S Schulman1,2, M Zondag1, L Linkins1, S Pasca3, Y W Cheung4, M de Sancho5, A Gallus6, R Lecumberri7, S Molnar8, W Ageno9, G Le Gal10, A Falanga11, E Hulegårdh12, S Ranta2, P Kamphuisen13, P Debourdeau14, V Rigamonti15, T L Ortel16, A Lee17. 1. Department of Medicine, McMaster University, Hamilton, ON, Canada. 2. Karolinska Institutet, Stockholm, Sweden. 3. Center for Hemorrhagic and Thrombotic Disease, University Hospital of Udine, Udine, Italy. 4. Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands. 5. Weill Cornell Medical College, New York, NY, USA. 6. Flinders University, Adelaide, SA, Australia. 7. Hematology Service, University Clinic of Navarra, Pamplona, Spain. 8. Oncology and Hematology Department, Sanatorio Allende, Cordoba, Argentina. 9. Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy. 10. Department of Internal Medicine and Chest Diseases, Brest University Hospital, Brest, France. 11. Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy. 12. Department of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden. 13. Department of Vascular Medicine, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. 14. Oncology Department, Ste Catherine Institute, Avignon, France. 15. Praxis Bubenberg, Bern, Switzerland. 16. Division of Hematology, Duke University Medical Center, Durham, NC, USA. 17. Diamond Health Care Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
Abstract
BACKGROUND: Recommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagulation strategies. METHODS: Patients with cancer and VTE despite anticoagulant therapy were reported to the registry. Data on treatments, VTE events, major bleeding, residual thrombosis symptoms and death were collected for the following 3 months. Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes with different treatment strategies were compared with Cox proportional hazards regression. RESULTS: We registered 212 patients with breakthrough VTE. Of those, 59% had adenocarcinoma and 73% had known metastases. At the time of the breakthrough event, 70% were on low-molecular-weight heparin (LMWH) and 27% on a vitamin K antagonist (VKA); 70% had a therapeutic or supratherapeutic dose. After breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased in 31%, switched to another drug in 24%; and other management in 11%. During the following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence was less common with LMWH than with a VKA (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.11-0.70) but similar with unchanged or increased anticoagulant intensity (HR, 1.09; 95% CI, 0.45-2.63). The bleeding rate did not increase significantly with dose escalation. CONCLUSION: Morbidity and mortality are high after recurrence of cancer-related VTE despite anticoagulation. Further treatment appears to be more effective with LMWH than with a VKA.
BACKGROUND: Recommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagulation strategies. METHODS:Patients with cancer and VTE despite anticoagulant therapy were reported to the registry. Data on treatments, VTE events, major bleeding, residual thrombosis symptoms and death were collected for the following 3 months. Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes with different treatment strategies were compared with Cox proportional hazards regression. RESULTS: We registered 212 patients with breakthrough VTE. Of those, 59% had adenocarcinoma and 73% had known metastases. At the time of the breakthrough event, 70% were on low-molecular-weight heparin (LMWH) and 27% on a vitamin K antagonist (VKA); 70% had a therapeutic or supratherapeutic dose. After breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased in 31%, switched to another drug in 24%; and other management in 11%. During the following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence was less common with LMWH than with a VKA (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.11-0.70) but similar with unchanged or increased anticoagulant intensity (HR, 1.09; 95% CI, 0.45-2.63). The bleeding rate did not increase significantly with dose escalation. CONCLUSION: Morbidity and mortality are high after recurrence of cancer-related VTE despite anticoagulation. Further treatment appears to be more effective with LMWH than with a VKA.
Authors: Michael B Streiff; Giancarlo Agnelli; Jean M Connors; Mark Crowther; Sabine Eichinger; Renato Lopes; Robert D McBane; Stephan Moll; Jack Ansell Journal: J Thromb Thrombolysis Date: 2016-01 Impact factor: 2.300
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