. J Thorac Cardiovasc Surg. 2014 ;148:1647-55
14. Faraoni D, Willems A, Savan V, Demanet H, De Ville A, Van der Linden P. Plasma fibrinogen concentration is correlated with postoperative blood loss in children undergoing cardiac surgery. A retrospective review. Eur J Anaesthesiol. 2014;31:317-26
15. Pillai RC, Fraser JF, Ziegenfuss M, Bhaskar B. Influence of circulating levels of fibrinogen and perioperative coagulation parameters on predicting postoperative blood loss in cardiac surgery: a prospective observational study. J Card Surg. 2014 ;29:189-95
16. Gielen C, Dekkers O, Stijnen T, Schoones J, Brand A, Klautz R, 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.
17. Ranucci M(1), Jeppsson A, Baryshnikova E. Pre-operative fibrinogen supplementation in cardiac surgery patients: an evaluation of different trigger values. Acta Anaesthesiol Scand. 2015 ;59:427-33
18. Kindo M, Hoang Minh T, Gerelli S, Perrier S, Meyer N, Schaeffer M, et al. Plasma fibrinogen level on admission to the intensive care unit is a powerful predictor of postoperative bleeding after cardiac surgery with cardiopulmonary bypass. Thromb Res. 2014 ;134:360-8.
19.  Fassl J, Lurati Buse G, Filipovic M, Reuthebuch O, Hampl K, Seeberger MD, et al.Perioperative administration of fibrinogen does not increase adverse cardiac and thromboembolic events after cardiac surgery. Br J Anaesth. 2015 ;114:225-34
20. Stanzel R, Henderson M, O'Blenes S. Prophylactic fibrinogen administration during complex congenital cardiac surgery leading to thrombosis of a patient's brachial artery and the cardiopulmonary bypass circuit: a case report. Perfusion. 2013 ;29:369-372.
21. Bilecen S, Peelen LM, Kalkman CJ, Spanjersberg AJ, Moons KG, Nierich AP.Fibrinogen concentrate therapy in complex cardiac surgery. J Cardiothorac Vasc Anesth. 2013 ;27:12-17
22. Theusinger OM, Stein P, Levy JH. Point of care and factor concentrate-based coagulation algorithms. Transfus Med Hemother. 2015 ;42:115-21.
23. TEG®- or ROTEM®-based individualized goal-directed coagulation algorithms: don’t wait - act now!.Crit Care. 2014 ;18:637.
24. Ghavidel AA, Toutounchi Z, Shahandashti FJ, Mirmesdagh Y. Rotational thromboelastometry in prediction of bleeding after cardiac surgery. Asian Cardiovasc Thorac Ann. 2015 ;23:525-9.