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Mild hemophilia A with factor VIII assay discrepancy: using thrombin generation assay to assess the bleeding phenotype
Author(s) -
TROSSAËRT M.,
REGNAULT V.,
SIGAUD M.,
BOISSEAU P.,
FRESSINAUD E.,
LECOMPTE T.
Publication year - 2008
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2007.02861.x
Subject(s) - thrombin generation , missense mutation , medicine , coagulation , chromogenic , clotting factor , thrombin , thromboelastography , gastroenterology , phenotype , immunology , platelet , chemistry , gene , biochemistry , chromatography
Summary. Introduction: In some patients with mild hemophilia A, there are discrepancies between 1‐stage (1‐st) and 2‐stage (2‐st) factor VIII (FVIII) clotting assays, and also chromogenic assays for FVIII activity (FVIII:C). We examined whether thrombography could provide a better evaluation of the hemostatic status of these patients. Methods: Two families with such discrepancies and markedly contrasting clinical histories were studied. Family X had no serious bleedings, in contrast to family Y. Sixty‐one moderate/mild hemophiliacs without discrepancy and 15 healthy subjects served as controls. Calibrated automated thrombography was performed with platelet‐rich plasma after one freeze‐thawing cycle and low tissue factor concentration. Results: The chromogenic FVIII:C levels were higher (0.90 ± 0.15 and 0.47 ± 0.13 IU mL −1 ) than the 1‐st clotting ones (0.14 ± 0.05 and 0.10 ± 0.05 IU mL −1 ) in family X and Y, respectively ( P < 0.001). Mean endogenous thrombin potential (ETP) was 1579 ± 359 n m min −1 and 1060 ± 450 for healthy controls and hemophilic controls, respectively. For members of family X, the ETP values were 1188, 1317 and 2277 n m min −1 , whereas for those of family Y they ranged from 447 to 1122 n m min −1 . Two novel missense point mutations were evidenced: p.Ile369Thr in family X and p.Phe2127Ser in family Y. In family X, we postulate that the mutation is responsible for a delayed but non‐deleterious FVIII activation. Conclusions: Our results suggest that the hemostatic phenotype assessed by thrombography may be clinically relevant in moderate/mild hemophilic patients with discrepant FVIII:C results.