Tags

Type your tag names separated by a space and hit enter

Mild hemophilia A with factor VIII assay discrepancy: using thrombin generation assay to assess the bleeding phenotype.
J Thromb Haemost. 2008 Mar; 6(3):486-93.JT

Abstract

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 nM 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 nM min(-1), whereas for those of family Y they ranged from 447 to 1122 nM 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.

Authors+Show Affiliations

Centre Régional de Traitement de l'Hémophilie - Laboratoire d'Hématologie, Centre Hospitalier Universitaire, Nantes, France. marc.trossaert@chu-nantes.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18047548

Citation

Trossaërt, M, et al. "Mild Hemophilia a With Factor VIII Assay Discrepancy: Using Thrombin Generation Assay to Assess the Bleeding Phenotype." Journal of Thrombosis and Haemostasis : JTH, vol. 6, no. 3, 2008, pp. 486-93.
Trossaërt M, Regnault V, Sigaud M, et al. Mild hemophilia A with factor VIII assay discrepancy: using thrombin generation assay to assess the bleeding phenotype. J Thromb Haemost. 2008;6(3):486-93.
Trossaërt, M., Regnault, V., Sigaud, M., Boisseau, P., Fressinaud, E., & Lecompte, T. (2008). Mild hemophilia A with factor VIII assay discrepancy: using thrombin generation assay to assess the bleeding phenotype. Journal of Thrombosis and Haemostasis : JTH, 6(3), 486-93.
Trossaërt M, et al. Mild Hemophilia a With Factor VIII Assay Discrepancy: Using Thrombin Generation Assay to Assess the Bleeding Phenotype. J Thromb Haemost. 2008;6(3):486-93. PubMed PMID: 18047548.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mild hemophilia A with factor VIII assay discrepancy: using thrombin generation assay to assess the bleeding phenotype. AU - Trossaërt,M, AU - Regnault,V, AU - Sigaud,M, AU - Boisseau,P, AU - Fressinaud,E, AU - Lecompte,T, Y1 - 2007/11/28/ PY - 2007/12/1/pubmed PY - 2008/6/18/medline PY - 2007/12/1/entrez SP - 486 EP - 93 JF - Journal of thrombosis and haemostasis : JTH JO - J Thromb Haemost VL - 6 IS - 3 N2 - 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 nM 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 nM min(-1), whereas for those of family Y they ranged from 447 to 1122 nM 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. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/18047548/Mild_hemophilia_A_with_factor_VIII_assay_discrepancy:_using_thrombin_generation_assay_to_assess_the_bleeding_phenotype_ L2 - https://doi.org/10.1111/j.1538-7836.2007.02861.x DB - PRIME DP - Unbound Medicine ER -