Thrombophilia, Clinical Factors, and Recurrent Venous Thrombotic Events

Abstract

Context Data on the recurrence rate of venous thrombotic events and the effect of several risk factors, including thrombophilia, remain controversial. The potential benefit of screening for thrombophilia with respect to prophylactic strategies and duration of anticoagulant treatment is not yet known. Objectives To estimate the recurrence rate of thrombotic events in patients after a first thrombotic event and its determinants, including thrombophilic abnormalities. Design, Setting, and Patients Prospective follow-up study of 474 consecutive patients aged 18 to 70 years without a known malignancy treated for a first objectively confirmed thrombotic event at anticoagulation clinics in the Netherlands. The Leiden Thrombophilia Study (LETS) was conducted from 1988 through 1992 and patients were followed up through 2000. Main Outcome Measures Recurrent thrombotic event based on thrombophilic risk factors, sex, type of initial thrombotic event (idiopathic or provoked), oral contraceptive use, elevated levels of factors VIII, IX, XI, fibrinogen, homocysteine, and anticoagulant deficiencies. Results A total of 474 patients were followed up for mean (SD) of 7.3 (2.7) years and complete follow-up was achieved in 447 (94%). Recurrence of thrombotic events occurred in 90 patients during a total of 3477 patient-years. The rate of thrombotic event recurrence was 25.9 per 1000 patient-years (95% confidence interval [CI], 20.8-31.8 per 1000 patient-years). The incidence rate of recurrence was highest during the first 2 years (31.9 per 1000 patient-years; 95% CI, 20.3-43.5 per 1000 patient-years). The risk of thrombotic event recurrence was 2.7 times (95% CI, 1.8-4.2 times) higher in men than in women. Patients whose initial thrombotic event was idiopathic had a higher risk of a thrombotic event recurrence than patients whose initial event was provoked (hazard ratio [HR], 1.9; 95% CI, 1.2-2.9). Women who used oral contraceptives during follow-up had a higher thrombotic event recurrence rate (28.0 per 1000 patient-years; 95% CI, 15.9-49.4 per 1000 patient-years) than those who did not (12.9 per 1000 patient-years; 95% CI, 7.9-21.2 per 1000 patient-years). Recurrence risks of a thrombotic event by laboratory abnormality ranged from an HR of 0.6 (95% CI, 0.3-1.1) in patients with elevated levels of factor XI to an HR of 1.8 (95% CI, 0.9-3.7) for patients with anticoagulant deficiencies. Conclusions Prothrombotic abnormalities do not appear to play an important role in the risk of a recurrent thrombotic event. Testing for prothrombotic defects has little consequence with respect to prophylactic strategies. Clinical factors are probably more important than laboratory abnormalities in determining the duration of anticoagulation therapy.

Long-term clinical and ultrasonographic evaluation of thrombophilic patients with deep venous thrombosis

“…The frequency of APS in our patients was higher than is reported in the literature (4-14%). 17,29,30 We have no explanation for this high frequency, which seems to be real, since we used the Sapporo Criteria to diagnose our cases 31 and antibodies remained high 60 days after the first assays. On the other hand, our results are similar to the literature in relation to FV Leiden, which is the most common genetic condition linked with DVT, groups in terms of any of the following variables: ethnicity, urban or rural origin, profession, number of pregnancies after DVT or number miscarriages after DVT.…”

Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen γ′ levels

“…38 Separate analyses were performed for patients with (n ϭ 259) and without (n ϭ 215) idiopathic thrombosis, in whom idiopathic was defined as an initial thrombotic event that occurred in the absence of pregnancy, puerperium, oral contraceptive use within 30 days, trauma, surgery, immobilization, or use of a plaster cast within 3 months before the event. 39 …”

Inherited Risk Factors for Venous Thrombosis

“…The LETS group reported on a broad array of thrombophilic risk factors with 7.3-years of follow-up of 474 patients younger than age 70 with a first DVT. 24 Considering levels of factors VIII, IX, XI, fibrinogen, homocysteine, anticoagulant factor deficiencies (proteins C, S and antithrombin), factor V Leiden and prothrombin 20210A, only elevated fibrinogen (> 4.1 g/L) and anticoagulant deficiencies were associated with an elevated recurrence risk (relative risks 1.7 and 1.8, respectively). It is debatable whether elevated fibrinogen is a risk factor for first VT. 25 In a recent 5.6 year study of families with thrombosis attributed to factor V Leiden or deficiencies of anticoagulant proteins, antithrombin deficiency was associated with the highest incidence of recurrent VT (10.5% yearly), and factor V Leiden the lowest incidence (3.5% yearly).…”

“…In fact, it is believed that patients with more than one identifiable thrombophilic defect are at increased recurrence risk compared to those with no or one defect. 24 Other data suggest that higher D-dimer concentration after discontinuing anticoagulation is associated with about a 2-fold increased risk of recurrent VT, 27,28 although confirmation of this is required and the definition of high D-dimer needs clarification.…”