Abstract
Venous thromboembolism (VTE) is a multifactorial chronic disease. The number and severity of risk factors determine the risk of recurrence. A laboratory method that measures the overall thrombophilia is required.
In a prospective cohort study, we measured ETP in 778 patients with a first unprovoked VTE. Patients were followed after discontinuation of anticoagulants for an average of 49 months. The study endpoint was recurrent symptomatic VTE. ETP was determined by a commercially available (research use only) assay (Dade Behring, Marburg, Germany) in platelet poor plasma by use of a chromogenic substrate and automatic registration as well as computer assisted calculation of thrombin generation over time. Patients with recurrence had higher ETP than those without recurrence (104.2% ± 15.4% vs. 101.4% ±14.2%. Patients with ETP ≥ 100% had an almost two-fold higher relative risk (RR) of recurrence than patients with lower levels (RR 1.6, 95% CI 1.0 – 2.5). At 4 years, the cumulative probability of recurrence was 14.4% in patients with ETP ≥ 100% and 6.1% in those with lower levels (p = 0.05). Patients with ETP ≥ 100% had higher clotting factor levels (Table). ETP was significantly increased in heterozygous carriers of factor II G20210A as compared with patients with wild type factor II (128% ± 18% vs. 100 ± 12%, p < 0.001).
Patients with a first unprovoked VTE and an ETP ≥ 100% have an increased risk of recurrence.
. | ETP < 100% . | ETP ≥ 100% . | p-value . |
---|---|---|---|
Men, no. (%) | 160 (42%) | 174 (44%) | n.s. |
Age at first VTE (yrs) | 46 ± 17 | 47 ± 14 | n.s. |
Factor V Leiden, no. (%) | 124 (32%) | 108 (28%) | n.s. |
Factor II G20210A, no. (%) | 4 (1%) | 49 (13%) | < 0.001 |
Factor VIII (IU/dL) | 162 ± 46 | 168 ± 45 | 0.09 |
Factor IX (IU/dL) | 113 ± 24 | 123 ± 27 | < 0.001 |
Factor XI (IU/dL) | 102 ± 21 | 110 ± 24 | < 0.001 |
. | ETP < 100% . | ETP ≥ 100% . | p-value . |
---|---|---|---|
Men, no. (%) | 160 (42%) | 174 (44%) | n.s. |
Age at first VTE (yrs) | 46 ± 17 | 47 ± 14 | n.s. |
Factor V Leiden, no. (%) | 124 (32%) | 108 (28%) | n.s. |
Factor II G20210A, no. (%) | 4 (1%) | 49 (13%) | < 0.001 |
Factor VIII (IU/dL) | 162 ± 46 | 168 ± 45 | 0.09 |
Factor IX (IU/dL) | 113 ± 24 | 123 ± 27 | < 0.001 |
Factor XI (IU/dL) | 102 ± 21 | 110 ± 24 | < 0.001 |
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