Elevated Fibrin-Related Markers in Patients with Malignant Diseases Suspected of Having Thrombotic Disorders

Abstract

Background: Most patients with malignant diseases are frequently complicated with some type of thrombosis, such as disseminated intravascular coagulation (DIC) or deep vein thrombosis (DVT)/pulmonary embolism (PE). Objective: The cohort and retrospective study was designed to examine the frequency of thrombosis in patients with malignant diseases and to evaluate the efficacy of D-dimer and soluble fibrin (SF) for the diagnosis of thrombosis. Patients/Methods: The plasma concentrations of D-dimer and SF were measured in patients with malignant diseases suspected of having thrombosis. D-dimer and SF were measured using a latex aggregation assay. Results: Thrombosis was observed in 23.3% of the patients with malignant diseases. Disseminated intravascular coagulation was frequently observed in patients with hepatoma, and DVT/PE was frequently observed in patients with colon cancer, lung cancer, and uterine cancer. The plasma levels of D-dimer and SF were increased in malignant diseases, especially hepatoma. Plasma levels of D-dimer and SF were significantly higher in patients with thrombosis in comparison to patients without thrombosis. A receiver operating characteristic (ROC) analysis showed the D-dimer and SF levels to be useful in the diagnosis of thrombosis. Conclusion: Elevated D-dimer and SF levels might indicate a high risk of thrombosis in patients with malignant disease; however, these assays still need to be standardized.

Keywords

malignant disease DIC DVT D-dimer SF

References

Falanga A. The incidence and risk of venous thromboembolism associated with cancer and nonsurgical cancer treatment. Cancer Invest. 2009;27(1):105-115.

Varki A. Trousseau’s syndrome: multiple definitions and multiple mechanisms. Blood. 2007;110(6):1723-1729.

Bick RL Disseminated intravascular coagulation: a review of etiology, pathophysiology, diagnosis, and management: guidelines for care. Clin Appl Thromb Hemost. 2002;8(1):1-31.

Wada H. Disseminated intravascular coagulation. CCA. 2004;344(1-2):13-21.

De Cicco M. The prothrombotic state in cancer: pathogenic mechanisms. Crit Rev Oncol Hematol. 2004; 50(3):187-196.

Kwaan HC , Wang J. , Boggio LN Abnormalities in hemostasis in acute promyelocytic leukemia. Hematol Oncol. 2002;20(1):33-41.

Wada H. , Sase T. , Yamaguchi M. Hypercoagulant states in malignant lymphoma. Exp Oncol. 2005;27(3): 179-185.

Falanga A. , Barbui T. , Rickles FR Hypercoagulability and tissue factor gene upregulation in hematologic malignancies . Semin Thromb Hemost. 2008;34(2):204-210.

Landolfi R. , Di Gennaro L. , Falanga A. Thrombosis in myeloproliferative disorders; pathogenetic facts and speculation . Leukemia. 2008;22(11):2020-2028.

10.

Nalluri SR , Chu D. , Keresztes R. , Zhu X. , Wu S. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA. 2008;300(19):2277-2285.

11.

Akl EA , Terrenato I. , Barba M. , Sperati F. , Muti P. , Schünemann HJ Extended perioperative thromboprophylaxis in patients with cancer. A systematic review. Thromb Haemost. 2008;100(6):1176-1180.

12.

Linkins LA , Bates SM , Ginsberg JS , Kearon C. Use of different D-dimer levels to exclude venous thromboembolism depending on clinical pretest probability. J Thromb Haemost. 2004;2(8):1256-1260.

13.

Wada H. , Kobayashi T. , Abe Y. , et al. Elevated levels of soluble fibrin or D-dimer indicate high risk of thrombosis. J Thromb Haemost. 2006;4(6):1253-1258.

14.

Wada H. , Sakuragawa N. , Shiku H. Hemostatic molecular markers before onset of disseminated intravascular coagulation in leukemic patients. Semin Thromb Hemost. 1998;24(3):293-297.

15.

Wells PS , Anderson DR , Rodger M. , et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med. 2003;349(13):1227-1235.

16.

Houbouyan-Reveillard LL , Mihoubi A. , Houdijk WP , et al. Preliminary evaluation of two new rapid immunoturbidimetric D-dimer assays in patients with clinically suspected venous thromboembolism (VTE). Thromb Haemost. 2000;84(5):770-774.

17.

Righini M. , Le Gal G. , De Lucia S. , et al. Clinical usefulness of D-dimer testing in cancer patients with suspected pulmonary embolism. Thromb Haemost. 2006;95(4): 715-719.

18.

Carrier M. , Lee AY , Bates SM , Anderson DR , Wells PS Accuracy and usefulness of a clinical prediction rule and D-dimer testing in excluding deep vein thrombosis in cancer patients. Thromb Res. 2008;123(1):177-183.

19.

Taylor FB Jr , Toh CH , Hoots WK , Wada H. , Levi M. , and Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86(5):1327-1330.

20.

Matsuda M. , Terukina S. , Yamazumi K. , Maekawa H. , Soe G. A monoclonal antibody that recognizes the NH2-terminal conformation of fragment D. In: Henschen A , ed. Fibrinogen 4, Current Basic and Clinical Aspects, Matsuda, Iwanaga, Takada. 1990:43-48.

21.

Goldstein BJ , Mushlin AI Use of a single thyroxine test to evaluate ambulatory medical patients for suspected hypothyroidism. J Gen Intern Med. 1987;2(1):20-24.

22.

Kaido T. , Oe H. , Yoshikawa A. , Mori A. , Arii S. , Imamura M. Tissue factor is a useful prognostic factor of recurrence in hepatocellular carcinoma in 5-year survivors. Hepatogastroenterology. 2005;52(65): 1383-1387.

23.

Wada H. , Nagano T. , Tomeoku M. , et al. Coagulant and fibrinolytic activities in the leukemic cell lysates . Thromb Res. 1982;30(4):315-322.

24.

Wada H. , Kumeda Y. , Ogasawara Z. , et al. Plasminogen activators and their inhibitors in leukemic cell homogenates. Am J Hematol. 1993;42(2):166-170.

25.

Nomura H. , Wada H. , Mizuno T. , et al. Negative predictive value of D-dimer for diagnosis of venous thromboembolism. Int J Hematol. 2008;87(3):250-255.

26.

Ota S. , Wada H. , Nobori T. , et al. Diagnosis of deep vein thrombosis by plasma-soluble fibrin or D-dimer. Am J Hematol. 2005;79(4):274-280.

27.

Dempfle CE The use of soluble fibrin in evaluating the acute and chronic hypercoagulable state. Thromb Haemost. 1999;82(2):673-683.

28.

Minamikawa K. , Wada H. , Wakita Y. , et al. Increased activated protein C-protein C inhibitor complex levels in patients with pulmonary embolism. Thromb Haemost. 1994;71(2):192-194.

29.

Yamada N. , Wada H. , Nakase T. , et al. Hemostatic abnormalities in patients with pulmonary embolism compared with that in deep vein thrombosis. Blood Coagul Fibrinolysis . 1995;6(7):627-633.

30.

Wada H. , Mori Y. , Shimura M. , et al. Poor outcome in disseminated intravascular coagulation or thrombotic thrombocytopenic purpura patients with severe vascular endothelial cell injuries . Am J Hematol. 1998;58(3): 189-194.

31.

Wada H. , Mori Y. , Kaneko T. , et al. Elevated plasma levels of vascular endothelial cell markers in patients with hypercholesterolemia. Am J Hematol. 1993;44(2): 112-116.