Six novel missense mutations causing factor X deficiency and application of thrombin generation test.

Abstract

INTRODUCTION:

Inherited factor X (FX) deficiency is a rare hemorrhagic condition characterized by a variable clinical presentation weakly correlating with laboratory phenotype and genotype. Thrombin generation test (TGT) offers potential clinical advantages in the evaluation of hypocoagulable states.

MATERIALS AND METHODS:

Five FX assays were performed using clotting, chromogenic and immunological methods. The factor X gene (F10) defects were analyzed by direct sequencing. Thrombin generation (TG) was measured using a standard procedure with commercial reagents at 1 pM and 5 pM of tissue factor (TF). The influence of contact activation on TG at the two TF concentrations was analyzed by the addition of corn trypsin inhibitor (CTI).

RESULTS:

Seven missense mutations were identified in the F10 of the four probands with FX deficiency, six of which (Ser425Pro, Ala-29Pro, Phe324Leu, Ala235Thr, Cys111Arg and Met362Thr) were novel and associated with type I FX deficiency. TG measurements at 1 pM TF need the addition of CTI in both healthy individuals and FX-deficient patients. TG parameters of ETP, Peak and Rate correlated well with the FX:C levels and the clinical expressions of the FX-deficient patients at 1 pM TF with CTI. There is a higher sensitivity for FX deficiency at 1 pM TF compared with 5 pM TF in FX-deficient patients.

CONCLUSIONS:

TGT may serve as a useful laboratory tool to assess the individual clinical manifestation of the patients with FX deficiency and 1 pM TF concentration in the presence of CTI is recommended.

• Authors: Qian Liang, Qiong Chen, Qiulan Ding, Fang Wu, Xuefeng Wang, Xiaodong Xi, Hongli Wang
• Journal: Thrombosis research (Thromb Res) Vol. 131 Issue 6 Pg. 554-9 (Jun 2013) ISSN: 1879-2472 [Electronic] United States
• PMID: 23664564 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Factor X
• Thromboplastin
• Thrombin

Topics

• Adult
• Aged
• Blood Coagulation Tests
• Factor X (genetics)
• Factor X Deficiency (blood, genetics, metabolism)
• Humans
• Infant
• Male
• Mutation, Missense
• Thrombin (metabolism)
• Thromboplastin (metabolism)