Table 8 Summary of available international guidelines concerning the treatment of established VTE

NCCN (2014) [9]

LMWH is recommended for the initial treatment of established VTE in cancer patients. (Category 1)

1. LMWH (category 1) is preferred for the first 6 months as monotherapy without warfarin in patients with proximal DVT or PE and prevention of recurrent VTE in patients with advanced or metastatic cancer.

2. If warfarin is selected for chronic anticoagulation (category 2b), initiate warfarin concurrently with the parenteral agent used for acute therapy and continue both therapies for at least 5 days and until the INR 2 for 24 h.

During the transition to warfarin monotherapy, the INR should be measured at least twice weekly. Once the patient is on warfarin alone, the INR should be measured initially at least once weekly. Once the patient is on a stable dose of warfarin with an INR between 2 and 3, INR testing can be gradually decreased to a frequency no less than once monthly.

ESMO (2011) [10]

LMWH is recommended for the initial treatment of established VTE in cancer patients.

Long-term treatment for 6 months with 75% to

80% (that is, 150 U/kg once daily) of the initial dose of LMWH is safe and more effective than treatment with a VKA. This schedule is recommended for Long term anticoagulant therapy in cancer patients [I, A].

ISTH (2013) [12]

1. LMWH is recommended for the initial treatment of established VTE in cancer patients [grade 1B].

1. LMWHs are preferred over VKA for the early maintenance treatment (10 days to 3 months) and long-term treatment (beyond 3 months) of VTE in cancer patients [grade 1A].

Values and preferences: LMWHs are easier to use than UFH.

2. Fondaparinux and UFH can be also used for the initial treatment of established VTE in cancer patients [grade 2D].

Values and preferences: daily subcutaneous injection may represent a burden for patients.

2. Idraparinux is not recommended for the early maintenance treatment (10 days to 3 months) and the long-term treatment (beyond 3 months) of VTE in cancer patients; idraparinux is currently not available on the market [grade 2C]. Values and preferences: idraparinux once weekly is easier to use than UFH or LMWH.

Values and preferences: fondaparinux is easier to use than UFH.

3. LMWH should be used for a minimum of 3 months to treat established VTE in cancer patients; however, patients were treated for 6 months in the largest study in this setting [grade 1A].

Values and preferences: daily subcutaneous injection may represent a burden for patients.

4. After 3 to 6 months, termination or continuation of anticoagulation (LMWH or VKA) should be based on individual evaluation of the benefit-risk ratio, tolerability, patients’ preference, and cancer activity [best clinical practice, in the absence of data].

European society of cardiology (ESC) [14]

LMWH should be administered in the acute phase

1. LMWH administered in the acute phase Should be continued over the first 3 to 6 months and is considered as first-line therapy.

2. Chronic anticoagulation (beyond 3 months) may consist of continuation of LMWH, transition to VKA, or discontinuation of anticoagulation. The decisions should be made on a case-by-case basis.

3. Treatment of cancer-related VTE with fondaparinux and the new oral anticoagulants is limited.

American College of Chest Physician (ACCP) [13]

1. In patients with DVT of the leg and cancer, LMWH is suggested over VKA therapy (grade 2B).

2. In patients with DVT and cancer who are not treated with LMWH, VKA is suggested over dabigatran or rivaroxaban for long-term therapy (grade 2B).

3. In patients with DVT of the leg and active cancer, if the risk of bleeding is not high, extended anticoagulant therapy over 3 months of therapy is recommended (grade 1B), and if there is a high bleeding risk, extended anticoagulant therapy is suggested (grade 2B).

4. In patients with PE and cancer, the treatment is as suggested in patient with DVT.