New quantitative total protein S-assay system for diagnosing protein S type II deficiency: clinical application of the screening system for protein S type II deficiency.

Abstract

Venous thromboembolism (VTE) incidence is rising rapidly in Japan with lifestyle westernization and aging. Deficiency of protein S, an important blood coagulation regulator, is a risk factor for VTE. Protein S deficiency prevalence in Asians is approximately 10 times that in Caucasians and that of protein S type II deficiency, associated with the protein S Tokushima mutation (K155E), is quite high in Japan. However, currently available methods for measuring protein S are not precise enough for detection of this deficiency. We developed a novel assay system for precise simultaneous determinations of total protein S activity and total protein S antigen level, using a general-purpose automated analyzer, allowing protein S-specific activity (ratio of total protein S activity to total protein S antigen level) to be calculated. Mean specific activity was 0.99 for samples from healthy individuals but 0.69 or less (mean-3SD) in protein S type II-deficient and warfarin-treated samples, but was 1.0 in an estrogen-treated sample with significantly decreased protein S antigen. Protein S gene analyses in healthy individuals with specific activity 0.69 or less revealed the K155E mutation in all three. These results show our new assay system to be an effective screening tool for protein S type II deficiency. This system can also be used in an automated analyzer, facilitating numerous sample measurements, and is, thus, applicable to regular medical checkups and diagnosing VTE. Such applications would potentially contribute to early detection of protein S type II deficiency, and, thereby, to thrombosis prevention.

• Authors: Tomohide Tsuda, Xiuri Jin, Hiroko Tsuda, Masahiro Ieko, Eriko Morishita, Tomoko Adachi, Naotaka Hamasaki
• Journal: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis (Blood Coagul Fibrinolysis) Vol. 23 Issue 1 Pg. 56-63 (Jan 2012) ISSN: 1473-5733 [Electronic] England
• PMID: 22157257 (Publication Type: Journal Article)

Chemical References

• Protein S

Topics

• Case-Control Studies
• Colorimetry (methods)
• Female
• Humans
• Incidence
• Male
• Mass Screening
• Protein S (analysis)
• Protein S Deficiency (blood, diagnosis)
• Risk Factors
• Sensitivity and Specificity
• Venous Thrombosis (blood)