Genetic analysis for women with protein S deficiency

Abstract

Introduction: Serum levels of protein S (PS) can be affected by various factors. During pregnancy, estrogen naturally decreases serum PS levels, and it is difficult to evaluate pathological significance for low levels of PS. The genetic analysis of PS deficiency may help the evaluation. Patients andmethod: Between October 2010 and June 2014, serum levels of PS were measured for 299 women having a history of thrombosis and/or recurrent pregnancy loss (RPL). Seventy-six (25.4%)womenhad lowPSactivities. Thegenetic analysis of PSwasperformed in31womenwith low PS activities with approval of the Institutional Ethics Board and informed consent. The 31 women consisted of 21 women with RPL and 10 with thrombosis. Results: Serum PS levels of 31 were median 40.5%, ranging from 27 to 60%. Five (16.1%) women including 4 women with RPL and 1 with thrombosis had PS gene missense mutations (Tokushima mutation, Lys196Glu; n=4; Val86Leu n=1). Serum PS levels of women with wild type and women with mutations were median 41% (36–60%) and 33% (27–53%), respectively (no statistically significant difference, p=0.56). Two pregnancies of women with PS gene mutations receiving heparin therapies ended in full term deliveries, and the other 2 pregnancies are on going. Conclusion: The genetic analysis of PS deficiencymight be useful to select therapeutic modality for pregnant women with a history of RPL or thrombosis.