title: International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer.
abstract: BACKGROUND
  Guidelines addressing the management of venous thromboembolism (VTE) in cancer patients are heterogeneous and their implementation has been suboptimal worldwide.
  
  
  OBJECTIVE
  To establish a common international consensus addressing practical, clinically relevant questions in this setting.
  
  
  METHODS
  An international consensus working group of experts was set up to develop guidelines according to an evidence-based medicine approach, using the GRADE system.
  
  
  RESULTS
  For the initial treatment of established VTE: low-molecular-weight heparin (LMWH) is recommended [1B]; fondaparinux and unfractionated heparin (UFH) can be also used [2D]; thrombolysis may only be considered on a case-by-case basis [Best clinical practice (Guidance)]; vena cava filters (VCF) may be considered if contraindication to anticoagulation or pulmonary embolism recurrence under optimal anticoagulation; periodic reassessment of contraindications to anticoagulation is recommended and anticoagulation should be resumed when safe; VCF are not recommended for primary VTE prophylaxis in cancer patients [Guidance]. For the early maintenance (10 days to 3 months) and long-term (beyond 3 months) treatment of established VTE, LMWH for a minimum of 3 months is preferred over vitamin K antagonists (VKA) [1A]; idraparinux is not recommended [2C]; after 3-6 months, LMWH or VKA continuation should be based on individual evaluation of the benefit-risk ratio, tolerability, patient preference and cancer activity [Guidance]. For the treatment of VTE recurrence in cancer patients under anticoagulation, three options can be considered: (i) switch from VKA to LMWH when treated with VKA; (ii) increase in LMWH dose when treated with LMWH, and (iii) VCF insertion [Guidance]. For the prophylaxis of postoperative VTE in surgical cancer patients, use of LMWH o.d. or low dose of UFH t.i.d. is recommended; pharmacological prophylaxis should be started 12-2 h preoperatively and continued for at least 7-10 days; there are no data allowing conclusion that one type of LMWH is superior to another [1A]; there is no evidence to support fondaparinux as an alternative to LMWH [2C]; use of the highest prophylactic dose of LMWH is recommended [1A]; extended prophylaxis (4 weeks) after major laparotomy may be indicated in cancer patients with a high risk of VTE and low risk of bleeding [2B]; the use of LMWH for VTE prevention in cancer patients undergoing laparoscopic surgery may be recommended as for laparotomy [Guidance]; mechanical methods are not recommended as monotherapy except when pharmacological methods are contraindicated [2C]. For the prophylaxis of VTE in hospitalized medical patients with cancer and reduced mobility, we recommend prophylaxis with LMWH, UFH or fondaparinux [1B]; for children and adults with acute lymphocytic leukemia treated with l-asparaginase, depending on local policy and patient characteristics, prophylaxis may be considered in some patients [Guidance]; in patients receiving chemotherapy, prophylaxis is not recommended routinely [1B]; primary pharmacological prophylaxis of VTE may be indicated in patients with locally advanced or metastatic pancreatic [1B] or lung [2B] cancer treated with chemotherapy and having a low risk of bleeding; in patients treated with thalidomide or lenalidomide combined with steroids and/or chemotherapy, VTE prophylaxis is recommended; in this setting, VKA at low or therapeutic doses, LMWH at prophylactic doses and low-dose aspirin have shown similar effects; however, the efficacy of these regimens remains unclear [2C]. Special situations include brain tumors, severe renal failure (CrCl<30 mL min(-1) ), thrombocytopenia and pregnancy. Guidances are provided in these contexts.
  
  
  CONCLUSIONS
  Dissemination and implementation of good clinical practice for the management of VTE, the second cause of death in cancer patients, is a major public health priority.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Internal Medicine and Vascular Disease Unit, Saint-Louis Hospital, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Farge
authors.forename: P
authors.initials: P
authors.lastname: Debourdeau
authors.forename: M
authors.initials: M
authors.lastname: Beckers
authors.forename: C
authors.initials: C
authors.lastname: Baglin
authors.forename: R M
authors.initials: RM
authors.lastname: Bauersachs
authors.forename: B
authors.initials: B
authors.lastname: Brenner
authors.forename: D
authors.initials: D
authors.lastname: Brilhante
authors.forename: A
authors.initials: A
authors.lastname: Falanga
authors.forename: G T
authors.initials: GT
authors.lastname: Gerotzafias
authors.forename: N
authors.initials: N
authors.lastname: Haim
authors.forename: A K
authors.initials: AK
authors.lastname: Kakkar
authors.forename: A A
authors.initials: AA
authors.lastname: Khorana
authors.forename: R
authors.initials: R
authors.lastname: Lecumberri
authors.forename: M
authors.initials: M
authors.lastname: Mandala
authors.forename: M
authors.initials: M
authors.lastname: Marty
authors.forename: M
authors.initials: M
authors.lastname: Monreal
authors.forename: S A
authors.initials: SA
authors.lastname: Mousa
authors.forename: S
authors.initials: S
authors.lastname: Noble
authors.forename: I
authors.initials: I
authors.lastname: Pabinger
authors.forename: P
authors.initials: P
authors.lastname: Prandoni
authors.forename: M H
authors.initials: MH
authors.lastname: Prins
authors.forename: M H
authors.initials: MH
authors.lastname: Qari
authors.forename: M B
authors.initials: MB
authors.lastname: Streiff
authors.forename: K
authors.initials: K
authors.lastname: Syrigos
authors.forename: H
authors.initials: H
authors.lastname: Bounameaux
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D019985:Benchmarking; D032921:Consensus; D003299:Cooperative Behavior; D019317:Evidence-Based Medicine; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007391:International Cooperation; D009369:Neoplasms / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D018579:Patient Selection; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D015912:Thrombolytic Therapy; D013997:Time Factors; D016896:Treatment Outcome; D016306:Vena Cava Filters; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents; D005343:Fibrinolytic Agents