Impact of Thrombophilia Screening On Venous Thromboembolism Management Practices

Abstract

AbstractAbstract 1158 BACKGROUNDIn patients with idiopathic venous thromboembolism (VTE) thrombophilia screening (TS) is usually done with the aim of helping to guide long term management. Since 2008 our center has modified clinical practice and decisions on long term management have been based on the findings of the REVERSE study (Rodger et al., CMAJ 2008), which stratifies recurrence risk based on clinical and laboratory risk factors excluding thrombophilia (TPh). We therefore aimed to study the current impact of TS on VTE management practices, particularly since the advent of the REVERSE study. METHODSWe conducted a single-center, retrospective cohort study of all patients with objectively confirmed VTE who were consecutively referred to our thrombosis clinic from January 1st, 1999 to December 31st 2011. Patients were excluded if the VTE was due to hospital stay, pregnancy, immobility, or surgery. The primary outcome was the decision of maintaining anticoagulation (AC) beyond the initial planned period (6 months after VTE) based on TS. Secondary outcomes included decision of maintaining AC based on REVERSE criteria or other reasons, and incidence of recurrent VTE. Major TPh was defined as any of: confirmed antithrombin, protein S or protein C deficiencies, persistently positive anticardiolipin antibodies or lupus anticoagulant, or homozygote/compound heterozygote carriers of the Factor V Leiden or G20210A prothrombin gene variant. According to the year of diagnosis patients were divided in groups before and after 2008. Groups were compared using χ2 or Fisher’s exact tests, as appropriate. Survival data was analyzed using the Kaplan-Meier method and Cox regression analysis. RESULTSWe included 1033 out of 1100 eligible patients. Mean age was 55.59 years (SD 17.96), the mean length of follow up was 55.5 months (range 0 to 229), and 48.11% were female. Of 880 (85.2%) known family histories, 12.39% were positive for a previous VTE. Results for TPh testing and primary and secondary outcomes are shown in Tables 1 and 2. Overall, the proportion of patients continuing AC based on TS was small. After 2008, the majority of patients continuing OAT were based on REVERSE criteria. Compared to patients without TPh and after adjusting for AC continuation beyond 6 months, the presence of non-major TPh resulted in a modest increase in VTE recurrence risk (OR 1.71, 95% CI 1.20–2.44; P<0.01) whereas the presence of major TPh did not (OR 0.55, 95% CI 0.19–2.44; P=0.27). Continuation of AC beyond the initial planned period resulted in 75% reduction in VTE recurrence risk (OR 0.25, 95%CI 0.12–0.55; P<0.001). CONCLUSIONSThe impact of TPh on VTE recurrence is small and the proportion of patients in whom TS results in long term AC is low. Furthermore, current decisions of AC duration are based on clinical criteria and might impact the risk of VTE recurrence to a greater extent than TS. Although at present TS seems to have a less preponderant role in management decisions, it might be of value for counseling purposes.Table 1Results of TPh testingTotal n(%)Before 2008 n(%)After 2008 n(%)*P valueTested for TPh881 (85.23)578 (84.26)303 (87.32)0.22Any positive TPh271 (26.23)169 (24.64)102 (29.39)0.12Major TPh95 (9.20)60 (8.75)35 (10.09)0.56Anticardiolipin antibodies (IgG)8 (0.77)5 (0.73)3 (0.86)>0.99Anticardiolipin antibodies (IgM)20 (1.94)14 (2.04)6 (1.73)0.92Lupus anticoagulant22 (2.13)18 (2.62)4 (1.15)0.19Any Antiphospholipid antibodies49 (4.79)38 (5.54)11 (3.17)0.12Protein S deficiency17 (1.66)5 (0.73)12 (3.46)<0.01Protein C deficiency16 (1.56)9 (1.31)7 (2.02)0.96Antithrombin deficiency6 (0.59)3 (0.44)3 (0.86)0.65Positive APC Resistance178 (17.40)118 (17.20)60 (17.29)0.96Factor V Heterozygote164 (16.03)102 (14.87)62 (17.87)0.25Factor V Homozygote5 (0.49)4 (0.58)1 (0.29)0.91Prothrombin Heterozygote41 (4.01)23 (3.35)18 (5.19)0.21Prothrombin Homozygote2 (0.20)2 (0.29)0 (0)0.88Compound Heterozygote4 (0.39)2 (0.29)2 (0.58)0.84*P for comparison before and after 2008.Table 2Primary and secondary management outcomesReasons for continuing AC Beyond 6 MonthsTotal n(%)Before 2008 n(%)After 2008 n(%)*P-ValueAll Patients569 (55.08)371 (54.08)198 (57.06)0.40Thrombophilia139 (13.76)95 (14.03)44 (13.21)0.80REVERSE Criteria193 (25.63)47 (10.78)146 (46.06)<0.001Other Reasons237 (22.94)229 (33.38)8 (2.31)<0.001 Disclosures:Lazo-Langner:Pfizer: Honoraria; Leo Pharma: Honoraria.