[A case of bleeding tendency due to warfarin in a patient treated with chemotherapy by S-1].

Abstract A 82-year-old male patient had suffered from a cancer of the papilla of Vater. After the operation, he received 4 courses of gemcitabine(GEM)adjuvant chemotherapy and warfarin(WF)administration because of thrombosis in the left internal jugular vein. Since the tumors re-grew, GEM was discontinued, and chemotherapy including S-1 and GEM was examined. However, the chemotherapy could not be continued because of edema in both lower legs and tassel midway in the 2nd course. Because of a bleeding tendency(non-measurable INR(international normalized ratio of prothrombin time)), WF administration was discontinued on the 11th day after S-1/GEM combined therapy was suspended. On the following day, although the INR value recovered to 1.7, it gradually worsened and the symptoms of pulmonary embolism developed on the 13th day. Then, INR was controlled by continuous infusion of heparin. Since the INR level decreased after that, in addition to heparin, re-medication of WF was performed. We tried to analyze the genotype of a patient, who had a tendency to bleed by coadministration of WF with S-1, in terms of hepatic cytochrome P-450(CYP)2C9 and vitamin K epoxide reductase complex subunit 1(VKORC1). We also measured the plasma concentration of S-and R-WF by HPLC after obtaining informed consent from the patient. We found that he is homozygous for CYP2C9 1/1 and for A/A of VKORC1(-1639G>A). The obtained data did not show the abnormalities of blood coagulation. Because the genotype of a patient with a tendency to bleed was a major type in a Japanese population, fine monitoring of INR is required in order to prevent side effects of blood coagulation by S-1 and WF coadministration, regardless of patient genotypes.