The frequency of antithrombin deficiency (12% vs 0%), increased activated protein C (APC) resistance (32% vs 6%), total protein S deficiency (11% vs 1%) and elevated factor VIII:C activity (43% vs 17%) was significantly higher in female cases compared with controls.
Our results agree with the hypothesis that individuals with APC-resistance or protein S deficiency have an imbalance between pro- and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.
Three of fourteen children examined had abnormal normalized activated protein C sensitivity ratios.One child had protein S deficiency.The children had hyperlipidemia.
A 29-year-old female patient with heterozygous congenital protein S deficiency suffering from thrombotic disease had normal levels of both total and free protein S antigen (70% and 65%, respectively), but low cofactor activity (31%) for activated protein C, indicating that she had a variant of protein S, protein S Tokushima.
Protein S, a vitamin K-dependent coagulation factor, is involved in the regulation of the anticoagulant activity of activated protein C. Using an immunoradiometric assay for total protein S in plasma we identified 14 patients (7 male and 7 female) in three unrelated Dutch families as fulfilling the criteria for an isolated protein S deficiency.