Anticoagulation in cancer patients – guidelines – pro

Pulmonary emboli is an indication for long term anticoagulation. Although generally oral warfarin is used, it is now recognized that it is not as effective in patients with thromboses secondary to cancer as are the low molecular weight heparins, such as Lovenox.

Low Molecular Weight Heparins are used for the prophylaxis or treatment of deep vein thrombosis. The decision to use LMWH instead of standard heparin or warfarin will depend upon the clinical scenario and individual patient factors such as risk of bleeding or availability of venous access.

Several studies have shown that patients with malignancy and thrombosis do not respond well to warfarin and many of them have recurrent DVT on warfarin. The National Comprehensive Cancer Network has issued its first guidelines for how to prevent deep vein thrombosis (DVT) in cancer patients and how to treat a DVT. The guidelines listed the following agents for anticoagulation:

Unfractionated heparin: 5,000 units subcutaneously three times a day.
Low molecular weight heparin, dosed according to standard operating procedures of individual institutions, with either dalteparin, enoxaparin or tinzaparin.
Pentasaccharide, fondaparinux, 2.5 mg subcutaneous daily.

The guidelines were revealed at the 11th annual conference of the NCCN — a consortium of 19 of the leading cancer centers in the country. They included recommendations for prophylaxis of venous thromboembolism in cases of patients with cancer or who are suspected of cancer. If they do not have contraindication for anticoagulation, then therapy was suggested with or without sequential compression devices. If there is a contraindication for anticoagulant therapy then use of compression devices, including graduated compression stocking, were considered.

For initial treatment of DVT or PE, either UFH or LMWH should be administered. For postoperative patients, an agent such as UFH, which has a short half life and is readily reversible, may be preferable. For more stable patients who are not at high risk for bleeding, LMWH is probably the treatment of choice.

Chronic VTE therapy with anticoagulants in cancer patients is a challenge. Many anticancer medications interact with oral anticoagulants (eg, warfarin), he added, and make it difficult to control the level of anticoagulation, particularly in cancer patients with more extensive disease. In a study of patients with and without cancer receiving oral anticoagulants, the VTE recurrence rate and risk of bleeding were substantially higher in patients with advanced cancer, particularly in the first 2 months of therapy. Recent results from the CLOT trial showed that the incidence of VTE recurrence was significantly lower in patients with advanced cancer receiving dalteparin (Fragmin) versus those receiving oral anticoagulation therapy over a 6-month period. The bottom line is that LMWH should be strongly considered in patients who have advanced metastatic cancer (Lee AY et al. N Engl J Med 2003;349:146–153).New guideline recommendations have been released for the use of anticoagulation in the prevention and treatment of venous thromboembolism (VTE) in patients with cancer. The guidelines, which were prepared by an international panel of researchers and are published in the October 29 Early Release Articles issue and were published in the December 1, 2007 issue of the Journal of Clinical Oncology.
The ASCO panel was a mix of world-famous experts in thrombosis and methodology, he added, and the resulting guidelines underwent extensive internal and external review by other leading experts before further review by the ASCO board of directors and their own reviewers.

Their guideline recommendations included the following:

Patients with cancer who are hospitalized should be considered candidates for VTE prophylaxis with anticoagulants in the absence of bleeding or other contraindications to anticoagulation.

Routine prophylaxis with an antithrombotic agent is not recommended for ambulatory patients during systemic chemotherapy, but patients receiving thalidomide or lenalidomide with chemotherapy or dexamethasone are at high risk for thrombosis and warrant prophylaxis.

All patients undergoing major surgical intervention for malignant disease should be considered for thromboprophylaxis.

Low molecular weight heparin (LMWH) represents the preferred agent for both the initial and continuing treatment of patients with cancer who have established VTE.

The impact of anticoagulants on survival of patients with cancer requires additional study and cannot be recommended at present.

Patients with cancer should be encouraged to participate in clinical trials designed to evaluate anticoagulant therapy as an adjunct to standard anticancer therapies.

INNOHEP is indicated for the treatment of acute symptomatic deep vein thrombosis with or without pulmonary embolism when administered in conjunction with warfarin sodium. The safety and effectiveness of INNOHEP were established in hospitalized patients. It is an FDA approved indication.

Lyman GH, Khorana AK, Falanga A, et al: American Society of Clinical Oncology guideline: Recommendations for
 venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 2007;25:

Agnes Y.Y. Lee Thrombosis in Cancer: An Update on Prevention, Treatment, and Survival Benefits of Anticoagulants
Highlights of the NCCN 11th Annual Conference: Clinical Practice Guidelines & Quality Cancer Care™, published as a supplement to The Oncology Report by Elsevier Oncology. © 2006 NCCN. ASH Education Book December 4, 2010 vol. 2010 no. 1 144-149

nccn, Anticoagulation 2012


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