title: Use of thromboelastography and thrombin generation assay to predict clinical phenotype in patients with severe FVII deficiency.
abstract: Bleeding tendency is weakly correlated with the activity of factor VII (FVII) in the plasma of patients with FVII deficiency. A laboratory method for predicting bleeding risk in patients with this coagulation disorder is lacking. We investigated whether global coagulation assays, specifically thromboelastography (TEG) and thrombin generation assay (TGA), could be used to predict bleeding risk. We also sought to identify factors that may explain the differences in bleeding phenotype observed among individuals with severe FVII deficiency. The study comprised 12 patients with severe FVII deficiency (FVII activity <1%). Eleven patients were homozygous for the Gln100Arg mutation and one patient was compound heterozygous. Clinically, 10 patients had increased haemorrhagic diathesis, whereas two patients were asymptomatic. Blood sampling was performed at baseline for TEG and TGA analyses. The platelet aggregation assay was performed and the plasma level of anticoagulation inhibitors and thrombophilic risk factors assessed. No difference in the TEG and TGA results was observed in all FVII-deficient individuals. The level of free tissue factor pathway inhibitor was within the normal range and similar in symptomatic and asymptomatic subjects. None of the participants had the FV Leiden mutation, prothrombin gene mutation, or abnormal anticoagulant inhibitor levels. Asymptomatic subjects showed normal platelet aggregation. These data suggested that TEG and TGA were not suitable methods for predicting the clinical phenotype in FVII-deficient subjects.
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Haematology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: H T T
authors.initials: HT
authors.lastname: Tran
authors.forename: G E
authors.initials: GE
authors.lastname: Tjønnfjord
authors.forename: P A
authors.initials: PA
authors.lastname: Holme
mesh_terms: D000328:Adult; D000368:Aged; D001780:Blood Coagulation Tests; D005167:Factor VII / Q000235:genetics; D005168:Factor VII Deficiency / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006470:Hemorrhage / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D010974:Platelet Aggregation; D011379:Prognosis; D012720:Severity of Illness Index; D013916:Thrombelastography; D013917:Thrombin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D005167:Factor VII; D013917:Thrombin
keywords: bleeding risk; coagulation inhibitors; factor VII deficiency; geno-phenotype; thrombin generation assay; thromboelastography