Normal levels of protein C and protein S tested in the acute phase of a venous thromboembolic event are not falsely elevated

BACKGROUND: Protein C (PC) and protein S (PS) determination is part of the thrombophilia investigation in patients with idiopathic venous thromboembolism (VTE). Based on scarce evidence it is a common notion that PC and PS levels decrease during the acute phase of VTE, necessitating delay of testing and temporary transition from warfarin to low molecular weight heparin. We have previously demonstrated that an abnormal PC or PS result determined within 24 hours of VTE diagnosis and before the initiation of warfarin needs to be repeated for confirmation ≥3 months after starting treatment and ≥14 days after stopping anticoagulation therapy. In the current study, we sought to show that normal PC and PS values determined during the acute phase of VTE are not false negatives. METHODS: 99 patients with acute idiopathic VTE who had normal PC and PS determination within the first 24 hours of presentation and who subsequently had their oral anticoagulation discontinued after six months of therapy. PC and PS determinations were repeated ≥6 months after starting treatment and ≥ 14 days after stopping warfarin. Proportions of patients who tested abnormal on the second test were calculated and 95% confidence intervals obtained using the Wilson's score method. Data from a previously published study on patients with abnormal initial tests was included for comparison. RESULTS: None of the 99 patients who had normal PC and PS initially had an abnormal result on repeated testing (0%; 95% CI 0 - 3.7%). Data from the previous study showed that, among patients who initially had abnormal results, 40% (95%CI 35.4-84.8%) were confirmed to have low PC and 63.6% (95%CI 16.8-68.7%) low PS on repeated testing. The difference between proportions was statistically significant (χ(2 )p-value < 0.001). CONCLUSION: Our results suggest that PC and PS can be determined during the acute phase of VTE and whereas abnormal results need to be confirmed with repeat testing at a later date, a normal result effectively rules out deficiency with only one test.