Animal model and clinical evidence indicating low thrombogenic potential of fibrinogen concentrate (Haemocomplettan...

The objective of this study was to characterize the thrombogenicity of one pasteurized fibrinogen concentrate (Haemocomplettan P) in clinical use for over 20 years. Thrombus formation during venous stasis was assessed in rabbits receiving either 100 or 250 mg/kg Haemocomplettan P. Thrombotic adverse events possibly related to Haemocomplettan P were documented in a long-standing pharmacosurveillance program. A systematic review of thrombotic events in Haemocomplettan P clinical studies was also conducted. There was no evidence of thrombus formation during venous stasis in any Haemocomplettan P-treated animal. The pharmacosurveillance program spanned 22 years, during which a Haemocomplettan P quantity equivalent to more than 250 000 doses of 4 g each was distributed in 21 countries. Nine spontaneous reports of thrombotic adverse events possibly related to Haemocomplettan P were compiled, corresponding to an incidence rate of 3.48 events per 10 treatment episodes (95% confidence interval, 1.59-6.61 events per 10 treatment episodes). In 10 clinical studies involving 298 patients, one patient developed nonfatal venous thrombosis and pulmonary embolism to which fibrinogen concentrate may have contributed. Additionally, four other patients experienced arterial ischemic events that were likely attributable to massive hemorrhage and hypotension rather than fibrinogen replacement. Evidence from an animal model of venous stasis, a comprehensive pharmacosurveillance program, and a systematic review of clinical studies indicates that the thrombogenic potential of fibrinogen concentrate is low.