Factor XII deficiency evaluated by thrombin generation assay

Abstract

Introduction: Coagulation factor XII (FXII) plays a role in thrombin generation, fibrinolysis, inflammation, angiogenesis, chemotaxis and diapedesis. FXII deficiency is not associated with bleeding risk unlike other coagulation factors.

Materials/methods: We investigated thrombin generation assay (TGA) profile modification in FXII deficiency and the correlation with TGA and deficiency severity. TGA was performed in platelet poor plasma (PPP) with tissue factor (1 pmol/L) and phospholipid (4 µmol/L) standardized concentration. Thrombin generation profiles were compared in 54 patients with FXII deficiency, 25 healthy controls and 23 patients with hemophilia A (factor VIII (FVIII) deficiency. Patients with FXII deficiency were classified in three groups based on FXII activity (30-50%, 10-29%, <10%). FVIII deficiency was included as a bleeding control group.

Results: As expected, we found a correlation between FXII deficiency and activated partial thromboplastin time (aPTT). A decrease of thrombin generation was observed in healthy controls and all FXII deficiency groups. A decrease of endogenous thrombin potential (ETP), peak and velocity was observed in patients with FVIII deficiency compared to FXII deficiency. A decrease of thrombin generation was noted in patients with FXII deficiency and bleeding history compared to patients with FXII deficiency and thrombosis history.

Conclusion: In this study, thrombin generation profiles were not sensitive to FXII deficiency. TGA could distinguish bleeding and thrombotic tendency in FXII deficiency. Our results should therefore be considered as exploratory and deserve confirmation.

Keywords: Bleeding; Factor XII deficiency; Thrombin generation assay.