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.