Methods
Study design and patients: This was a single center retrospective longitudinal study of patients with a confirmed VTE and undergoing IT testing between January 2011 and December 2016. An initial database of all patients who have been referred to the hematology laboratory from the internal medicine department during this period for constitutional thrombophilia testing has been established. Clinical data were obtained from medical records using a standardized form and included the following: demographic characteristics, cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidimia, obesity, smoking), bleeding risk factors (renal or liver impairment, antiplatelet drugs), history of cardiovascular or venous thrombotic event, adverse pregnancy outcome, details of index VTE defined as the thrombotic event which had indicated thrombophilia screening (localization, provoked/unprovoked VTE [9]), indication and timing of testing, anticoagulation duration), details of recurrent VTE, other complications (bleeding events or postphlebitic syndrome). Patients from other departments were not included. Those with missing clinical data were excluded.
Thrombophilia screening: Laboratory investigation focused on screening for AT, PC, PS protein C deficiencies and activated protein C resistance (aPCR). Unfortunately, results from factor V Leiden and prothrombin gene mutation were not available. Laboratory tests were performed on automate type STA Compact Max using reagents from STAGO (STACHROM AT, STACLOT PC, STACLOT PS and STACLOT-APCR). The presence of IT was considered only if repeated tests showed persistently abnormal results (AT<80%, PC<70%, PS<55% or APCR<120 seconds) and/or if the abnormal defect was also shown in family investigation.
Ethical considerations: All patient data were anonymized prior to analysis. This study was approved by the local ethics committee.
End points: Decision to pursuit or discontinue anticoagulation and occurence of recurrent thrombotic events
Statistical analysis: Qualitative variables were expressed as percentages and frequencies. Quantitative variables were expressed as means. Comparisons of qualitative variables were tested by χ2 or Fisher test, as appropriate. Comparisons of quantitative variables were performed with T Student test. The recurrence-free survival analysis was done by Kaplan Meier method: The log-Rank test was used to compare two curves of survival without recurrence. The Hazard recurrence ratios were carried out using a COX model. The time scale used in the two statistical survival tests (the Kaplan Meier method and the COX model) was the time between the index VTE (model A) or the anticoagulation withdrawal (model B) and the recurrent event/the end of the follow up or the end of the study. A p value <0.05 was considered as statistically significant. All statistical analysis were performed using SPSS 20.0 Software.