Hereditary deficiency of protein S (PS) or protein C (PC) are associated with increased risk of venous thrombosis, and the diagnosis is based on presence of low plasma levels. However, concentrations of PS and PC diminish during vitamin K antagonist therapy (VKA) [1,2] , and an exact diagnosis is therefore difficult to achieve during VKA therapy. Since patients with thromboembolism are likely to receive VKA therapy, it is nevertheless desirable to evaluate PS and PC during treatment, and despite general recommendations discourage investigation until VKA treatment is withdrawn [1,2] , it is unfortunately still a common procedure to draw samples during VKA therapy [3,4] . A recently published 9-month audit revealed that 144 of 194 cases (74.2 % ) with low levels of antithrombin, PS and PC appeared to be on anticoagulant therapy at the time of testing [4] . To solve this, it has previously been suggested to calculate a ratio between PS and PC to other vitamin K-dependent coagulation factors [5 -8] , which should enable determination of a reference interval for a normalized ratio independent of VKA treatment. However, the existing results are conflicting [9, 10] , and also, the utility of these ratios in clinical practice and in a larger population have not been described. Therefore, we aimed to investigate whether it is possible to establish a normalized ratio of PS or PC to coagulation factor II (FII) or X (FX) independent of the intensity of VKA treatment in a clinical setting.All patients referred between 2008 and 2011 for thrombophilia testing was eligible for the study. If patients were receiving Warfarin, FII and FX were also determined. Total PS antigen and PC antigen were only evaluated if initial measures of PS activity, free PS or PC activity were decreased. PS levels were determined with STA-STACLOT ® Protein S for activity, Protein S free STA-LIATEST ® and LIATEST ® Protein S for total PS antigen. PC was measured using Coamatic ® Protein C (Chromogenix Instrumentation Laboratory S.p.A, Italy) for activity and Vidas Protein C (BioM é rieux, France) for antigen measurement. Coagulation FII activity and FX activity were determined with STA-Neoplastine ® CI Plus with use of STA-deficient II or X as appropriate. The International Normalized Ratio (INR) was assessed with Stago Prothrombin-complex Assay (STA-SPA + ). All STA reagents as well as total PS assay were purchased from Diagnostica Stago, France. Values were considered low when below the laboratory reference range. Pair-wise correlation was calculated using Spearman ' s correlation test, and p-values < 0.05 were considered statistically significant. PASW statistics 18.0 was used for statistical analyses.A total of 1048 patients were eligible for the study. Measurement of PS was performed in 1039, while PC was measured in 1037. Low PS activity was detected in 134 patients of which 98 had an INR > 1.5; low free PS was detected in 89 patients (73 with INR > 1.5), while low PC activity was detected in 85 patients (80 with INR > 1.5). Concomitant low PS an...