Severe factor X deficiency in three unrelated Palestinian patients is caused by homozygosity for the mutation c302delG-correlation with thrombin generation and thromboelastometry.

Abstract

Factor X (FX) is one of the vitamin K-dependent serine proteases, which forms the prothrombinase complex converting prothrombin into thrombin. To search for mutations in F10 gene giving rise to severe FX deficiency and to study the contribution of thrombin generation and thromboelastometry as a tool for evaluation of hemostasis. Mutations in the F10 gene were sought by direct sequencing of all the eight exons and intron/exon boundaries. Thrombin generation and thromboelastometry were performed. Three unrelated Palestinian patients had undetectable FX level (<1 U/dl). All patients were found to be homozygous for c302delG, a new frameshift mutation in the F10 gene causing a stop codon at amino acid 73. The mutant allele was not detected among 152 Palestinians analyzed. Thrombin generation was examined in one of the patients 4 days after fresh frozen plasma was applied, when his FX level was 2 U/dl. Minute thrombin generation was observed, as compared to normal thrombin generation in heterozygotes for the mutation and a healthy control. Thromboelastometry revealed prolonged lag phase when patient's platelet-poor plasma and platelet-rich plasma were tested, with a slightly decreased initial clot formation rate, as compared to carriers' and control sample. Genetic analysis disclosed a unique mutation causing a severe phenotype. Thrombin generation assay may serve as a quick tool for confirming severe deficiency until the specific mutation is identified. Thrombin generation can also serve for monitoring and optimizing treatment. The correlation of thromboelastometry assay and severe FX deficiency is less striking.

• Authors: Tami Livnat, Boris Shenkman, Gili Kenet, Ilia Tamarin, Samuel Gillis, David Varon, Kenji Iijima, Ariella Zivelin, Ophira Salomon
• Journal: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis (Blood Coagul Fibrinolysis) Vol. 22 Issue 8 Pg. 673-9 (Dec 2011) ISSN: 1473-5733 [Electronic] England
• PMID: 22008904 (Publication Type: Journal Article)

Chemical References

• Factor X
• Thrombin

Topics

• Alleles
• Arabs
• Blood Coagulation
• Case-Control Studies
• DNA Mutational Analysis
• Exons
• Factor X (analysis, genetics)
• Factor X Deficiency (blood, diagnosis, ethnology, genetics)
• Frameshift Mutation
• Heterozygote
• Homozygote
• Humans
• Introns
• Israel (epidemiology)
• Pedigree
• Platelet-Rich Plasma (chemistry)
• Thrombelastography
• Thrombin (analysis, biosynthesis)
• Thrombin Time