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Perioperative Administration of Fibrinogen is Associated with Increased Risk of Postoperative Thromboembolic Complications after Cardiac Surgery

Carl-Johan Jakobsen, Mariann Tang and Lars Folkersen

Introduction: Fibrinogen is a key protein in achieving and maintaining haemostasis. Prophylactic fibrinogen has been shown to reduce bleeding after coronary artery bypass graft (CABG) and studies have reported an inverse correlation between preoperative plasma concentration of fibrinogen and the volume of postoperative bleeding after CABG. This indicates that preoperative fibrinogen plasma concentration, even within the normal range, is a limiting factor for haemostasis after cardiac surgery. In theory, fibrinogen might induce a risk for thrombosis and hypercoagulability. The reported adverse effects of fibrinogen administration are few, without clinical significance or blurred by the use of other medications influencing coagulation; the potential adverse effects of prophylactic fibrinogen on larger groups of cardiac surgery patients seem unidentified.

Material and methods: All patients undergoing cardiac surgery at Aarhus University Hospital in 2008 and 2009 were obtained from West Denmark Heart Registry (n=1876) and merged with our patient data management system to identify patients receiving fibrinogen, aprotinin and recombinant VIIa perioperatively. The outcomes considered included in-hospital myocardial infarction, stroke and need for dialysis. Model-based Poisson regression analysis was used to estimate adjusted risk ratios to identify independent factors with impact on outcomes.

Results: Independent risk factors (OR (95% CI)) for postoperative stroke were preoperative neurological dysfunction: 3.10 (1.46- 6.57), valve replacement: 2.12 (1.09 - 4.12), aortic surgery: 3.57 (1.35 - 9.46) and perioperative fibrinogen infusion: 2.69 (1.24 - 5.87). Independent risk factors for postoperative dialysis were s-creatinine > 200 µmol/L: 8.21 (4.12 - 16.5), age: 1.16 (1.00 - 1.33), Euroscore defined general-: 1.32 (1.17 - 1.48), and cardiac state: 1.27 (1.12 - 1.44) together with perioperative aprotinin: 3.42 (1.74 - 6.77) and fibrinogen infusion: 3.77 (2.02 - 7.03).

Conclusion: This study indicates that perioperative administration of fibrinogen could be associated with increased risk of neurological thromboembolic complication and renal failure and thus have potential thromboembolic side effects. However, further studies are warranted to clarify any causal association between postoperative complications and perioperative infusion of fibrinogen. The results further emphasized that administration of fibrinogen should be in accordance with recommended guidelines and always guided by whole blood coagulation evaluation.