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: