View More View Less
  • 1 Municipal Hospital of Bács-Kiskun County Department of Pulmonology Pf. 149 H-6000 Kecskemét Hungary
Restricted access

Introduction: An increased disposition to thrombosis demonstrated by laboratory methods in patients with solid malignancies develops due to the activating effect of tumour cells on the haemostatic system. The development of this activating effect results from interactions between tumour cells and various components of the coagulation system (coagulation factors, platelets, endothelial cells, and fibrinolytic system) which leads from a prothrombotic state to the clinically overt disorders of the haemostatic system. Objectives: In a retrospective analysis, the authors sought for an answer to the following question: What is the type and frequency of haemostatic disorders that occurred in a large population of patients with solid malignancies? Methods: Between 1996 and 2004, solid malignancies have been diagnosed in 1381 patients by histological and/or cytological examinations. Most of the patients had primary bronchopulmonary carcinoma ( n = 1140). In the other patients the malignancies were of mammary, colorectal, renal, vesical, thyroidal, and pancreatic localisation; mesothelioma was diagnosed in six patients. Based on the staging examinations, the majority of patients were in an advanced clinical stage. Type and frequency of haemostatic disorders occurring in patients with solid malignancies were studied, with special regard to the occurrence of venous thromboembolism. Particular attention was given to the role of non-malignant co-morbidity in the development of haemostatic disorders. Results: Clinically overt haemostatic disorders were observed in 397 (28.7%) of the 1381 patients with malignancies. Deep vein thrombosis and acute pulmonary embolism were the most frequent ones ( n = 305; 22%). Migrating superficial thrombophlebitis, septic thrombosis, acute diffuse intravascular coagulation, and microangiopathic haemolytic anaemia occurred in 71 patients (6.7%). In 40% of patients with malignant diseases and associated haemostatic disorders, non-malignant co-morbidity has been observed with the dominance of various cardiac diseases as well as chronic obstructive pulmonary disease. In addition to the systemic causes leading to an increased disposition to thrombosis, the significantly increased local-regional tumour mass also contributed to the development of venous circulation disorder. Conclusions: Active cancer is often associated with a hypercoagulable state, which perturbs the haemostatic balance between anticoagulant and procoagulant forces, creating a prothrombotic state. The interaction between tumour cells and host cells involves a direct cell-to-cell interaction or an indirect mechanism by cytokine release. The hypercoagulable state in patients with a malignant disease may result in the occurrence of various clinically identifiable haemostatic system disorders: the most frequent one is venous thromboembolism (so-called secondary thrombosis). In cases of idiopathic venous thromboembolism, targeted examinations are warranted in order to prove or to preclude asymptomatic malignant diseases.

  • Trousseau, A.: Phlegmasia alba dolens. In Trousseau A. (ed.): Clinique medicale de I’Hotel-Dieu de Paris. Bailliere, Paris, 1865, 654–712.

    Trousseau A. , '', in Clinique medicale de I’Hotel-Dieu de Paris , (1865 ) -.

  • Giffin, M. R., Stanson, A. W., Brown, M. L. et al.: Deep venous thrombosis and pulmonary embolism. Risk of subsequent malignant neoplasm. Arch. Intern. Med., 1987, 147 , 1907–1911.

    Brown M. L. , 'Deep venous thrombosis and pulmonary embolism. Risk of subsequent malignant neoplasm ' (1987 ) 147 Arch. Intern. Med. : 1907 -1911.

    • Search Google Scholar
  • Blann, A. D., Lip, G. Y. H.: Virchow’s triad revisited: the importance of soluble coagulation factors, the endothelium, and platelets. Thromb. Res., 2001, 101 , 321–327.

    Lip G. Y. H. , 'Virchow’s triad revisited: the importance of soluble coagulation factors, the endothelium, and platelets ' (2001 ) 101 Thromb. Res. : 321 -327.

    • Search Google Scholar
  • Falanga, A., Marchetti, M., Vignoli, A.: Pathogenesis of thrombosis in cancer. In Lugassy, G., Falanga, A., Kakkar, A. K., Rickles, F. (eds): Thrombosis and Cancer. R. Taylor and Francis Group, London, 2004, 11–29.

    Vignoli A. , '', in Thrombosis and Cancer , (2004 ) -.

  • Nand, S., Fisher, S. G., Salgia, R., Fisher, R. I.: Hemostatic abnormalities in untreated cancer: incidence and correlation with thrombotic and hemorrhagic complications. J. Clin. Oncol., 1987, 5 , 1998–2003.

    Fisher R. I. , 'Hemostatic abnormalities in untreated cancer: incidence and correlation with thrombotic and hemorrhagic complications ' (1987 ) 5 J. Clin. Oncol. : 1998 -2003.

    • Search Google Scholar
  • Ruiz, M. A., Marugan, I., Estelles, A. et al.: The influence of chemotherapy on plasma coagulation and fibrinolytic systems in lung cancer patients. Cancer, 1989, 63 , 643–648.

    Estelles A. , 'The influence of chemotherapy on plasma coagulation and fibrinolytic systems in lung cancer patients ' (1989 ) 63 Cancer : 643 -648.

    • Search Google Scholar
  • Falanga, A.: Mechanism of hypercoagulation in malignancy and during chemotherapy. Haemostasis, 1998, 28 (Suppl. 3) , 50–60.

    Falanga A. , 'Mechanism of hypercoagulation in malignancy and during chemotherapy ' (1998 ) 28 Haemostasis : 50 -60.

    • Search Google Scholar
  • Falanga, A., Rickels, F. R.: Pathophysiology of the thrombophilic state in the cancer patients. Semin. Thromb. Hemost., 1999, 25 , 173–182.

    Rickels F. R. , 'Pathophysiology of the thrombophilic state in the cancer patients ' (1999 ) 25 Semin. Thromb. Hemost. : 173 -182.

    • Search Google Scholar
  • Rickles, F. R., Levine, M. N.: Venous thromboembolism in malignancy and malignancy in venous thromboembolism. Haemostasis, 1998, 28 (Suppl. 3) , 43–49.

    Levine M. N. , 'Venous thromboembolism in malignancy and malignancy in venous thromboembolism ' (1998 ) 28 Haemostasis : 43 -49.

    • Search Google Scholar
  • Baron, I. A., Gridley, G., Weiderpass, M. et al.: Venous thromboembolism and cancer. Lancet, 1998, 351 , 1077–1080.

    Weiderpass M. , 'Venous thromboembolism and cancer ' (1998 ) 351 Lancet : 1077 -1080.

  • Prandoni, P., Lensing, A. W. A., Buller, H. R. et al.: Deep-vein thrombosis and the incidence of subsequent symptomatic cancer. N. Eng. J. Med., 1992, 327 , 1128–1133.

    Buller H. R. , 'Deep-vein thrombosis and the incidence of subsequent symptomatic cancer ' (1992 ) 327 N. Eng. J. Med. : 1128 -1133.

    • Search Google Scholar
  • Ackerman, R. F., Estes, I. E.: Prognosis in idiopathic thrombophlebitis. Ann. Intern. Med., 1951, 34 , 902–910.

    Estes I. E. , 'Prognosis in idiopathic thrombophlebitis ' (1951 ) 34 Ann. Intern. Med. : 902 -910.

    • Search Google Scholar
  • Aderka, D., Brown, A., Zelicovski, A.: Idiopathic deep vein thrombosis in an apparently healthy patient as a premonitory sign of occult cancer. Cancer, 1986, 57 , 1846–1849.

    Zelicovski A. , 'Idiopathic deep vein thrombosis in an apparently healthy patient as a premonitory sign of occult cancer ' (1986 ) 57 Cancer : 1846 -1849.

    • Search Google Scholar
  • Hettiarachchi, R. J. K., Prins, M. H., Lok, I. et al.: Undiagnosed malignancy in patients with deep vein thrombosis. Incidence, risk indicators, and diagnosis. Cancer, 1998, 83 , 180–185.

    Lok I. , 'Undiagnosed malignancy in patients with deep vein thrombosis. Incidence, risk indicators, and diagnosis ' (1998 ) 83 Cancer : 180 -185.

    • Search Google Scholar
  • Rajan, R., Levine, M., Gent, M. et al.: The occurrence of subsequent malignancy in patients presenting with deep vein thrombosis: result from a historical cohort study. Thromb. Haemost., 1998, 79 , 19–22.

    Gent M. , 'The occurrence of subsequent malignancy in patients presenting with deep vein thrombosis: result from a historical cohort study ' (1998 ) 79 Thromb. Haemost. : 19 -22.

    • Search Google Scholar
  • Boda, Z.: Diffuse intravascular coagulation (DIC). In Boda, Z., Rák, K., Udvardy, M. (eds): Clinical Haemostaseologie. Springer Verlag, Berlin, 1999, 194–201.

    Boda Z. , '', in Clinical Haemostaseologie , (1999 ) -.

  • Colman, R. W., Rubin, R. N.: Disseminated intravascular coagulation due to malignancy. Semin. Oncol., 1990, 17 , 172–186.

    Rubin R. N. , 'Disseminated intravascular coagulation due to malignancy ' (1990 ) 17 Semin. Oncol. : 172 -186.

    • Search Google Scholar
  • Deppisch, L. M., Fayemi, A. O.: Nonbacterial thrombotic endocarditis: clinicopathologic correlations. Am. Heart J., 1976, 92 , 723–729.

    Fayemi A. O. , 'Nonbacterial thrombotic endocarditis: clinicopathologic correlations ' (1976 ) 92 Am. Heart J. : 723 -729.

    • Search Google Scholar
  • Lesesne, I. B., Rothschild, N., Erickson, B. et al.: Cancer-associated hemolytic-uremic syndrome: analysis of 85 cases from a national registry. J. Clin. Oncol., 1989, 7 , 781–789.

    Erickson B. , 'Cancer-associated hemolytic-uremic syndrome: analysis of 85 cases from a national registry ' (1989 ) 7 J. Clin. Oncol. : 781 -789.

    • Search Google Scholar
  • Gordon, S. G.: Tumor cell procoagulants and their role in malignant disease. Semin. Thromb. Hemost., 1992, 18 , 424–433.

    Gordon S. G. , 'Tumor cell procoagulants and their role in malignant disease ' (1992 ) 18 Semin. Thromb. Hemost. : 424 -433.

    • Search Google Scholar
  • Francis, I. L., Biggerstaff, J., Amirkhosravi, A.: Haemostasis and malignancy. Semin. Thromb. Hemost., 1998, 24 , 93–108.

    Amirkhosravi A. , 'Haemostasis and malignancy ' (1998 ) 24 Semin. Thromb. Hemost. : 93 -108.

  • Sallah, S., Wan, I. Y., Nguyen, N. P.: Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb. Haemost., 2002, 87 , 575–579.

    Nguyen N. P. , 'Venous thrombosis in patients with solid tumors: determination of frequency and characteristics ' (2002 ) 87 Thromb. Haemost. : 575 -579.

    • Search Google Scholar
  • Felding-Habermann, B.: Tumor cell-platelet interaction in metastatic disease. Haemostasis, 2001, 31 (Suppl. 1) , 55–58.

    Felding-Habermann B. , 'Tumor cell-platelet interaction in metastatic disease ' (2001 ) 31 Haemostasis : 55 -58.

    • Search Google Scholar
  • Kwaan, H. C., Keer, H. N.: Fibrinolysis and cancer. Semin. Thromb. Hemost., 1990, 16 , 230–235.

    Keer H. N. , 'Fibrinolysis and cancer ' (1990 ) 16 Semin. Thromb. Hemost. : 230 -235.

  • Illtyd, J., Matheson, N. M.: Thrombophlebitis in cancer. Practitioner, 1935, 134 , 683–684.

    Matheson N. M. , 'Thrombophlebitis in cancer ' (1935 ) 134 Practitioner : 683 -684.

  • Gore, J. M., Appelbaum, J. S., Greene, H. L. et al.: Occult cancer in patients with acute pulmonary embolism. Ann. Intern. Med., 1982, 96 , 556–560.

    Greene H. L. , 'Occult cancer in patients with acute pulmonary embolism ' (1982 ) 96 Ann. Intern. Med. : 556 -560.

    • Search Google Scholar
  • Bastonnis, E. A., Karayiannakis, A. J., Makri, G. G. et al.: The incidence of occult cancer in patients with deep venous thrombosis: a prospective study. J. Intern. Med., 1996, 239 , 153–156.

    Makri G. G. , 'The incidence of occult cancer in patients with deep venous thrombosis: a prospective study ' (1996 ) 239 J. Intern. Med. : 153 -156.

    • Search Google Scholar
  • Montreal, M., Fernandez-Llamazares, J., Perandreu, J. et al.: Occult cancer in patients with venous thromboembolism: Which patients, which cancers. Thromb. Haemost., 1997, 78 , 1316–1322.

    Perandreu J. , 'Occult cancer in patients with venous thromboembolism: Which patients, which cancers ' (1997 ) 78 Thromb. Haemost. : 1316 -1322.

    • Search Google Scholar
  • Piccioli, A., Lensing, A. W. A., Prins, M. H. et al.: Extensive screening for occult malignant disease in idiopathic venous thromboembolism. Pathophysiol. Haemost. Thromb., 2002, 32 (Suppl.) , 50–57.

    Prins M. H. , 'Extensive screening for occult malignant disease in idiopathic venous thromboembolism ' (2002 ) 32 Pathophysiol. Haemost. Thromb. : 50 -57.

    • Search Google Scholar
  • Sorensen, H. T., Mellemkjaer, L., Steffensen, F. H. et al.: The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism. N. Eng. J. Med., 1998, 338 , 1169–1173.

    Steffensen F. H. , 'The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism ' (1998 ) 338 N. Eng. J. Med. : 1169 -1173.

    • Search Google Scholar
  • Hirsch, J., Lee, A. Y.: How we diagnose and treat deep vein thrombosis. Blood, 2002, 99 , 3102–3110.

    Lee A. Y. , 'How we diagnose and treat deep vein thrombosis ' (2002 ) 99 Blood : 3102 -3110.

  • Lee, A. Y., Julian, J. A., Levine, M. N. et al.: Clinical utility of a rapid whole blood D-dimer assay in patients with cancer who present with suspected acute deep venous thrombosis. Ann. Intern. Med., 1999, 131 , 417–423.

    Levine M. N. , 'Clinical utility of a rapid whole blood D-dimer assay in patients with cancer who present with suspected acute deep venous thrombosis ' (1999 ) 131 Ann. Intern. Med. : 417 -423.

    • Search Google Scholar
  • Miceli, M., Atoni, R., Walker, R. et al.: Diagnosis of deep septic thrombophlebitis in cancer patients by fluorine-18 fluordeoxyglucose positron emission tomography scanning: a preliminary report. J. Clin. Oncol., 2004, 22 , 1949–1956.

    Walker R. , 'Diagnosis of deep septic thrombophlebitis in cancer patients by fluorine-18 fluordeoxyglucose positron emission tomography scanning: a preliminary report ' (2004 ) 22 J. Clin. Oncol. : 1949 -1956.

    • Search Google Scholar
  • George, I. N.: Thrombotic thrombocytopenic purpura. N. Eng. J. Med., 2006, 354 , 1927–1935.

    George I. N. , 'Thrombotic thrombocytopenic purpura ' (2006 ) 354 N. Eng. J. Med. : 1927 -1935.

    • Search Google Scholar
  • Heit, I. A., Silverstein, M. D., Mohr, D. N. et al.: Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch. Intern. Med., 1999, 159 , 445–453.

    Mohr D. N. , 'Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based cohort study ' (1999 ) 159 Arch. Intern. Med. : 445 -453.

    • Search Google Scholar