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Impact of Fibrinogen Infusion on Thrombin Generation and Fibrin Clot Structure in Patients with Inherited AfibrinogenemiaFunding This study was funded by Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (grant # 31003A_172864) to Marguerite Neerman-Arbez.
Introduction Inherited afibrinogenemia is a very rare disease characterized by complete absence of fibrinogen in the circulation and an increased risk in both thrombosis and bleeding. Infusion of fibrinogen concentrate (FC) is the main approach for prevention and management of bleeding; however, it has been reported to carry a thrombotic risk.
Methods We investigated the impact of a standard dose (40–100 mg/kg) of FC infusion on the thrombin generation (TG) parameters and the fibrin clot structure formed in plasma samples of patients with afibrinogenemia. Blood samples were collected from 20 patients before (T0) and 1 hour after infusion of FC (T1). TG was studied with calibrated automated thrombography. Fibrin clot structure was assessed with turbidimetry and scanning electron microscopy.
Results FC infusions (mean Clauss fibrinogen plasma level: 1.21 g/L at T1) led to a statistically significant increase in endogenous thrombin potential (ETP) (p < 0.0001) and thrombin peaks (p = 0.02). Nevertheless, when compared with healthy controls, patients' T1 lag times were longer (p = 0.002), ETP values were lower (p = 0.0003), and thrombin peaks were lower (p < 00001). All fibrin polymerization parameters (turbidimetry) obtained at T1 were comparable to those of patients with inherited hypofibrinogenemia matched for fibrinogen plasma levels.
Conclusion In summary, fibrinogen infusion with a standard dose of FC increased but did not correct TG and led to formation of fibrin clots similar to those of patients with hypofibrinogenemia. All in all, our results do not support the biological evidence of hypercoagulability induced by FC in patients with afibrinogenemia.
C.K., T.L., M.N.-A., and A.C. designed the study, analyzed the data, and wrote the paper; R.M. designed and performed experiments, analyzed the data, and wrote the paper; S.D. designed and performed experiments.
* These authors contributed equally to this work.
Received: 10 November 2021
Accepted: 18 January 2022
Accepted Manuscript online:
19 January 2022
Article published online:
14 March 2022
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