**9. Treatment of VTE**

### **Several studies have addressed treatment of VTE in patients with cancer:**


Compared with warfarin, LMWHs generally reduce the overall risk of recurrent VTE when used for the extended treatment of VTE, a finding confirmed by a recently published Cochrane systematic review (221). Furthermore, LMWHs do not increase major bleeding

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rates and appear to be as safe as VKAs. These findings, like those seen in the prevention trials, appear to be related to the dose and the duration of therapy.

The standard treatment for acute VTE is anticoagulant therapy. For initial therapy, subcutaneous (SC) LMWH is as effective and safe as intravenous UFH (28, 29). LMWHs are administered once or twice daily by SC injection, have weight-adjusted dosing and do not usually require laboratory monitoring. These advantages over UFH allow LMWHs to be given on an outpatient basis and reduce the need for hospitalization.

Duration of therapy: Duration of anticoagulant therapy has not been addressed in cancer patients. Based on the accepted concept that the risk of recurrent thrombosis is increased in the presence of any ongoing risk factor, it is generally recommended that patients with metastases continue with ''indefinite'' therapy because metastatic malignancy is a persistent risk factor. In those without metastases, anticoagulant treatment is recommended for as long as the cancer is ''active'' and while the patient is receiving antitumor therapy.

Secondary prophylaxis: Oral anticoagulant therapy with a vitamin K antagonist can be started on the same day as heparin therapy to begin secondary prophylaxis. To effectively reduce recurrent VTE without excessive bleeding, the dose of oral anticoagulants must be adjusted to maintain the INR within a therapeutic range of 2.0 to 3.0. This usually requires twice weekly blood work for the first 1 to 2 weeks until a stable dose is identified. Using this regimen, the annual incidence of recurrent VTE in patients without cancer is approximately 8%, whereas the risk of recurrence is two- to threefold higher in patients with cancer.

The higher failure rate in cancer patients may reflect the greater difficulty in maintaining therapeutic INR levels because of multiple drug interactions, gastrointestinal upset, vitamin K deficiency, liver dysfunction and poor venous access. Also, temporary discontinuation of anticoagulant therapy is often necessary during periods of thrombocytopenia and to accommodate invasive procedures. Such interruptions can cause lengthy periods of inadequate anticoagulation because vitamin K antagonists have a delayed onset of action and a prolonged period of clearance. Furthermore, warfarin failure, i.e. recurrent VTE despite maintaining therapeutic INR levels, is not uncommonly reported in cancer patients on oral anticoagulant therapy.
