CLINICAL-SIGNIFICANCE OF THE FV-Q(506) MUTATION IN UNSELECTED ONCOLOGY PATIENTS

PURPOSE: A common germline mutation in the factor V gene (FV:Q(506)) h as been associated with hypercoagulability in families with heritable predisposition to thrombosis. We examined the prevalence and clinical significance of the FV:Q(506) mutation in cancer patients. PATIENTS AN D METHODS: We performed a retrospective cohort study by examining 353 consecutive, unselected patients in a general hematology/oncology clin ic. We ascertained risk factors, obtained the clinical clotting histor y, and determined the heterozygous or homozygous presence of the FV:Q( 506) allele for each patient. RESULTS: We detected a germline mutation in 5.4% (19 of 353) of patients, of whom 18 were heterozygous and 1 w as homozygous for the FV:Q(506) mutant allele. In 17 of 18 heterozygou s patients, there was no history of venous thrombosis or catheter-asso ciated thrombosis. These asymptomatic patients included 13 patients wh o had been diagnosed with cancer or leukemia for a mean of 66.2 months (median 69) and had received a variety of local and systemic treatmen ts. In contrast, 1 of 18 heterozygous and 1 of 1 homozygous patients h ad developed deep vein thrombosis that was associated, respectively, w ith either recurrent thrombotic events or a strong family history for pulmonary embolus. CONCLUSIONS: Routine screening for the FV:Q(506) mu tation in cancer patients without a personal or family history for ven ous thrombosis is not helpful in guiding management. In contrast, an e pisode of venous thrombosis in a patient with a mutant germline FV:Q(5 06) allele was associated with recurrent thrombotic events. These find ings suggest that patients heterozygous for the FV:Q(506) allele may r equire an independent ''susceptibility'' element to manifest a venous hypercoagulable state. In addition, only 2 of 25 clinic patients with a venous clot carried the FV:Q(506) allele suggesting this genetic def ect plays a minor role in the hypercoagulable state of cancer.