Thromb Haemost 1993; 69(02): 112-114
DOI: 10.1055/s-0038-1651564
Original Article
Clinical Studies
Schattauer GmbH Stuttgart

Increased Plasma Thrombomodulin in Cancer Patients

Anne Karin Lindahl
The Haematological Research Laboratory, Åker Hospital, Oslo, Norway
,
Marie-Claire Boffa
1   The Unité 353 INSERM, Hôpital Saint-Louis, Paris, France
,
Ulrich Abildgaard
The Haematological Research Laboratory, Åker Hospital, Oslo, Norway
› Author Affiliations
Further Information

Publication History

Received 03 July 1992

Accepted after revision 13 October 1992

Publication Date:
03 July 2018 (online)

Summary

Plasma samples from 35 patients with colorectal cancer, 16 patients with pancreatic cancer and 46 patients with various cancers in the terminal stage were analysed for soluble plasma thrombomodulin with an ELISA method. At time of diagnosis and before primary treatment, the patients with colorectal cancer had normal plasma TM levels. In the patients who developed disseminated disease, the mean plasma TM level increased significantly. In the patients with pancreatic cancer, the mean plasma TM level was increased already at time of primary treatment. The TM level increased further with progress of the pancreatic cancer. In the patients with various cancer types in the terminal stage, the mean TM was also significantly increased compared to healthy controls. Great individual variation in the plasma TM level was observed, as well as great variation of mean TM level between the various cancer types. There was no significant correlation between the TM levels and the levels of tissue factor pathway inhibitor, another endothelial coagulation inhibitor, which increased with progress of malignant disease. This may indicate different underlying mechanisms for the increased plasma levels.

 
  • References

  • 1 Esmon CT, Owen WG. Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. Proc Natl Acad Sci USA 1981; 78: 2249-2252
  • 2 Esmon CT. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 1989; 264: 4743-4746
  • 3 Dittman WA, Majerus PW. Structure and function of thrombomodulin: A natural anticoagulant. Blood 1990; 75: 329-336
  • 4 Ishii H, Majerus PW. Thrombomodulin is present in human plasma and urine. J Clin Invest 1985; 76: 2178-2181
  • 5 Ishii H, Uchiyama H, Kazama M. Soluble thrombomodulin antigen in conditioned medium is increased by damage of endothelial cells. Thromb Haemostas 1991; 65: 618-623
  • 6 Boffa MC, Karmochkine M, Berard M. Plasma thrombomodulin as a marker for endothelium damage. Nouv Rev Fr Hematol 1991; 33: 529-530
  • 7 Karmochkine M, Boffa MC, Piette JC, Cacoub P, Wechsler B, Godeau P, Juhan I, Weiller PJ. Increase in plasma thrombomodulin in lupus erythematosus with antiphospholipid antibodies. Blood 1992; 837-838 (Letter)
  • 8 Takano S, Kimura S, Ohdama S, Aoki N. Plasma thrombomodulin in health and disease. Blood 1990; 76: 2024-2029
  • 9 Iwashima Y, Sato T, Watanabe K, Osohima E, Hiraishi S, Ishii H, Kazama M, Makino I. Elevation of plasma thrombomodulin level in diabetic patients with early diabetic nephropathy. Diabetes 1990; 39: 983-988
  • 10 Takahashi H, Hanano M, Wada K, Tatewaki W, Niwano H, Tsubouchi J, Nakano M, Nakamura T, Shibata A. Circulation thrombomodulin in thrombotic thrombocytopenic purpura. Am J Hematol 1991; 38: 174-177
  • 11 Sandset PM, Abildgaard U, Pettersen M. A sensitive assay of extrinsic coagulation pathway inhibitor (EPI) in plasma and plasma fractions. Thromb Res 1987; 47: 389-400
  • 12 Bajaj MS, Kuppuswamy MN, Saito H, Spitzer SG, Bajaj SP. Cultured normal hepatocytes do not synthesize lipoprotein-associated coagulation inhibitor: evidence that endothelium is the principal site of its synthesis. Proc Natl Acad Sci 1990; 87: 8869-8873
  • 13 Lindahl AK, Sandset PM, Abildgaard U, Andersson TR, Harbitz TB. Increased levels of extrinsic pathway inhibitor and decreased levels of other coagulation inhibitors in advanced cancer. Acta Chir Scand 1989; 155: 389-393
  • 14 Lindahl AK, Ødegaard OR, Sandset PM, Harbitz TB. Plasma coagulation and inhibition in pancreatic cancer: changes during progress of disease. Cancer 1992; 70: 2067-2072
  • 15 Handeland G, Abildgaard U, Aasen AO. Simplified assay for antithrombin III activity using chromogenic peptide substrates. Scand J Haematol 1983; 35: 627-636
  • 16 Ödegaard OR, Try K, Andersson TR. Protein C: an automated activity assay. Haemostasis 1988; 18: 55-56
  • 17 Lindahl AK, Abildgaard U, Stokke G. Release of extrinsic pathway inhibitor after heparin injection: increased response in cancer patients. Thromb Res 1990; 59: 651-656
  • 18 Silverberg JM, Gordon S, Zucker S. Identification of tissue factor in two pancreatic cancer cell lines. Cancer Res 1989; 49: 5443-5447
  • 19 McKay DG, Mansell H, Hertig AR. Carcinoma of the body and the tail of the pancreas with fibrin thrombosis and fibrinogenopenia. Cancer 1953; 6: 862-869
  • 20 Nawa K, Itani T, Ono M, Sakano K, Marumoto Y, Iwamoto M. The glycosaminoglycan of recombinant human soluble thrombomodulin affects antithrombotic activity in a rat model of tissue-factor induced disseminated intravascular coagulation. Thromb Haemostas 1992; 67: 366-370
  • 21 Gomi K, Zushi M, Honda G, Kawahara S, Matsuzaki O, Kanabayashi T, Yammamoto S, Maruyama I, Suzuki K. Antithrombotic effect of recombinant human thrombomodulin on thrombin-induced thromboembolism in mice. Blood 1990; 75: 1396-1399
  • 22 Lindahl AK, Sandset PM, Abildgaard U. Indices of hypercoagulation in malignancy, as compared to in acute inflammation and acute infarction. Haemostasis 1990; 20: 253-262