Fibrinogen concentrate and risk of thromboembolic complications

Does fibrinogen concentrate increase the risk of thromboembolic complications and death when given to bleeding cardiac patients?

Waldén K, Jeppsson A, Nasic S, Karlsson M. Fibrinogen Concentrate to Cardiac Surgery Patients with Ongoing Bleeding does not Increase the Risk of Thromboembolic Complications or Death. Thromb Haemost. January 2020. doi:10.1055/s-0039-3402759

Fibrinogen concentrate is recommended as a replacement therapy in patients with major bleeding following surgery since it is one of the first coagulation factors to fall to critically low levels during ongoing bleeding (Hiippala et al., 1995; Kozek-Langenecker et al., 2017; Pagano et al., 2018; Spahn et al., 2019). Earlier, smaller studies have shown mixed findings on the role for procoagulant factor administration in the risk of thrombotic complications during surgery, and the contribution of fibrinogen concentrate to this risk remains unclear. Here, this large (N = 5,408), single-centre, retrospective study by Waldén and colleagues concluded that perioperative administration of fibrinogen concentrate to bleeding cardiac surgery patients is not associated with an increased risk of thromboembolic complications or death (Figure 1).

Figure 1. Adjusted primary and secondary end-points at 30 days or 1 year following cardiac surgery. *thromboembolic events or mortality or new revascularisation.

Waldén and colleagues report on a total of 5,408 patients who underwent first-time cardiac surgery at a single centre in Sweden. Patients who received fibrinogen concentrate (n = 564) at an average dose of 3.6 g (3.1–4.3 g) were compared to those who did not (n = 4,844). The primary endpoint was a composite of thromboembolic events and mortality one year following surgery, whereas secondary endpoints included the composite endpoint at 30 days, and mortality at 30 days and 1 year after surgery. Thromboembolic events included myocardial infarction, percutaneous or surgical revascularisation, ischaemic stroke, deep vein thrombosis, pulmonary embolism, thrombosis of the portal vein, peripheral arterial embolism and mesenterial arterial embolism.

Adjusting for perioperative variables, including transfusions as well as plasma fibrinogen concentration, the findings indicate that there is no significant difference in risk for the composite of mortality and thromboembolic events, mortality alone, or thromboembolic events alone for patients who received fibrinogen concentrate compared to those who did not (Figure 1). This is in line with smaller, earlier studies that found no difference in the incidence of thromboembolic events following fibrinogen concentrate administration based on propensity score matching of treatment groups (Fassl et al., 2015; Maeda et al., 2019).

In another earlier study which found an increased risk of postoperative stroke and renal failure in patients who received fibrinogen concentrate, propensity score matching was not carried out (Jakobsen et al., 2015). Here, unadjusted outcomes at both 30 days and 1 year following surgery also indicate that patients who received fibrinogen concentrate experienced significantly higher risk of mortality, or a composite of mortality and thromboembolic events (for both, P<0.001). However, this was not the case for thromboembolic events alone (P=0.31 at 30 days and P=0.44 at 1 year).

Of note, this study is the largest study to address this question; however, it is a retrospective single-centre observational study and further studies would be beneficial to understanding outcome.

Altogether, this large study concludes that fibrinogen concentrate administration does not impact on the risk of mortality and thromboembolic events in patients who experience bleeding during cardiac surgery.

Visit our learning zone section on the key clinical data for fibrinogen concentrate in treating patients who experience excessive bleeding during cardiac surgery.

References

Hiippala ST, Myllylä GJ, Vahtera EM. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg. 1995;81:360–365.

Jakobsen CJ, Tang M, Folkersen L. Perioperative administration of fibrinogen is associated with increased risk of postoperative thromboembolic complications after cardiac surgery. J Blood Disord Transfus. 2015;114:225–234.

Kozek-Langenecker SA, Ahmed AB, Afshari A, Albaladejo P, Aldecoa C, Barauskas G et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: first update 2016. Eur J Anaesthesiol. 2017;34:332–395.

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. Eur J Cardiothorac Surg. 2018;53:79–111.

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. Crit Care. 2019;23:98.

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;114:225–234.

Maeda T, Miyata S, Usui A, Nishiwaki K, Tanaka H, Okita Y et al. Safety of fibrinogen concentrate and cryoprecipitate in cardiovascular surgery: Multicenter database study. J Cardiothorac Vasc Anesth. 2019;33:321–327.