title: Recurrent venous thromboembolism in anticoagulated patients with cancer: management and short-term prognosis.
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.
  
  
  CONCLUSIONS
  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: Department of Medicine, McMaster University, Hamilton, ON, Canada.|Karolinska Institutet, Stockholm, Sweden.
authors: S
authors: S
authors: Schulman
authors: Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors: M
authors: M
authors: Zondag
authors: Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors: L
authors: L
authors: Linkins
authors: Center for Hemorrhagic and Thrombotic Disease, University Hospital of Udine, Udine, Italy.
authors: S
authors: S
authors: Pasca
authors: Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
authors: Y W
authors: YW
authors: Cheung
authors: Weill Cornell Medical College, New York, NY, USA.
authors: M
authors: M
authors: de Sancho
authors: Flinders University, Adelaide, SA, Australia.
authors: A
authors: A
authors: Gallus
authors: Hematology Service, University Clinic of Navarra, Pamplona, Spain.
authors: R
authors: R
authors: Lecumberri
authors: Oncology and Hematology Department, Sanatorio Allende, Cordoba, Argentina.
authors: S
authors: S
authors: Molnar
authors: Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
authors: W
authors: W
authors: Ageno
authors: Department of Internal Medicine and Chest Diseases, Brest University Hospital, Brest, France.
authors: G
authors: http://orcid.org/0000-0002-9253-248X
authors: G
authors: Le Gal
authors: Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy.
authors: A
authors: A
authors: Falanga
authors: Department of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors: E
authors: E
authors: Hulegårdh
authors: Karolinska Institutet, Stockholm, Sweden.
authors: S
authors: S
authors: Ranta
authors: Department of Vascular Medicine, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
authors: P
authors: P
authors: Kamphuisen
authors: Oncology Department, Ste Catherine Institute, Avignon, France.
authors: P
authors: P
authors: Debourdeau
authors: Praxis Bubenberg, Bern, Switzerland.
authors: V
authors: V
authors: Rigamonti
authors: Division of Hematology, Duke University Medical Center, Durham, NC, USA.
authors: T L
authors: TL
authors: Ortel
authors: Diamond Health Care Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada.
authors: A
authors: A
authors: Lee
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D016009:Chi-Square Distribution; D057915:Drug Substitution; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000150:complications* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D014812:Vitamin K; D014859:Warfarin
keywords: bleeding; cancer; low-molecular-weight heparin; venous thromboembolism; warfarin