How Best to Prevent VTE in Patients With Cancer

May 1, 2006

My patient has lung cancer with liver metastasis.

My patient has lung cancer with liver metastasis. Deep venous thrombophlebitis hasdeveloped, and his legs are chronically painful and swollen. A pulmonary embolismoccurred despite placement of a vena cava filter and warfarin therapy. The patientdoes not have accessible veins from which to draw blood to monitor his INR. Wouldan anticoagulant that did not require frequent venipuncture, such as low molecularweight heparin (LMWH), be effective in this setting? What are the options for longtermtreatment?
-MD

About 30% of patients who experience an episode of venous thromboembolism(VTE) (eg, deep vein thrombosis [DVT] or pulmonaryembolism) have a recurrence within the next 10 years.1 Althoughthe risk is highest within the first 3 to 6 months, VTE can recureven after 10 years.

Cancer and VTE recurrence. Independent predictors of VTE recurrenceinclude increasing age and body mass index, malignant neoplasm, and seriousneurologic disease with extremity paresis.1 Patients with cancer who receive cytotoxicor immunosuppressive therapyhave more than a 4-fold increased riskof VTE recurrence, while patients withcancer who do not receive chemotherapyhave a 2.2-fold increased risk.1

Inferior vena cava filters. Inferiorvena cava filters effectively preventpulmonary embolism in the shortterm, but they increase the long-termrisk of DVT.2,3 The development of pulmonaryembolism despite an inferiorvena cava filter suggests either malpositionof the filter or, more likely,thrombosis of the filter, with the embolismarising from a thrombus thatpropagates through the filter itself orthrough venous collaterals. Persistentbilateral leg swelling is further evidencethat points to obstruction of the inferior vena cava filter. Intensive effortsto reduce edema by leg elevation and the fitting of calf-high graduated compressionstockings that provide 30 to 40 mm Hg of pressure are thus warranted.

Warfarin therapy. Patients with cancer who have VTE and who are receivingoral anticoagulation therapy have a 3-fold increased risk of VTE recurrence-and a greater than 6-fold increased risk of major bleeding.4 Most recurrencestake place when the INR is subtherapeutic (eg, less than 2). Thus, the majority ofpatients with cancer who have VTE can be safely and effectively treated with standardoral anticoagulation therapy. Point-of-care devices for measurement of INRusually require only 15 µL of whole blood. You can easily collect this amount froma fingerstick, thus avoiding venipuncture.

VTE that is relatively resistant to oral vitamin K-inhibitor (warfarin) anticoagulationtherapy has been reported in patients with cancer-particularlythose in whom VTE is accompanied by disseminated intravascular coagulation(DIC).5-8 Thus, evaluation for DIC is important. Order such laboratorytests as prothrombin time, activated partial thromboplastin time, plateletcount, peripheral blood smear for microangiopathic hemolytic anemia, fibrino-gen, plasma fibrin-D-dimer, and soluble fibrin monomer complex levels, andcoagulation factor assays.

Low molecular weight heparin therapy. LMWH has several advantagesover warfarin.9 Unlike warfarin, LMWH dosages are based on body weight;thus, there is no need for laboratory monitoring or dose adjustment (Table).Also, the anticoagulant effect of LMWH is unaffected by either diet or concomitantuse of other drugs. Finally, both unfractionated heparin and LMWHare effective in patients with warfarin-resistant thrombosis.10,11

Two randomized studies-one that compared the long-term use ofLMWH with unfractionated heparin as therapy for VTE both in patients withcancer and in those without, and another that compared warfarin and LMWHfor the same use in a similar patient population-found no significant differencesin VTE recurrence or bleeding.12,13 However, the 2 studies were smalland included few cancer patients.

An international trial is under way to determine whether long-term LMWHtherapy is as effective and safe as oral anticoagulation in patients with cancer whohave VTE.14 Although firm recommendations must await the results of appropriatelydesigned trials, LMWH is a reasonable alternative to warfarin for patientssuch as this man.
-John A. Heit, MD
  Associate Professor of Medicine
  Mayo Medical School
  Rochester, Minn