ALBERT

Description: Venous thromboembolism (VTE) is a major therapeutic issue in cancer. Advances in this field and heterogeneities in clinical practices prompted us to establish guidelines related to VTE treatment and to central venous catheter thrombosis (CVCT) management. in cancer patients according to the SOR Standards, Options: Recommendations (SOR) methodology for the development of evidence-based Clinical Practice Guidelines (CPG) as endorsed by the French National Cancer Institute. Methods: After reviewing the published studies on the topics between 1999 and 2007, a first version of the guidelines was based on the levels of evidence derived from analysis of the 38 out of 418 selected studies for VTE treatment and the 40 out of 175 selected studies for the CVCT management. The recommendations were classified as Standards or Options and then peer-reviewed by 65 independent experts. Detailed methodology is available at www.sor-cancer.fr Standards in cancer patients: The treatment of VTE should be based on Low Molecular Weight Heparins (LMWH) at curative doses for at least 3 months. During the initial treatment (up to 10 days), there are no specific requirements and all drugs approved (including LMWH, Unfractionnated Heparin (UFH), fondaparinux and danaparoid) may be used. Beyond the first 10 days, VTE treatment should be based on LMWH at curative doses for at least 3 and optimally for 6 months, as validated with the following drugs and dosage regimens: dalteparin 200 IU/kg once daily for one month, then 150 IU/kg once daily; enoxaparin 150 IU/kg once daily; and tinzaparin 175 IU/kg once daily. In case of: severe renal impairment, UFH should be used rapidly followed by Vitamins K Antaogonist (VKA) for at least 3 months; severe Pulmonary Embolism (hemodynamic failure), the indications and usages of thrombolytic drugs are the same as in non-cancer patients; absolute contra-indication to anticoagulation or VTE recurrence despite optimal anticoagulation, vena cava filters (VCF) should be considered; intracranial malignancies, VTE treatment is the same as in cancer patients with non-intracranial tumors. CVCT treatment relies on long term use of LMWH. In case of severe renal failure, UFH with early AVK must be used. Treatment is to be continued as long as the catheter is maintained. This can only be achieved if the catheter is functional, well positioned, not infected and if adapted anticoagulation has resumed the CVCT. If catheter withdrawal is necessary, there is no standard concerning the anticoagulation management. CVCT prophylaxis relies on positioning the catheter distal extremity at the “superior vena cava - right atrium” junction. Systematic CVCT anticoagulant prophylaxis is not recommended. Options: Treatment of VTE: If LMWH administration for 3 months is impossible, short-term use of LWMH followed by VKA for at least 3 months may be proposed. It is recommended to administer LMWH for 3 to 6 months; LMWH should be used according to the same curative dosage regimen as during the first 3 months. Beyond the first 6 months, the anticoagulant treatment should be continued as long as the cancer is active or treated. In the event of a first VTE episode secondary to a transient risk factor and if the cancer is not active nor treated, anticoagulation may be discontinued after 6 months. The choice between LMWH and VKA depends on their benefit-risk ratio (influenced by drug interactions, chemotherapy, invasive procedures, and general health status) and acceptability. If a VCF is considered, a retrievable VCF may be discussed. CVCT treatment: If another catheter has to be inserted, prior evaluation of the venous circulation by scanner or ultrasound examination is recommended. If prolonged use of LMWH is impossible, VKA can be proposed. In case of severe superior vena cava syndrome, fibrinolytics can be used in the absence of contra-indications. Treatment by LMWH can be stopped 6 weeks after catheter withdrawal in non active cancer or after 3 to 6 months of LMWH followed by VKA in the other cases. CVCT prophylaxis: Right side catheter insertion and vein localisation by ultrasonography are preferred. Conclusion: The French recommendations further support the 2006 Italian and the 2007 North American guidelines on VTE treatment in cancer patients and were extended to the use of VCF and treatment of patients with intracranial malignancies. In addition, we provide recommendations on CVCT treatment in cancer patients.

Description: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common clinical problem, associated with a significant mortality and morbidity. Hence, accurate diagnosis and appropriate treatment are essential for patients presenting with suspected VTE. Unfortunately, the diagnosis of VTE is challenging in routine practice because of the nonspecific signs and symptoms of this disease. A large number of epidemiologic studies have focused on VTE, contributing to better understanding of this disease and improving its management. Demonstrated risk factors for VTE have been included into clinical prediction rules derived to help physician identify patients that should be referred for objective diagnostic tests. Over the past decade, the extensive use of diagnostic tests combined with the recent advances in imaging technology have resulted in more frequent diagnosis and treatment of early presentation of VTE, including isolated distal DVT or isolated PE. However the clinical signification of various VTE presentations remains unclear, and knowledge on epidemiology of VTE needs to be improve. Therefore we prospectively investigated the relative frequency and risk factors of isolated distal DVT, proximal DVT, PE with DVT and without DVT. Between November 2004 and January 2006, all patients over 18 years old who were referred to 359 french board certified vascular physicians for a clinical suspicion of VTE were included. VTE presentations were categorized using validated clinical decision rules and objective tests including ultrasonography, lung scan and helical CT scan. Subjects without an objectively confirmed diagnosis of VTE were used as controls. We performed multivariate analysis of risk factors for each type of VTE. 8256 patients entered the study, among which 7532 were analysed. The median age for all patients was 65 years (49–77 years), 2923 (39%) were men, 2925 were inpatients (39%), and 1884 (25%) had a previous history of VTE. 933 had isolated distal DVT (12%), 710 proximal DVT (9.4%), 426 PE with DVT (5.7%), 148 PE without DVT (2.0%) and 5315 had no VTE (70.6%). Classically risk factors were comparable for all different types of DVT (distal, proximal, or associated with PE). Curiously, risk factors for isolated pulmonary embolism are opposite to those for DVT-associated PE. Specially isolated PE was not associated with age (〉 75y, OR 1.2 [0.7–2.1, p 0.58), family history of VTE (OR 0.7 [0.4–1.3, p 0.26, bed confinement (OR 0.6[0.4–1.1, p 0.1),plaster (OR 0.3 [0.04–2.5, p 0.28), or acute respiratory or cardiac failure (OR 1.8 [0.9–3.3], p 0.07). Only personnal history of VTE (OR 1.7 [1.1–2.6], recent surgery (OR 1.7 [1.0–3.0], cancer [OR 1.7 [1.1–2.7, p 0.02) and contraceptive use (OR 6.3 [2.5–15.6] p〈 0.01) were shwon as risk factors for isolated PE. So this multicenter prospective cohort study shows heterogeneity in the risk factor profile between different forms of VTE encountered in daily practice, providing new insight in the epidemiology of this disease. Specifically, our study underlines the specific risk factors profile of isolated PE comparing to DVT-associated PE.

Description: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is associated with a significant mortality and life-long morbidity. A large number of studies have focused on VTE, contributing to better improving its management. Especially studies have provided accurate estimates of 3-month mortality rates for PE and have identified prognostic factors that may guide the physician’s initial treatment decision for these patients. However, improvements in the prevention of venous thromboembolism (VTE) and diagnosis have changed the epidemiology of VTE over the last twenty years. Advances in imaging technology have resulted in more frequent diagnosis and treatment of early presentation of VTE, including isolated distal DVT or isolated PE. However, the clinical signification and the prognosis of these forms of VTE are unknown. Therefore we prospectively investigated the 3-month overall for isolated distal DVT, proximal DVT, PE with DVT and PE without DVT, among a large in and out population study. Between November 2004 and January 2006, all patients over 18 years old who were referred to 359 french board-certified vascular physicians for a clinical suspicion of VTE were included. VTE presentations were categorized using validated clinical decision rules and objective tests including ultrasonography, lung scan and helical CT scan. Subjects without an objectively confirmed diagnosis of VTE were used as controls. All patients with confirmed VTE and a random sample of controls were followed-up at 3 months. We estimated 3 months survival for each type of VTE 8256 patients entered the study, among which 7532 were analysed. The median age for all patients was 65 years (49–77 years), 2923 (39%) were men, 2925 were inpatients (39%), and 1884 (25%) had a previous history of VTE. 933 had isolated distal DVT (12%), 710 proximal DVT (9.4%), 426 PE with DVT (5.7%), 148 PE without DVT (2.0%) and 5315 had no VTE (70.6%). Overall, 4290 patients were followed up at 3 months. At 3 months, VTE recurrence was not significantly different between the 5 groups of patients. By contrast, 95/2407 control patients (4%), 35/787 (4.4%) distal DVT, 48/598 (8%) proximal DVT, 48/371 (12.9%) PE with DVT, and 6/130 (4.6%) died. In multivariate analysis, the 3-months mortality adjusted hazard ratio [95% CI] was 1.1 [0.7–1.7] for distal DVT (P 0.59), 1.6 [1.1–2.3] for proximal DVT (P 0.013), 2.1 [1.4–3.0] for DVT-associated PE (p