Barriers to the long-term use of low-molecular weight heparins for treatment of cancer-associated thrombosis

Authors

  • A. K. WITTKOWSKY

    1. School of Pharmacy and Anticoagulation Services, University of Washington Medical Center, University of Washington, Seattle, WA, USA
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Ann K. Wittkowsky, University of Washington Medical Center, 1959 NE Pacific St, Box 356015, Seattle WA 98195, USA.
Tel.: +1 206 598 5626; fax: +1 206 598 6217; e-mail: akwitt@u.washington.edu

Several clinical trials have confirmed that the use of low-molecular weight heparins (LMWH) for the first 3–6 months of treatment for cancer-associated thrombosis is associated with reduced rates of thromboembolic recurrence and hemorrhagic complications compared to warfarin [1–3]. In addition, LMWH may result in lower mortality in patients with non-metastatic disease [4]. Current guidelines from the American College of Chest Physicians and the National Comprehensive Cancer Network recommend LMWH for the first 3–6 months of treatment for cancer-associated thrombosis [5,6]. LMHWs also offer simplified dosing and freedom from routine coagulation monitoring that may improve patient acceptance compared to warfarin therapy [7].

In an effort to the determine the rate of use of LMWH for the first 3–6 months of treatment for cancer-associated thrombosis, the medical records of 100 consecutive patients with acute cancer-associated thrombosis were reviewed. All patients were referred to a pharmacist-managed Anticoagulation Clinic between January 2005 and May 2006 for management of anticoagulant therapy. This clinic manages both warfarin and LMWH therapy, and clinic policies stipulate that LMWH be offered as the first-line treatment for cancer-associated thrombosis.

Demographic characteristics of the patients are described in Table 1. They were equally distributed with regard to sex, with a mean age of 57 years (range 26–87 years), and their underlying malignancies represented a wide range of solid tumors and hematologic malignancies. All patients had venous thromboembolism, either lower extremity deep vein thrombosis (DVT) (n = 44), pulmonary embolism (n = 38), both (n = 7), upper extremity DVT (n = 5); or thrombosis of other veins (n = 6).

Table 1.   Patient characteristics and treatment selection (n = 100)
  1. DVT, deep vein thrombosis; PE, pulmonary embolism; LMWH, low-molecular weight heparin; UFH, unfractionated heparin.

Female50
Mean age (range)57 years (range 26–87)
Cancer-associated thrombosis
 DVT44
 PE38
 DVT and PE 7
 Upper extremity DVT 5
 Miscellaneous venous thrombosis 6
Initial treatment of cancer-associated thrombosis
 LMWH for 3–6 months19
 LMWH/UFH for 5–7 days following warfarin for 3–6 months81
Reasons that LMWH was not used long term (n = 81)
 Not covered by medical insurance40 (49.4%)
 Physician preference26 (32.0%)
 Patient refused long-term injections11 (13.6%)
 Heparin-induced thrombocytopenia 2 (2.5%)
 Severe renal insufficiency 2 (2.5%)

During the first 3–6 months of anticoagulation, only 19 patients received LMWH for treatment of cancer-associated thrombosis. The remaining 81 patients received LMWH or unfractionated heparin for 5–7 days followed by oral anticoagulation with warfarin. As it was the policy of the Anticoagulation Clinic to recommend LMWH as first-line therapy in these patients, reasons for use of long-term warfarin instead of LMWH were recorded in the Anticoagulation Clinic records. The most common reason was that the patient's medical insurance did not cover the cost of LMWH and the patient could not afford the out-of-pocket cost (49.4%). For an additional 32% of patients, the referring physician preferred that the patient receive warfarin instead of LMWH. Eleven patients (13.5%) refused long-term injections despite being counselled about the benefits and advantages of LMWH over warfarin. Warfarin was appropriately selected instead of LMWH for two patients with a history of heparin-induced thrombocytopenia and two patients with several renal impairment (creatinine clearance < 30 mL min−1).

These data highlight significant barriers to the use of LMWHs for the treatment of cancer-associated thrombosis, and emphasize explicit opportunities to improve access to appropriate therapy. Educational efforts directed toward health insurance providers are necessary to increase coverage of these agents. In addition, greater exposure to current evidence-based guidelines may improve the extent to which referring oncologists prescribe and accept long-term LMWH for the treatment of cancer-associated thrombosis.

Acknowledgements

The assistance of Kelly Ng, Pharm.D., is gratefully acknowledged.

Disclosure of Conflict of Interest

The authors state that they have no conflict of interest.

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