Clinical utility of thrombin generation using ST-Genesia® in patients with hereditary and acquired thrombophilia: A cross-sectional study
Lina Caspary a, Joseph R. Shaw b, Odile Stalder c, Justine Brodard a, Anne Angelillo-Scherrer a, Kristina Vrotniakaite-Bajerciene a b
a) Department of Hematology and Central Hematology Laboratory, Bern University Hospital, Bern, Switzerland
b) Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada
c) Department of Clinical Research, University of Bern, Bern, Switzerland
Abstract
Background
The role of thrombin generation (TG) in the setting of thrombophilia testing remains unclear. Hence, we aimed to investigate the diagnostic utility of TG with ST-Genesia® instrument to discriminate between patients with and without different thrombophilias.
Methods
We conducted a single-center cross-sectional study of all non-anticoagulated patients who underwent conventional thrombophilia testing for factor V Leiden, prothrombin gene G20210A mutation (PTM), protein C, S and antithrombin deficiency (PCD, PSD, ATD), and antiphospholipid antibody syndrome (APS) because of previous venous thromboembolism (VTE), unexplained arterial thrombosis or a positive family history for VTE. To assess the diagnostic utility of TG, we calculated the area under the receiver operating curve (AUC), thresholds for 85 %, 95 % and 99 % sensitivity and specificity, positive and negative predictive values and likelihood ratios, cohort-related diagnostic failure and efficacy rates and the diagnostic yield of each TG parameter for different thrombophilias.
Results
A total of 467 patients were enrolled in the study, mostly investigated because of previous VTE (n = 283, 61 %). Thrombophilia testing was positive in 161/467 (35 %) patients. Normalized endogenous thrombin potential (ETP) effectively discriminated for ATD (AUC =79 [95 %CI 72–87]) and PTM (AUC 86 [95 %CI 79–93]) and ETP inhibition with thrombomodulin for PCD/PSD (AUC 90 [95 %CI 85–95]). With the established best performing TG parameter cut-offs, PCD/PSD, PTM, ATD, and low-risk APS could be safely (<3 % failure rate) excluded in 62 %, 58 %, 27 %, and 29 % of cohort patients, respectively.
Conclusions
TG assessment using ST-Genesia® system shows promise as a supportive screening tool in thrombophilia work-up and warrants further validation.