Tamoxifen-associated venous thrombosis and activated protein C resistance due to factor V Leiden.
BACKGROUND
Thromboembolic events are well recognized complications of cancers and their treatment. Tamoxifen, an antiestrogen used in the treatment of breast carcinoma and other malignancies, has been associated with thrombotic events. Activated protein C resistance due to Factor V Leiden is the most prevalent inherited prothrombotic defect in populations of European descent and has been reported as a major cofactor in the development of thrombosis in women receiving estrogens.


METHODS
The authors report three patients who developed thromboembolic complications while receiving tamoxifen. These patients were studied for the presence of activated protein C resistance by coagulation assay and the presence of Factor V Leiden by molecular analysis.


RESULTS
All three patients had resistance to activated protein C by coagulation assay and were determined to be heterozygous for Factor V Leiden by molecular analysis.


CONCLUSIONS
The authors propose that inheritance of Factor V Leiden significantly increases the risk of thrombosis in patients who receive tamoxifen therapy. All patients prescribed tamoxifen should be carefully questioned regarding personal and family histories of thrombosis and, when indicated, screened for Factor V Leiden.
Weitz
I C
IC
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033, USA.
Israel
V K
VK
Liebman
H A
HA
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy; D004965:Estrogen Antagonists / Q000009:adverse effects*; D005165:Factor V / Q000235:genetics*; D005260:Female; D005268:Femoral Vein; D006579:Heterozygote; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011486:Protein C / Q000502:physiology*; D011655:Pulmonary Embolism / Q000139:chemically induced; D012878:Skin Neoplasms / Q000188:drug therapy; D013629:Tamoxifen / Q000009:adverse effects*; D013924:Thrombophlebitis / Q000139:chemically induced*; D013927:Thrombosis / Q000139:chemically induced
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D011486:Protein C; C095381:factor V Leiden; D013629:Tamoxifen; D005165:Factor V