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. 1988 Dec;43(12):978–981. doi: 10.1136/thx.43.12.978

Abnormal haemostasis in small cell lung cancer.

R Milroy 1, J T Douglas 1, J Campbell 1, R Carter 1, G D Lowe 1, S W Banham 1
PMCID: PMC461606  PMID: 2467397

Abstract

Disorders of haemostasis and altered platelet activity have been documented in patients with malignant disease but their relation to response to treatment and prognosis are not known. Thrombin activity (fibrinopeptide A (FpA), plasmin mediated fibrinolysis (B beta 15-42) antigen), and platelet alpha granule release (beta thromboglobulin) were studied in 37 patients with small cell lung cancer to find out whether these indices show a relationship to chemoresponse. There was evidence of considerably increased thrombin activity, with a median fibrinopeptide A concentration of 13.2 (normal less than 4) pmol/ml, but only modestly increased fibrinolysis, with a median B beta 14-42 antigen concentration of 5.6 (normal less than 3) pmol/ml. Thus the ratio of fibrinopeptide A to B beta 15-42 concentration (FpA:B beta) was raised, with a median value of 2.2 (normal less than 1.33). In addition, 57% of patients had increased platelet alpha granule release, the median beta thromboglobulin concentration being 50 (normal less than 50) ng/ml. There was a significant association between increased thrombin generation and lack of response to chemotherapy. Furthermore, non-responders had higher FpA:B beta ratios. The same haemostatic markers were studied in nine patients who have been in complete remission for at least two years after chemotherapy for small cell lung cancer. There was a significant difference in thrombin activity and also in the ratio of thrombin activity to lysis between the pretreatment group and the group of two year survivors. Lack of response to chemotherapy appears to be related to increased thrombin activity. Such an association has not previously been reported in patients with malignant disease.

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Selected References

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  1. Al-Mondhiry H. Disseminated intravascular coagulation: experience in a major cancer center. Thromb Diath Haemorrh. 1975 Sep 30;34(1):181–193. [PubMed] [Google Scholar]
  2. Al-Mondhiry H., McGarvey V., Leitzel K. Interaction of human tumor cells with human platelets and the coagulation system. Thromb Haemost. 1983 Oct 31;50(3):726–730. [PubMed] [Google Scholar]
  3. Al-Mondhiry H. beta-Thromboglobulin and platelet-factor 4 in patients with cancer: correlation with the stage of disease and the effect of chemotherapy. Am J Hematol. 1983 Apr;14(2):105–111. doi: 10.1002/ajh.2830140202. [DOI] [PubMed] [Google Scholar]
  4. Brown J. M. A study of the mechanism by which anticoagulation with warfarin inhibits blood-borne metastases. Cancer Res. 1973 Jun;33(6):1217–1224. [PubMed] [Google Scholar]
  5. Brugarolas A., Elias E. G., Takita H., Mink I. B., Mittelman A., Ambrus J. L. Blood coagulation and fibrinolysis in patients with carcinoma of the lung. J Med. 1973;4(2):96–105. [PubMed] [Google Scholar]
  6. Donati M. B., Poggi A. Malignancy and haemostasis. Br J Haematol. 1980 Feb;44(2):173–182. doi: 10.1111/j.1365-2141.1980.tb01199.x. [DOI] [PubMed] [Google Scholar]
  7. Edlis H. E., Goudsmit A., Brindley C., Niemetz J. Trial of heparin and cyclophosphamide (NSC-26271) in the treatment of lung cancer. Cancer Treat Rep. 1976 May;60(5):575–578. [PubMed] [Google Scholar]
  8. Edwards R. L., Rickles F. R., Cronlund M. Abnormalities of blood coagulation in patients with cancer. Mononuclear cell tissue factor generation. J Lab Clin Med. 1981 Dec;98(6):917–928. [PubMed] [Google Scholar]
  9. Elias E. G., Shukla S. K., Mink I. B. Heparin and chemotherapy in the management of inoperable lung carcinoma. Cancer. 1975 Jul;36(1):129–136. doi: 10.1002/1097-0142(197507)36:1<129::aid-cncr2820360109>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  10. Farrell R. J., Duffy M. J., Moriarty M. J., Duffy G. J. Plasma concentrations of the platelet-specific beta-thromboglobulin in malignant disease. Br J Cancer. 1980 Jun;41(6):989–991. doi: 10.1038/bjc.1980.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gasic G. J., Gasic T. B., Galanti N., Johnson T., Murphy S. Platelet-tumor-cell interactions in mice. The role of platelets in the spread of malignant disease. Int J Cancer. 1973 May;11(3):704–718. doi: 10.1002/ijc.2910110322. [DOI] [PubMed] [Google Scholar]
  12. Gasic G. J., Gasic T. B., Murphy S. Anti-metastatic effect of aspirin. Lancet. 1972 Oct 28;2(7783):932–933. doi: 10.1016/s0140-6736(72)92581-0. [DOI] [PubMed] [Google Scholar]
  13. Gastpar H. Platelet-cancer cell interaction in metastasis formation: a possible therapeutic approcach to metastasis prophylaxis. J Med. 1977;8(2):103–114. [PubMed] [Google Scholar]
  14. Gralnick H. R., Abrell E. Studies of the procoagulant and fibrinolytic activity of promyelocytes in acute promyelocytic leukaemia. Br J Haematol. 1973 Jan;24(1):89–99. doi: 10.1111/j.1365-2141.1973.tb05730.x. [DOI] [PubMed] [Google Scholar]
  15. Gralnick H. R., Tan H. K. Acute promyelocytic leukemia: a model for understanding the role of the malignant cell in hemostasis. Hum Pathol. 1974 Nov;5(6):661–673. doi: 10.1016/s0046-8177(74)80037-7. [DOI] [PubMed] [Google Scholar]
  16. Jain R., Tabor D. C., Engle J. C. Plasma beta-thromboglobulin levels in lung cancer. South Med J. 1983 Nov;76(11):1380–1382. doi: 10.1097/00007611-198311000-00013. [DOI] [PubMed] [Google Scholar]
  17. Jamieson G. A., Bastida E., Ordinas A. Mechanisms of platelet aggregation by human tumor cell lines. Prog Clin Biol Res. 1982;89:405–413. [PubMed] [Google Scholar]
  18. Kudryk B., Robinson D., Netré C., Hessel B., Blombäck M., Blombäck B. Measurement in human blood of fibrinogen/fibrin fragments containing the B beta 15-42 sequence. Thromb Res. 1982 Feb 1;25(3):277–291. doi: 10.1016/0049-3848(82)90247-x. [DOI] [PubMed] [Google Scholar]
  19. Lyman G. H., Bettigole R. E., Robson E., Ambrus J. L., Urban H. Fibrinogen kinetics in patients with neoplastic disease. Cancer. 1978 Mar;41(3):1113–1122. doi: 10.1002/1097-0142(197803)41:3<1113::aid-cncr2820410346>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  20. Miller S. P., Sanchez-Avalos J., Stefanski T., Zuckerman L. Coagulation disorders in cancer. I. Clinical and laboratory studies. Cancer. 1967 Sep;20(9):1452–1465. doi: 10.1002/1097-0142(196709)20:9<1452::aid-cncr2820200912>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  21. Peuscher F. W., Cleton F. J., Armstrong L., Stoepman-van Dalen E. A., van Mourik J. A., van Aken W. G. Significance of plasma fibrinopeptide A (fpA) in patients with malignancy. J Lab Clin Med. 1980 Jul;96(1):5–14. [PubMed] [Google Scholar]
  22. Rickles F. R., Edwards R. L., Barb C., Cronlund M. Abnormalities of blood coagulation in patients with cancer. Fibrinopeptide A generation and tumor growth. Cancer. 1983 Jan 15;51(2):301–307. doi: 10.1002/1097-0142(19830115)51:2<301::aid-cncr2820510223>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  23. Rohwedder J. J., Sagastume E. Heparin and polychemotherapy for treatment of lung cancer. Cancer Treat Rep. 1977 Oct;61(7):1399–1401. [PubMed] [Google Scholar]
  24. Sack G. H., Jr, Levin J., Bell W. R. Trousseau's syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: clinical, pathophysiologic, and therapeutic features. Medicine (Baltimore) 1977 Jan;56(1):1–37. [PubMed] [Google Scholar]
  25. Stanford C. F. Anticoagulants in the treatment of small cell carcinoma of the bronchus. Thorax. 1979 Feb;34(1):113–116. doi: 10.1136/thx.34.1.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sun N. C., McAfee W. M., Hum G. J., Weiner J. M. Hemostatic abnormalities in malignancy, a prospective study of one hundred eight patients. Part I. Coagulation studies. Am J Clin Pathol. 1979 Jan;71(1):10–16. doi: 10.1093/ajcp/71.1.10. [DOI] [PubMed] [Google Scholar]
  27. Thornes R. D. Oral anticoagulant therapy of human cancer. J Med. 1974;5(1):83–91. [PubMed] [Google Scholar]
  28. Zacharski L. R., Henderson W. G., Rickles F. R., Forman W. B., Cornell C. J., Jr, Forcier R. J., Edwards R. L., Headley E., Kim S. H., O'Donnell J. F. Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate. Final report of VA Cooperative Study #75. Cancer. 1984 May 15;53(10):2046–2052. doi: 10.1002/1097-0142(19840515)53:10<2046::aid-cncr2820531007>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  29. Zacharski L. R., Henderson W. G., Rickles F. R., Forman W. B., Cornell C. J., Jr, Forcier R. J., Edwards R., Headley E., Kim S. H., O'Donnell J. R. Effect of warfarin on survival in small cell carcinoma of the lung. Veterans Administration Study No. 75. JAMA. 1981 Feb 27;245(8):831–835. [PubMed] [Google Scholar]
  30. Zacharski L. R., Henderson W. G., Rickles F. R., Forman W. B., Cornell C. J., Jr, Forcier R. J., Harrower H. W., Johnson R. O. Rationale and experimental design for the VA Cooperative Study of Anticoagulation (Warfarin) in the Treatment of Cancer. Cancer. 1979 Aug;44(2):732–741. doi: 10.1002/1097-0142(197908)44:2<732::aid-cncr2820440246>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]

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