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To the Editor: Two patients with advanced breast cancer who were receiving long-term and stable anticoagulation therapy with warfarin developed extreme hypoprothrombinemia when treated with trastuzumab (Herceptin).

Report of Cases

A 75-year-old woman with locally advanced breast cancer diagnosed in 1989 was treated with chemotherapy, mastectomy, radiation therapy, and long-term hormonal suppression. The patient developed deep venous thrombosis and pulmonary embolism in 1990, and was treated with heparin and subsequently with warfarin. International normalized ratios (INRs) ranged from 2.1 to 2.8 while taking warfarin sodium 5 mg and 7.5 mg on alternate days. In 1995, receptor-positive progressive cancer was treated sequentially with medroxyprogesterone acetate, anastrozole, paclitaxel, and doxorubicin.

In December 1998, when an enlarging axillary soft tissue mass was found to overexpress HER2/neu, trastuzumab therapy was initiated with a standard loading dose of 4 mg/kg and then weekly dosages of 2 mg/kg intravenously. After 10 doses of trastuzumab, the patient experienced severe epistaxis. . . . [Full Text of this Article]

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