[Vena cava filters and treatment of venous thromboembolism in cancer patients]

International audienceDespite numerous publications, there is still only one randomised clinical trial with vena cava filter in the treatment of venous thromboembolism (VTE). This study has shown a potential and early benefit on the risk of pulmonary embolism (PE) (the first three months) but a late negative effect on the risk of deep vein thrombosis (DVT) recurrences (beyond the sixth month) especially on the risk of filter thrombosis. Consequently, the international recommendations are against a systematic use of vena cava filter to treat VTE (grade 1A) and they suggest to use them in case of a recurrence despite adequate treatment or in case of a contra-indication to anticoagulants (grade 2C). But these two conditions are frequent with VTE associated with cancer since, the risk of VTE recurrences is about 5 to 10% despite prolonged low-molecular-weight heparins (LMWH) treatment and the major bleeding risk is also about 5 to 10% in this case. These VTE recurrences are frequently early (first month of treatment) and contra-indications to anticoagulants due to major bleeding are mostly temporary. In this way, retrievable vena cava filters (possible retrieval until six months after placement) could be useful in order, to prevent recurrences during the thromboembolic risk period without any prolonged increasing risk of vena cava thrombosis. However, vena cava filters could be associated with some complications (tilt, migration sepsis...). So without any strong validation, they have still to be considered as a therapeutic strategy needing to be evaluated especially in cancer patient

Heparin-associated thrombocytopenia in 24\u2003401 patients with venous thromboembolism: findings from the RIETE Registry1

BACKGROUND: Whether the treatment of venous thromboembolism (VTE) with unfractionated heparin (UFH) confers a higher risk of thrombocytopenia than does treatment with low molecular weight heparin (LMWH) remains controversial, and very few data are available from routine clinical practice. OBJECTIVES: We assessed the incidence, risk factors and prognosis of heparin-associated thrombocytopenia (HAT) according to the type of heparin therapy, UFH or LMWH. PATIENTS/METHODS: Data were obtained from the international prospective Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE), which included 25,369 patients with confirmed VTE until February 2009. Among them, 24,401 patients were treated either with UFH or with LMWH, and had available information about the 6-month occurrence of confirmed thrombocytopenia, defined as a platelet count 64 150,000 mm(-3) . RESULTS: One hundred and forty-one patients receiving UFH and/or LMWH developed thrombocytopenia within a 6-month period. The incidence of HAT was significantly higher in the UFH group (1.36%, 95% confidence interval [CI] 0.79-2.17) than in the LMWH group (0.54%, 95% CI 0.44-0.64). As compared with LMWH, UFH significantly increased the risk of HAT in female patients (adjusted hazard ratio [HR] 4.90%, 95% CI 2.58-9.31, P = 0.001) but not in male patients (adjusted HR 1.60%, 95% CI 0.64-3.97, P = 0.31); P = 0.027 for comparison. In each gender, the UFH-associated excess risk was confined to patients with VTE unrelated to cancer. The poor prognosis of patients with thrombocytopenia was not influenced by the type of heparin therapy. CONCLUSIONS: In routine clinical practice, treatment of VTE with UFH seems to confer a higher risk of thrombocytopenia than does treatment with LMWH, especially in women and non-cancerous patients

Lessons learned from cancer/VTE registries: Report from RIETE

International audienceThe general objective of this study was to proceed an inventory of measures which could help to improve the efficiency of clinical research in France. METHOD: Thanks to the discussion between the members of the round-table conference (composed of medical doctors (MD)/investigators; hospital managers; representatives of industrial promoters; general practitioners...), we have looked over the difficulties that meets clinical research in France nowadays. RESULTS: We identified four fields of action: 1) availability of resources for carrying out the trials in time and in quality; 2) feasibility of the clinical trials, in their design and for the recruitment which depends on both of the investigation centers and patients (what is the image of human testing in the society?); 3) skills and motivation of all the elements of staffs in charge of clinical trials (MD; nurses; and the new jobs in medical research); 4) promptness and efficiency of the administrative organisation for a fast starting up of the trials. CONCLUSION: This study, which doesn't pretend to sufficiency, shows the gap of improvement for French clinical trials organisation

Effects of age on the risk of dying from pulmonary embolism or bleeding during treatment of deep vein thrombosis

BACKGROUND: The risk of patients dying of pulmonary embolism (PE) or bleeding during the treatment of deep vein thrombosis (DVT), and whether these risks are influenced by patient age, has not been thoroughly studied. METHODS: We used data from the Registro Informatizado de la Enfermedad TromboEmb\uf3lica (RIETE) to assess the risk of fatal PE and fatal bleeding in 16,199 patients with lower limb DVT (without symptomatic PE at the time of inclusion) during the 3 months after diagnosis, with patients categorized according to age. RESULTS: During the 3 months of anticoagulant treatment, there were 31 fatal PEs (0.19%) and 83 fatal hemorrhages (0.51%). During the first 7 days of therapy, the frequency of fatal PEs was similar to that of fatal bleeding (12 vs 14 deaths, respectively; odds ratio [OR], 0.86; 95% confidence interval [CI], 0.39-1.87). However, from days 8 to 90, the frequency of fatal bleeding was greater than that of fatal PE (69 vs 19 deaths; OR, 3.64; 95% CI, 2.22-6.20). The higher frequency of fatal bleeding compared with fatal PE from days 8 to 90 appeared to be confined to patients who were aged 65 60 years. Multivariate analysis showed that patient age was independently associated with an increased risk of death from bleeding during the first 3 months: every 10 years the OR increased by 1.37 (95% CI, 1.12-1.67). CONCLUSIONS: During the first week of treatment, the risk of fatal bleeding and fatal PE were similar. Then, particularly in patients who were aged 65 60 years, the risk of dying from bleeding exceeded the risk of dying from PE

Usefulness of Thrombophilia Testing in Venous Thromboembolic Disease: Findings From the RIETE Registry

BACKGROUND: Information on thrombophilia risk factors for patients with upper extremity deep vein thrombosis (UEDVT) is limited. The genetic, acquired, and coagulation risk factors of an acute episode of lower EDVT (LEDVT) or UEDVT, either isolated or associated with pulmonary embolism (PE), were studied. MATERIALS AND METHODS: A total of 4503 patients participated in a thrombophilia study. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated. RESULTS: Mean age of the participants was 55 \ub1 19 years. The risk of LEDVT or UEDVT, isolated or associated with PE, was calculated according to thrombophilia factors. We found association between LEDVT and factor V Leiden ([FVL]; OR: 1.8; 95% CI 1.4-2.4) and resistance to activated protein C ([APC-R]; OR: 1.6; 95% CI 1.1-2.4). The LEDVT + PE presented an association with PTG20210A (OR: 1.5; 95% CI 1.1-2.1). No association was found between the thrombophilic defects studied and UEDVT or UEDVT + PE. CONCLUSIONS: Both FVL and APC-R carriers had the risk of developing LEDVT. The PTG20210A carriers had the risk of developing LEDVT + PE. No thrombophilic defects studied presented risk factors for UEDVT or UEDVT + PE

Long-term therapy with low-molecular-weight heparin in cancer patients with venous thromboembolism

Long-term therapy with low-molecular-weight heparin (LMWH) is the treatment of choice for cancer patients with venous thromboembolism (VTE). However, the ideal doses of LMWH have not been thoroughly studied. We used the RIETE Registry data to assess the influence of the daily LMWH dosage on outcome during the first three months after VTE. We used propensity score-matching to compare patients who received <150 vs. those receiving 65150 UI/kg/day LMWH. Up to July 2010, 3,222 cancer patients with VTE received long-term therapy with fixed doses of LMWH. Of these, 1,472 (46%) received <150 IU/kg/day (mean, 112 \ub1 28), and 1,750 received 65150 IU/kg/day (mean, 184 \ub1 32). Results of the propensity score matching involved 1269 matched pairs. During follow-up, the incidence of pulmonary embolism (PE) recurrences was similar (1.2% vs. 1.9%), but patients receiving <150 IU/kg/day LMWH had a lower incidence of fatal PE than those treated with 65150 IU/kg/day (0.2% vs. 1.0%; p=0.004). Multivariate analysis confirmed that patients receiving <150 IU/kg/day LMWH had a lower risk for fatal PE (odds ratio [OR]: 0.2; 95% confidence interval [CI]: 0.06-0.8) and for major bleeding (OR: 0.6; 95% CI: 0.3-1.0) than those treated with 65150 IU/kg/day. In real life, one in every two cancer patients with VTE received lower doses of LMWH than those used in randomised trials, with large variations from patient to patient. Unexpectedly, patients treated with <150 IU/kg/day LMWH had fewer fatal PE cases and fewer major bleeding events than those receiving 65150 IU/kg/day LMWH. This finding, however, should be validated in prospective clinical trials