Clinical characteristics of patients with factor V Leiden or prothrombin G20210A and a first episode of venous thromboembolism. Findings from the RIETE Registry.

BACKGROUND: The clinical characteristics of patients with factor V Leiden or prothrombin G20210A presenting with a first episode of venous thromboembolism (VTE) have not been thoroughly studied. METHODS: RIETE is an ongoing registry of consecutive patients with acute VTE. We compared the clinical characteristics of patients with factor V Leiden, prothrombin G20210A, or no thrombophilia, at presentation with a first episode of VTE. RESULTS: As of May 2009, 22428 patients had been enrolled with a first episode of VTE. Of these, 345 had factor V Leiden, 261 had prothrombin G20210A, and 2399 tested negative. Sixty-two percent of the VTE episodes in women with factor V Leiden or prothrombin G20210A (40% in men) were associated with an acquired risk factor. Among women, pregnancy or contraceptive use accounted for 63% and 67% of such risk factors. Patients with factor V Leiden presented with pulmonary embolism (PE) less likely than those with prothrombin G20210A (31% vs. 51%; p<0.001) or with negative testing (31% vs. 45%, p<0.001). In addition, PE patients with Factor V Leiden presented with hypoxaemia (Sat O(2) levels<90%) less likely than those with prothrombin G20210A (4.5% vs. 17%; p<0.001) or with no thrombophilia (4.5% vs. 20%; p<0.001). CONCLUSIONS: Most VTE episodes in women (not men) with factor V Leiden or prothrombin G20210A were associated with an acquired risk factor (mostly pregnancy or contraceptive use). Only 4.5% of patients with factor V Leiden presenting with acute PE had hypoxaemia.

Clinical outcome of patients with upper-extremity deep vein thrombosis: results from the RIETE Registry.

BACKGROUND: There is little information on the clinical outcome of patients with upper-extremity deep vein thrombosis (DVT). METHODS: RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute DVT or pulmonary embolism (PE). In this analysis, we analyzed the demographic characteristics, treatment, and 3-month outcome of all patients with DVT in the arm. RESULTS: Of the 11,564 DVT patients enrolled, 512 patients (4.4%) had arm DVT. They presented less often with clinically overt PE (9.0% vs 29%; odds ratio, 0.24; 95% confidence interval [CI], 0.18 to 0.33) than those with lower-limb DVT, but their 3-month outcome was similar. Of the 512 patients with arm DVT, 196 patients (38%) had cancer and 228 patients (45%) had catheter-related DVT. During follow-up, those with cancer DVT had an increased incidence of major bleeding (4.1% vs 0.9%; odds ratio, 4.4; 95% CI, 1.2 to 21), recurrent venous thromboembolism (6.1% vs 2.8%; odds ratio, 2.2; 95% CI, 0.91 to 5.6; p = 0.04), and death (22% vs 3.5%; odds ratio, 7.8; 95% CI, 4.0 to 16). Thirty patients had the composite event of recurrent DVT, symptomatic PE, or major bleeding. They were significantly older, more often had cancer, and presented more frequently with symptomatic PE on hospital admission. On multivariate analysis, only cancer patients with arm DVT had an increased risk for the composite event (odds ratio, 3.0; 95% CI, 1.4 to 6.4). CONCLUSIONS: At presentation, patients with arm DVT have less often clinically overt PE than those with lower-limb DVT, but their 3-month outcome is similar. Among patients with arm DVT, those with cancer have the worse outcome.

Incidence of chronic thromboembolic pulmonary hypertension after a first episode of pulmonary embolism.

STUDY OBJECTIVE: To assess the incidence of chronic thromboembolic pulmonary hypertension (CTPH) after the first episode of objectively confirmed pulmonary embolism (PE). DESIGN: Prospective cohort study in 12 Italian medical centers. PATIENTS: Consecutive patients treated with oral anticoagulants for the first episode of PE, either idiopathic or associated with temporary risk factors, were followed up for at least 3 years. Patients were excluded from the study if they had a known persistent risk factor for venous thromboembolism (VTE). INTERVENTIONS: At the follow-up visits, patients were evaluated for persistent dyspnea, either at rest or on exertion. All patients who were referred with dyspnea were assessed by transthoracic echocardiography, with evaluation of the systolic and mean pulmonary artery pressures. Patients with evidence of pulmonary hypertension on echocardiography underwent perfusion lung scans and pulmonary angiography to confirm the diagnosis of CTPH. RESULTS: Overall, 259 patients were included in the study. PE was idiopathic in 135 patients, while it was associated with at least a temporary risk factor for VTE in 124 patients. After an average follow-up period of 46 months, 37 patients were found to have persistent dyspnea that was unexplained in 5 patients. Among these patients, a diagnosis of CTPH was confirmed in two patients with idiopathic PE (0.8% of the overall study population [95% confidence interval (CI), 0.0 to 1.9]; 1.5% of patients with idiopathic PE [95% CI, 0.0 to 3.6]). The diagnosis was made 14 and 22 months, respectively, after the acute PE. CONCLUSIONS: The incidence of CTPH observed in this study was about 1%. CTPH was observed in two patients with idiopathic PE.

A prospective study on cardiovascular events after acute pulmonary embolism.

AIMS: To evaluate the incidence of cardiovascular events in the long-term clinical course of patients with a first episode of symptomatic, objectively confirmed pulmonary embolism. METHODS AND RESULTS: Three hundred and sixty patients with a first episode of pulmonary embolism were included in a prospective study: 209 with idiopathic pulmonary embolism and 151 with pulmonary embolism associated with transient risk factors. The study outcomes were cardiovascular events (recurrent venous thrombo-embolism, acute myocardial infarction, stroke, sudden otherwise unexplained death), cardiovascular death, and death due to any cause. The median follow-up was 38 months. Sixty-four patients had at least one cardiovascular event (5.5% patient-year). Recurrent venous thrombo-embolism occurred in 45 patients (3.9% patient-year), acute myocardial infarction in 12 patients (1.0% patient-year), stroke in six patients (0.5% patient-year), and sudden otherwise unexplained death in four patients (0.3% patient-year). A cardiovascular event occurred in 47 patients with idiopathic pulmonary embolism (7.5% patient-year) and in 17 patients with pulmonary embolism associated with transient risk factors (3.1% patient-year) (RR 2.0; 95% CI 1.20-3.34; P=0.006). Twenty patients with idiopathic pulmonary embolism (3.2% patient-year) and two patients with pulmonary embolism associated with transient risk factors (0.4% patient-year) presented an arterial cardiovascular event (RR 7.2; 95% CI 1.71-30.45; P=0.001). Thirty-three patients died (9.2%). Cardiovascular mortality and cancer mortality accounted for 42.4 and 21.2% of overall mortality, respectively. Idiopathic pulmonary embolism was an independent predictor of cardiovascular events after adjusting for age. CONCLUSIONS: Cardiovascular events are more common in patients with idiopathic pulmonary embolism than in patients with pulmonary embolism associated with transient risk factors. Cardiovascular events are the major cause of death in patients with idiopathic pulmonary embolism.

Extended oral anticoagulant therapy after a first episode of pulmonary embolism.

BACKGROUND: The optimal duration of oral anticoagulant treatment after a first episode of pulmonary embolism remains uncertain. OBJECTIVE: To evaluate the long-term clinical benefit of extending a 3-month course of oral anticoagulant therapy to 6 months (pulmonary embolism associated with temporary risk factors) or to 1 year (idiopathic pulmonary embolism) in patients with a first episode of pulmonary embolism. DESIGN: Multicenter randomized study with independent, blinded assessment of the outcome events. SETTING: 19 Italian hospitals. PATIENTS: 326 patients who had had 3 months of oral anticoagulant therapy without experiencing recurrence or bleeding. MEASUREMENTS: The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism. RESULTS: Among 165 patients assigned to extended anticoagulant therapy, 15 patients (9.1%) had a recurrence of venous thromboembolism (3.1% per patient-year; average follow-up, 34.9 months), as compared with 18 of 161 patients (11.2%) assigned to discontinue treatment (4.1% per patient-year; average follow-up, 32.7 months); the rate ratio was 0.81 (95% CI, 0.42 to 1.56). All but one of the recurrences occurred after anticoagulant treatment was discontinued. Nineteen recurrences (57.6%) were episodes of pulmonary embolism, two of which were fatal. Three major bleeding episodes were observed during extended anticoagulation (1.8%). Among patients with idiopathic venous thromboembolism, 11 of 90 patients assigned to extended anticoagulation and 11 of 91 patients assigned to discontinue treatment experienced a recurrence (relative risk, 0.99 [CI, 0.45 to 2.16]). CONCLUSION: Patients with pulmonary embolism have a substantial risk for recurrence after discontinuation of oral anticoagulation, regardless of treatment duration. Physicians should try to identify patients who are at high risk for recurrent venous thromboembolism and are therefore potential candidates for indefinite oral anticoagulant therapy.