Thromb Haemost 2002; 88(05): 745-749
DOI: 10.1055/s-0037-1613296
Review Article
Schattauer GmbH

Coagulation Markers Predict Survival in Cancer Patients

J. H. Beer
1   Department of Medicine, Kantonsspital Baden
,
A. Haeberli
2   Department of Medicine, Laboratory for Thrombosis Research, University Hospital of Bern
,
A. Vogt
2   Department of Medicine, Laboratory for Thrombosis Research, University Hospital of Bern
,
K. Woodtli
2   Department of Medicine, Laboratory for Thrombosis Research, University Hospital of Bern
,
E. Henkel
2   Department of Medicine, Laboratory for Thrombosis Research, University Hospital of Bern
,
Th. Furrer
3   Institute for Medical Oncology, University Hospital of Bern, Switzerland
,
M. F. Fey
3   Institute for Medical Oncology, University Hospital of Bern, Switzerland
› Author Affiliations
Supported by the Swiss National Science Foundation, Grant-No. 31-40’822.94 (to JHB) and the Swiss Cancer League (subsections Bern and Solothurn, to JHB)
Further Information

Publication History

Received 20 August 2001

Accepted after resubmission 01 August 2002

Publication Date:
08 December 2017 (online)

Summary

In order to prospectively evaluate the predictive value of coagulation markers such as the fibrin Ddimer for survival of cancer patients, we analyzed their role in a prospective study at a University Hospital Institute of Medical Oncology.

268 consecutive outpatients with cancer were included, 72 in remission and 196 with active disease. All cause mortality in relation to the marker levels was measured.

99/268 patients died during the observation period of 4484 patient months (mean: 17 months). Patients with active disease had a significant, 1.5-5-fold increased marker concentration compared to patients in remission. When analyzed in quartiles, the data showed a lower than predicted death rate in the first quartile and a significantly elevated mortality in the fourth marker quartile. The odds ratio for death predicted by the fibrin monomer (FM) in the fourth vs. the first quartile was 4.1 (95% C. I.: 1.7-9.7) and p = 0.005 for the multivariate analysis of the markers.

We conclude that a single determination of coagulation markers, particularly of TAT, FM, and Ddimer is sufficient to strongly predict survival in cancer patients over the following 1-3 years.

* Presented in part at the 29th annual Meeting of the Swiss Society of Internal Medicine, 2nd-5th April 1995 and published in abstract form in the Schweiz Med Wschr 1997; 127 (Suppl 88) and in Blood 1997; 90 (Suppl 104).


 
  • References

  • 1 De Moerloose P. D-dimer assays for the exclusion of venous thromboembolism which test for which diagnostic strategy. Thromb Haemost 2000; 83: 180-1.
  • 2 Genewein U, Haeberli A, Straub PW, Beer JH. Rebound after cessation of oral anticoagulant therapy: the biochemical evidence. British J of Haematology 1996; 92: 479-85.
  • 3 Mombelli G, Im VHof, Haeberli A, Straub PW. Effect of heparin on plasma fibrinopeptide A in patients with acute myocardial infarction. Circulation 1984; 69: 684-9.
  • 4 Trousseau A. Phlegmasia alba dolens. Clinique Médicale de l’Hôtel-Dieux de Paris. 3rd ed. J-B Ballière et fils: Paris; 1865: 654-712.
  • 5 Kempin SJ. Hemostatic defects in cancer patients. Cancer Investigation 1997; 15: 23-36.
  • 6 Edwards CN, Warren J, Armstrong L, Donnelly PK. D-dimer: a useful marker of disease stage in surgery for colorectal cancer. Brit J of Surgery 1993; 1404-5.
  • 7 Kakkar AK, Lemoine NR, Scully MF, Tebbutt S, Williamson RCN. Tissue factor expression correlates with histological grade in human pancreatic cancer. Brit J of Surgery 1995; 82: 1101-4.
  • 8 Kakkar AK, DeRuvo N, Chinswangwatanakul V, Tebbutt S, Williamson RCN. Extrinsic-pathway activation in cancer with high factor VIIa and tissue factor. Lancet 1995; 346: 1004-5.
  • 9 Shoji M, Hancock WW, Keisuke A, Micko C, Casper KA, Baine RM. et al. Activation of coagulation and angiogenesis in cancer (Immunohistochemical Localization in Situ of Clotting Proteins and Vascular Endothelial Growth Factor in Human Cancer). Am J Pathol 1998; 152: 399-411.
  • 10 Verheul HMW, Hoekman K, Lupu F, Broxterman HJ, van der Valk P, Kakkar AK. et al. Platelet and Coagulation Activation with Vascular Endothelial Growth Factor Generation in Soft Tissue Sarcomas. Clin Cancer Res 2000; 06: 166-71.
  • 11 Tripodi A, Cattaneo M, Molteni M, Cesana BM, Mannucci PM. Changes of prothrombin fragment 1+2 (F1+2) as a function of increasing intensity of oral anticoagulation. Thromb Haemost 1998; 79: 571-3.
  • 12 Bottasso B, Mari D, Coppola R, Santoro N, Vaglini M. Hypercoagulability and hyperfibrinolysis in patients with melanoma. Thromb Research 1996; 81: 345-52.
  • 13 Buccheri G, Ferrigno D, Ginardi C. Zuliani Haemostatic abnormalities in lung cancer: Prognostic implications. Eur J Cancer 1997; 33: 50-5.
  • 14 Geiser Th, Sturzenegger M, Genewein U, Haeberli A, Beer JH. Mechanisms of cerebrovascular events as assessed by procoagulant activity, cerebral microemboli, and platelet microparticles in patients with prosthetic heart valves. Stroke 1998; 29: 1770-7.
  • 15 Smorenburg SM, Hettiarachchi RJK, Vink R, Büller HR. The effects of unfractionated heparin on survival in patients with malignancy – a systematic review. Thromb Haemost 1999; 82: 1600-4.
  • 16 Green D, Hull RD, Brant R, Pineo GF. Lower mortality in cancer patients treated with low molecular heparins vs standard heparin. Lancet 1992; 339: 1476.
  • 17 Schulman S, Lindmarker P. Incidence of cancer after prophylaxis with warfarin against recurrent venous thromboembolism. N Engl J Med 2000; 342: 1953-8.
  • 18 Mannucci P. Markers of hypercoagulability in cancer patients. Haemostasis 1997; 27: 25-31.
  • 19 Den Ouden M, Ubachs JMH, Stoot JE, van Wersch JW. Thrombin-antithrombin III and D-dimer plasma levels in patients with benign or malignant ovarian tumours. Scand J Clin Lab Invest 1998; 58: 555-9.
  • 20 Humphries MJ, Olden K, Yamada KM. A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells. Science 1986; 233: 467-70.
  • 21 Tricerri A, Vangeli M, Errani AR, Guidi L, Canetta M. et al. Plasma thrombin-antithrombin complexes, latent coagulation disorders and metastatic spread in lung cancer: A longitudinal study. Oncology 1996; 53: 455-60.
  • 22 Edgington TS. Activation of the coagulation system in association with neoplasia. J Lab Clin Med 1980; 96: 1-4.
  • 23 Rickles FR, Edwards RL, Barb C, Cronlund M. Abnormalities of blood coagulation in patients with cancer Fibrinopeptide A generation and tumor growth. Cancer 1983; 51: 301-7.