Abstract 2299

Introduction:

The duration of anticoagulation after unprovoked venous thromboembolism (VTE) has been characterized as the most important unanswered question in clinical thrombosis management. This has led to research to identify predictors of recurrent VTE to identify high-risk patients who might warrant indefinite anticoagulation. Many clinicians assume that a family history of VTE is a predictor of recurrent VTE. This study aims to assess the value of family history as a predictor for recurrent VTE.

Methods:

Prospective multi-center multi-national cohort study recruited patients with a first objectively proven unprovoked VTE who completed 5 to 7 months of anticoagulation therapy. A detailed family history of VTE was completed for every subject. The information recorded included the number of affected relatives, whether they were first or second degree relatives and if the VTE was unprovoked or secondary. Patients were then followed for recurrent VTE.

Results:

664 subjects were enrolled between October 2001 and March 2006, 649 subjects were followed for a mean duration of 3.8 years (3.6–3.98 95% C.I.). The mean age of subjects in this cohort was 53 years (min-max 18–95) and 49% of subjects were females. A family history of VTE in at least 1 first-degree relative was recorded for 112 (17.3%) subjects. A total of 142 (21.9%) suspected VTE events were adjudicated as recurrences. The recurrence rate was 5.94% (4.89–7.15 95% C.I.) per patient-year for patients without any family history of VTE, and it was 4.82% (3.02–7.30 95% C.I.) per patient-year in patients with a family history of VTE in at least 1 first-degree relative. In secondary analyses, neither a family history of unprovoked VTE, multiple unprovoked VTE, in first-degree nor second-degree relatives was a predictor of recurrent VTE. A multivariate analysis was performed to adjust for known risk factors for VTE recurrence, but the adjusted hazard ratios were again not significantly different.

Conclusion:

A family history of VTE is not a predictor for recurrent VTE, and therefore should not be used to segregate unprovoked VTE patients in high- and low-risk categories.

Table 1.

Family history of venous thromboembolism (VTE), including first-degree relatives (FDR) and second-degree relatives (SDR), among patients with a single VTE and those with recurrent VTE.

Family HistoryPatients without recurrent VTE (n = 507)Patients with recurrent VTE (n = 142)Recurrence Rate per Patient-Year (%)Hazard Ratio (95% C.I.)Adjusted Hazard Ratio (95% C.I.) [1]
Negative      
No FDR or SDR with any type of VTE 390 112 5.94 (4.89–7.15) – – 
Positive      
Any relative (FDR&SDR) with any type of VTE 117 30 5.09 (3.43–7.26) 0.883 (0.590–1.322) 0.872 (0.569–1.337) 
Any relative (FDR&SDR) with an unprovoked VTE 66 15 4.82 (2.69–7.94) 0.827 (0.482–1.417) 0.799 (0.451–1.413) 
Two or more relatives (FDR&SDR) with any type of VTE 32 6 4.23 (1.55–9.21) 0.716 (0.315–1.628) 0.861 (0.374–1.981) 
Two or more relatives (FDR&SDR) with unprovoked VTE 13 2 4.18 (0.51–15.11) 0.677 (0.167–2.741) 0.860 (0.208–3.548) 
Family HistoryPatients without recurrent VTE (n = 507)Patients with recurrent VTE (n = 142)Recurrence Rate per Patient-Year (%)Hazard Ratio (95% C.I.)Adjusted Hazard Ratio (95% C.I.) [1]
Negative      
No FDR or SDR with any type of VTE 390 112 5.94 (4.89–7.15) – – 
Positive      
Any relative (FDR&SDR) with any type of VTE 117 30 5.09 (3.43–7.26) 0.883 (0.590–1.322) 0.872 (0.569–1.337) 
Any relative (FDR&SDR) with an unprovoked VTE 66 15 4.82 (2.69–7.94) 0.827 (0.482–1.417) 0.799 (0.451–1.413) 
Two or more relatives (FDR&SDR) with any type of VTE 32 6 4.23 (1.55–9.21) 0.716 (0.315–1.628) 0.861 (0.374–1.981) 
Two or more relatives (FDR&SDR) with unprovoked VTE 13 2 4.18 (0.51–15.11) 0.677 (0.167–2.741) 0.860 (0.208–3.548) 
[1]

Adjustment has been done for age, sex, BMI, factor V Leiden, prothrombin gene variant, HER (Hyperpigmentation, Edema and Redness), D-Dimer, hormone replacement therapy, oral contraceptives.

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Table 2.

Family history of venous thromboembolism (VTE), including first-degree relatives (FDR) only, among patients with a single VTE and those with recurrent VTE.

Family HistoryPatients without recurrent VTE (n = 507)Patients with recurrent VTE (n = 142)Recurrence Rate per Patient-Year (%)Hazard Ratio (95% C.I.)Adjusted Hazard Ratio (95% C.I.) [1]
Negative      
No first degree relative with any type of VTE 417 120 5.95 (4.93–7.11) – – 
Positive      
Any first degree relative with any type of VTE 90 22 4.82 (3.02–7.30) 0.844 (0.536–1.331) 0.859 (0.533–1.384) 
Any first degree relative with unprovoked VTE 49 12 5.18 (2.68–9.05) 0.883 (0.488–1.598) 0.875 (0.464–1.650) 
Family HistoryPatients without recurrent VTE (n = 507)Patients with recurrent VTE (n = 142)Recurrence Rate per Patient-Year (%)Hazard Ratio (95% C.I.)Adjusted Hazard Ratio (95% C.I.) [1]
Negative      
No first degree relative with any type of VTE 417 120 5.95 (4.93–7.11) – – 
Positive      
Any first degree relative with any type of VTE 90 22 4.82 (3.02–7.30) 0.844 (0.536–1.331) 0.859 (0.533–1.384) 
Any first degree relative with unprovoked VTE 49 12 5.18 (2.68–9.05) 0.883 (0.488–1.598) 0.875 (0.464–1.650) 
[1]

Adjustment has been done for age, sex, BMI, factor V Leiden, prothrombin gene variant, HER (Hyperpigmentation, Edema and Redness), D-Dimer, hormone replacement therapy, oral contraceptives.

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Disclosures:

No relevant conflicts of interest to declare.

Topics:
family history, oral contraceptives, venous thromboembolism, prospective studies, anticoagulation, edema, factor v leiden, fibrin fragment d substance, hormone replacement therapy, hyperpigmentation

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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