Abstract 1158

BACKGROUND

In 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.

METHODS

We 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.

RESULTS

We 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).

CONCLUSIONS

The 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 1.

Results of TPh testing

Total n(%)Before 2008 n(%)After 2008 n(%)*P value
Tested for TPh 881 (85.23) 578 (84.26) 303 (87.32) 0.22 
Any positive TPh 271 (26.23) 169 (24.64) 102 (29.39) 0.12 
Major TPh 95 (9.20) 60 (8.75) 35 (10.09) 0.56 
Anticardiolipin antibodies (IgG) 8 (0.77) 5 (0.73) 3 (0.86) >0.99 
Anticardiolipin antibodies (IgM) 20 (1.94) 14 (2.04) 6 (1.73) 0.92 
Lupus anticoagulant 22 (2.13) 18 (2.62) 4 (1.15) 0.19 
Any Antiphospholipid antibodies 49 (4.79) 38 (5.54) 11 (3.17) 0.12 
Protein S deficiency 17 (1.66) 5 (0.73) 12 (3.46) <0.01 
Protein C deficiency 16 (1.56) 9 (1.31) 7 (2.02) 0.96 
Antithrombin deficiency 6 (0.59) 3 (0.44) 3 (0.86) 0.65 
Positive APC Resistance 178 (17.40) 118 (17.20) 60 (17.29) 0.96 
Factor V Heterozygote 164 (16.03) 102 (14.87) 62 (17.87) 0.25 
Factor V Homozygote 5 (0.49) 4 (0.58) 1 (0.29) 0.91 
Prothrombin Heterozygote 41 (4.01) 23 (3.35) 18 (5.19) 0.21 
Prothrombin Homozygote 2 (0.20) 2 (0.29) 0 (0) 0.88 
Compound Heterozygote 4 (0.39) 2 (0.29) 2 (0.58) 0.84 
Total n(%)Before 2008 n(%)After 2008 n(%)*P value
Tested for TPh 881 (85.23) 578 (84.26) 303 (87.32) 0.22 
Any positive TPh 271 (26.23) 169 (24.64) 102 (29.39) 0.12 
Major TPh 95 (9.20) 60 (8.75) 35 (10.09) 0.56 
Anticardiolipin antibodies (IgG) 8 (0.77) 5 (0.73) 3 (0.86) >0.99 
Anticardiolipin antibodies (IgM) 20 (1.94) 14 (2.04) 6 (1.73) 0.92 
Lupus anticoagulant 22 (2.13) 18 (2.62) 4 (1.15) 0.19 
Any Antiphospholipid antibodies 49 (4.79) 38 (5.54) 11 (3.17) 0.12 
Protein S deficiency 17 (1.66) 5 (0.73) 12 (3.46) <0.01 
Protein C deficiency 16 (1.56) 9 (1.31) 7 (2.02) 0.96 
Antithrombin deficiency 6 (0.59) 3 (0.44) 3 (0.86) 0.65 
Positive APC Resistance 178 (17.40) 118 (17.20) 60 (17.29) 0.96 
Factor V Heterozygote 164 (16.03) 102 (14.87) 62 (17.87) 0.25 
Factor V Homozygote 5 (0.49) 4 (0.58) 1 (0.29) 0.91 
Prothrombin Heterozygote 41 (4.01) 23 (3.35) 18 (5.19) 0.21 
Prothrombin Homozygote 2 (0.20) 2 (0.29) 0 (0) 0.88 
Compound Heterozygote 4 (0.39) 2 (0.29) 2 (0.58) 0.84 
*

P for comparison before and after 2008.

Table 2.

Primary and secondary management outcomes

Reasons for continuing AC Beyond 6 MonthsTotal n(%)Before 2008 n(%)After 2008 n(%)*P-Value
All Patients 569 (55.08) 371 (54.08) 198 (57.06) 0.40 
Thrombophilia 139 (13.76) 95 (14.03) 44 (13.21) 0.80 
REVERSE Criteria 193 (25.63) 47 (10.78) 146 (46.06) <0.001 
Other Reasons 237 (22.94) 229 (33.38) 8 (2.31) <0.001 
Reasons for continuing AC Beyond 6 MonthsTotal n(%)Before 2008 n(%)After 2008 n(%)*P-Value
All Patients 569 (55.08) 371 (54.08) 198 (57.06) 0.40 
Thrombophilia 139 (13.76) 95 (14.03) 44 (13.21) 0.80 
REVERSE Criteria 193 (25.63) 47 (10.78) 146 (46.06) <0.001 
Other Reasons 237 (22.94) 229 (33.38) 8 (2.31) <0.001 
Disclosures:

Lazo-Langner:Pfizer: Honoraria; Leo Pharma: Honoraria.

Author notes

*

Asterisk with author names denotes non-ASH members.

Sign in via your Institution