Abstract
In order to predict a hypercoagulable state in patients with advanced breast cancer receiving medical treatment, the effects of Chemoendocrine therapy on the coagulation‐flbrinolytic systems were investigated prospectively. The patients were randomly divided into two groups. The ACT group had 38 patients, who received 20 mg/m2 adriamycin (ADM) i.v. on days 1 and 8, 100 mg cyclophosphamide (CPA) p.o. on days 1–14, and 20 mg tamoxifen (TAM) p.o. daily. The ACM group had 44 patients, who received 20 mg/m2 ADM i.v. on days 1 and 8, 100 mg CPA p.o. on days 1–14 and 1200 mg medroxyprogesterone acetate (MPA) p.o. daily. The treatment was repeated every 28 days until there was evidence of progressive disease or until the full ADM dose (550 mg/m2) had been given. The following 9 hematologic parameters were measured every 4 weeks: alpha 2‐plasmin inhibitor plasmin complex (PIC), anti‐thrombin‐III (AT‐III), D‐dimer (Dd), fibrinogen (Fg), plasminogen (Pg), protein C (PC), thrombin‐antithrombin‐III complex (TAT‐III), tissue plasminogen activator (t‐PA), and factor × (FX). Compared to the ACT group, patients in the ACM group showed significantly higher values of AT‐III and PC, which exceeded the normal ranges. The levels of Pg, t‐PA and FX were significantly higher in the ACM group than in the ACT group, but were still within the normal ranges. The levels of TAT‐III, Dd and PIC decreased in the ACT group and were unchanged in the ACM group after the start of treatment. Fg remained unchanged in both groups after the start of treatment. One patient in the ACM group had thrombophlebitis of the lower extremities with high levels of TAT‐III, Dd and PIC and a decrease of Fg, but her condition returned to normal after reduction of the MPA dose. Although these data are not directly indicative of a hypercoagulable state in patients receiving Chemoendocrine therapy, changes in AT‐III, TAT‐III, Dd and PIC should be monitored carefully when this type of treatment is given.
Keywords: Tamoxifen, Medroxyprogesterone acetate, Coagulation, Fibrinolysis, Breast cancer
Full Text
The Full Text of this article is available as a PDF (377.0 KB).
REFERENCES
- 1. ) Lipton , A. , Harvey , H. and Hamilton , R. W.Venous thrombosis as a side effect of tamoxifen treatment . Cancer Treat. Rep. , 68 , 887 – 889 ( 1984. ). [PubMed] [Google Scholar]
- 2. ) Hendrik , A , and Subramanian , V. P.Tamoxifen and thromboembolism . J. Am. Med. Assoc. , 243 , 514 – 515 ( 1980. ). [PubMed] [Google Scholar]
- 3. ) Yamamoto , H. , Noguchi , S. , Miyauchi , K. , Inaji , H. , Imaoka , S. , Koyama , H. and Iwanaga , T.Changes in hematologic parameters during treatment with medroxy‐progesterone acetate for breast cancer . Jpn. J. Cancer Res. , 82 , 420 – 425 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. ) Saphner , T. , Tormey , D. C. and Gray , R.Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer . J. Clin. Oncol. , 9 , 286 – 294 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Elms , M. J. , Bunce , I. H. , Bundensen , P. G. , Rylatt , D. B. , Webber , A. J. , Masci , P. P. and Whitaker , A. N.Measurement of crosslinked fibrin degradation products — an immunoassay using monoclonal antibodies . Thromb. Haemostasis , 50 , 591 – 594 ( 1983. ). [PubMed] [Google Scholar]
- 6. ) Shimamoto , M. , Yoshimura , T. , Kimura , N. , Kita , M. , Hoshino , N. , Motoi , S. , Suehisa , E. , Nishimura , K. , Hayashi , C. and Miyai , K.Protein C in human plasma determined by homogeneous enzyme immunoassay with use of a centrifugal analyzer . Clin. Chem. , 34 , 1834 – 1838 ( 1988. ). [PubMed] [Google Scholar]
- 7. ) Pelzer , H. , Schwarz , A. and Heimburger , N.Determination of human thrombin‐antithrombin complex in plasma with an enzyme‐linked immunosorbent assay . Thromb. Haemostasis , 59 , 101 – 106 ( 1988. ). [PubMed] [Google Scholar]
- 8. ) Bergsdorf , N. , Nilsson , T. and Wallen , P.An enzyme‐linked immunosorbent assay for determination of tissue plasminogen activator applied to patients with thromboembolic disease . Thromb. Haemostasis , 50 , 740 – 744 ( 1983. ). [PubMed] [Google Scholar]
- 9. ) Dati , F. , Barthels , M. , Conard , J. , Flueckiger , J. , Girolami , A. , Haenseler , E. , Huber , J. , Keller , F. , Kolde , H. J. , Mueller‐Berghaus , G. , Samama , M. and Thiel , W.Multicenter evaluation of a chromogenic substrate method for photometric determination of prothrombin time . Thromb, Haemostasis , 58 , 856 – 865 ( 1987. ). [PubMed] [Google Scholar]
- 10. ) Fukutomi , T. , Nanasawa , T. , Yamamoto , H. , Adachi , I. and Watanabe , T.The induction of a hypercoagulable state by medroxyprogesterone acetate in breast cancer patients . Jpn. J. Surg. , 20 , 665 – 670 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Scully , M. F. and Kakkar , V. V.Methods for semimicro or automated determination of thrombin, antithrombin, and heparin cofactor using the substrate, H‐D‐Phe‐Pip‐Arg‐p‐nitroanilide 2Hcl . Clin. Chim. Acta , 79 , 595 – 602 ( 1977. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Harpel , P. C.Alpha 2‐plasmin inhibitor and alpha 2‐macroglobulin‐plasmin complexes in plasma . J. Clin. Invest. , 68 , 46 – 55 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. ) Love , R. R. , Surawicz , T. S. and Williams , E. C.Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifen therapy . Arch. Intern. Med. , 152 , 317 – 320 ( 1992. ). [PubMed] [Google Scholar]
- 14. ) Bounameaux , H. , Cirafici , P. , De Moerloose , P. , Schneider , P. A. , Slosman , D. , Reber , G. and Unger , P. F.Measurement of D‐dimer in plasma as diagnostic aid in suspected pulmonary embolism . Lancet , 337 , 196 – 200 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Rosso , R. , Boccardo , F. , Canobbio , L. , Queirolo , M. A. , Zarcone , D. and Brema , F.Effects of high‐dose medroxyprogesterone acetate on blood‐clotting factors and platelet function . In “ Proceedings of the International Symposium on Medroxyprogesterone Acetate ,” ed. Cavalli F. , McGuire W. L. , Pannuti F. , Pellegrini A. and Robustelli Delia Cuna G. , pp. 151 – 157 ( 1982. ). Excerpta Medica; , Amsterdam‐Oxford‐Princeton . [Google Scholar]