Protein S活性檢驗的潛在限制與free protein S抗原方法可行性評估

Evaluation of potential limitations of protein S activity assay and feasibility of free protein S antigen assay

抗凝血蛋白protein S活性缺乏常見於台灣靜脈栓塞的病人中，因此protein S活性檢驗報告對於台灣人靜脈栓塞的診斷相當重要。Protein S活性檢驗的方法學是基於分析APC抗凝的活性的原理，屬於凝固法的一種，其靈敏度大於90%，但特異性只有40-70%。Protein S活性檢測特異性低的主要因素是檢測的原理易受生理變異及檢驗前的干擾所影響。本次實驗目的我們想驗證free protein S抗原分析方法導入實驗室的可行性，結果顯示在精密度、精確度、線性範圍及參考區間驗證均合格、且分析正常人其protein S活性與free protein S抗原表現，經統計後p值=0.11未達顯著差異，最後也證實了LA會干擾現行protein S活性的表現，經分析後現行protein S活性凝固法檢驗結果會相較於free protein S抗原檢驗結果偽性上升，平均為14.50%活性，且兩者檢驗結果其p值為<0.001達顯著差異。故顯示free protein S抗原不受免疫性抗體干擾，可以有較精準檢驗結果，因此建議臨床實驗室可建立free protein S抗原檢驗項目，來彌補protein S活性凝固法易受檢驗前的干擾。

Protein S activity deficiency is a common finding among patients with venous thromboembolism (VTE) in Taiwan, making protein S activity testing a critical tool for diagnosis. The clot-based protein S activity assays are designed to measure APC-dependent anticoagulant activity. The advantage of the protein S activity assay is to detect all clinical relevant hereditary defects (both qualitative and quantitative).The protein S activity assay has >90% sensitivity but the specificity is only 40-70%。The low specificity of Protein S activity assay is attributed to its clotting-based principle, which is susceptible to interference from biological and pre-analytical variables. This study aimed to assess the feasibility of introducing a free protein S antigen assay into routine diagnostics. Validation demonstrated acceptable accuracy, precision, linearity, and reference intervals. Comparisons in healthy individuals showed no significant difference between protein S activity and free protein S antigen levels (p = 0.11). Moreover, analysis revealed that lupus anticoagulant (LA) interfered with coagulation-based protein S activity assays, leading to pseudo-deficiency with an average overestimation of 14.5% and a significant difference between methods (p < 0.001). The free protein S antigen assay is not affected by immunologic interferences such as LA and provides more accurate results. Clinical laboratories are recommended to incorporate free protein S antigen testing to improve diagnostic accuracy in cases where protein S activity assays may be compromised.