Severe factor X deficiency in three unrelated Palestinian patients is caused by homozygosity for the mutation c302delG-correlation with thrombin generation and thromboelastometry.
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.
Institute of Thrombosis & Hemostasis Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Tami
T
Livnat
Boris
B
Shenkman
Gili
G
Kenet
Ilia
I
Tamarin
Samuel
S
Gillis
David
D
Varon
Kenji
K
Iijima
Ariella
A
Zivelin
Ophira
O
Salomon
D000483:Alleles; D018912:Arabs; D001777:Blood Coagulation; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005170:Factor X / Q000032:analysis / Q000235:genetics*; D005171:Factor X Deficiency / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D016368:Frameshift Mutation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007438:Introns; D007557:Israel / Q000453:epidemiology; D010375:Pedigree; D053657:Platelet-Rich Plasma / Q000737:chemistry; D013916:Thrombelastography; D013917:Thrombin / Q000032:analysis / Q000096:biosynthesis*; D013918:Thrombin Time
D005170:Factor X; D013917:Thrombin