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Thromb Haemost 2005; 93(01): 153-159
DOI: 10.1160/TH04-04-0260
DOI: 10.1160/TH04-04-0260
Cellular Proteolysis and Oncology
Haemostatic abnormalities and thrombotic disorders in malignant lymphoma
Further Information
Correspondence to:
Hideo Wada, MD
Department of Laboratory Medicine
Mie University School of Medicine
2–174 Edobashi, Tsu
Mie 514–8507, Japan
Phone: +81–59–232–1111 (ext. 5391)
Fax: +81–59–231–5204
Publication History
Received
27 April 2004
Accepted after resubmission
19 October 2004
Publication Date:
14 December 2017 (online)
Summary
We examined haemostatic abnormalities and thrombotic disorders in 217 patients with malignant lymphoma. Plasma levels of fibrinogen and D-dimer were significantly higher in patients with malignant lymphoma than in healthy subjects.The incidence of severe complications, such as disseminated intravascular coagulation (DIC) and interstitial pneumonia (IP), differed with each clinical stage or histological type, but they occurred frequently in stage IV or natural killer (NK) cell lymphoma. Plasma levels of fibrinogen degradation products (FDP) and D-dimer, leukocyte tissue factor (TF) mRNA and plasma TF antigen were significantly higher in stage IV than in stage I, II or III. Plasma levels of FDP, D-dimer, and leukocyte TF mRNA in NK cell lymp homa were markedly higher than in other types of lymphoma. Immunohistochemical staining of NK cell lymphoma revealed that granulocyte macrophage colony-stimulating factor was positive in tumour cells, whereas von Willebrand factor and TF were positive in vascular endothelial cells of surrounding tissue. Our results suggested that patients with stage IV disease and NK cell lymphoma were in abnormal thrombotic and haemostatic state, and may frequently develop DIC and IP. One of the mechanisms of DIC and IP may involve elevated cytokine production by lymphoma cells, which can stimulate the expression of TF in blood cells or surrounding tissue.
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Keywords
Malignant lymphoma - disseminated intravascular coagulation - interstitial pneumonia - thrombotic diseases - leukocyte tissue factor
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References
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- 2 Pasquini E, Gianni L, Aitini E. et al Acute disseminated intravascular coagulation syndrome in cancer patients. Oncology 1995; 52: 505-8.
- 3 Sallah S, Wan JY, Nguyen NP. Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost 2002; 87: 575-9.
- 4 Nakasaki T, Wada H, Mori Y. et al Decreased tissue factor and tissue-plasminogen activator antigen in relapsed acute promyelocytic leukemia. Am J Hematol 2000; 64: 145-50.
- 5 Goldschmidt N, Linetsky E, Shalom E. et al High incidence of thromboembolism in patients with central nervous system lymphoma. Cancer 2003; 98: 1239-42.
- 6 Sutherland DE, Weitz IC, Liebman HA. Thromboembolic complications of cancer: epidemiology, pathogenesis, diagnosis, and treatment. Am J Hematol 2003; 72: 43-52.
- 7 Lip GY, Chin BS, Blann AD. Cancer and the prothrombotic state. Lancet Oncology 2002; 3: 27-34.
- 8 Dasmahapatra KS, Cheung NK, Spillert C. et al An assessment of monocyte procoagulant activity in patients with solid tumors. J Surg Res 1987; 43: 158-63.
- 9 Callander NS, Varki N, Rao LV. Immunohistochemical identification of tissue factor in solid tumors. Cancer 1992; 70: 1194-201.
- 10 Wojtukiewicz MZ, Sierko E, Zacharski LR. et al Tissue factor dependent coagulation and impaired fibrinolysis in situ in gastric cancer. Semin Thromb Hemost 2003; 29: 291-300.
- 11 Nemerson Y, Bach R. Tissue factor revisited. Prog Haemostasis Thromb 1982; 6: 237-61.
- 12 Contrino J, Hair G, Kreutzer DL. et al In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast disease. Nat Med 1996; 2: 209-15.
- 13 Rickles FR. Relationship of blood clotting and tumor angiogenesis. Haemostasis 2001; 31: 16-20.
- 14 Femandez PM, Patierno SR, Rickles FR. Tissue factor and fibrin in tumor angiogenesis. Semin Thromb Haemost 2004; 30: 31-44.
- 15 Hjortoe GM, Petersen LC, Albrektsen T. et al Tissue factor-factor VIIa specific upregulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration. Blood 2004; 103: 3029-37.
- 16 Shigemori C, Wada H, Matsumoto K. et al Tissue factor expression and metastatic potential of colorectal cancer. Thromb Haemost 1998; 80: 894-8.
- 17 Koyama T, Nishida K, Ohdama S. et al Determination of plasma tissue factor antigen and its clinical significance. Br J Haematol 1994; 87: 343-7.
- 18 Dorfleutner A, Ruf W. Regulation of tissue factor cytoplasmic domain phosphorylation by palmitoylation. Blood 2003; 102: 3998-4005.
- 19 Spek CA. Tissue factor: from just one of the coagulation factor to a major player in physiology. Blood Coagul Fibrinolysis 2004; 15: 3-10.
- 20 Wada H, Nakase T, Nakaya R. et al Elevated plasma tissue factor antigen level in patients with disseminated intravascular coagulation. Am J Hematol 1994; 45: 232-6.
- 21 Sase T, Wada H, Nishiokka J. et al Measurement of tissue factor messenger RNA levels in leukocytes from patients in hypercoagulable state caused by several underlying diseases. Thromb Haemost 2003; 89: 660-5.
- 22 Wada H, Ohiwa M, Kaneko T. et al Plasma level of tumor necrosis factor in disseminated intravascular coagulation. Am J Hematol 1991; 37: 147-51.
- 23 Wada H, Tamaki S, Tanigawa M. et al Plasma level of IL-1® in disseminated intravascular coagulation. Thromb Haemost 1991; 65: 364-8.
- 24 Franco RF, de Jonge E, Dekkers PE. et al The in vivo kinetics of tissue factor messenger RNA expression during human endotoxemia: relationship with activation of coagulation. Blood 2000; 96: 554-9.
- 25 McNally RJ, Roman E, Cartwright RA. Leukemias and lymphomas: time trends in the UK, 1984–93. Cancer Causes Control 1999; 10: 35-42.
- 26 Bick RL, Strauss JF, Frenkel EP. Thrombosis and hemorrhage in oncology patients. Hematol Oncol North Am 1996; 10: 875-907.
- 27 Esmon CT. Role of coagulation inhibitors in inflammation. Thromb Haemost 2001; 86: 51-6.
- 28 Harris NL, Jaffe ES, Stein H. A revised European- American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994; 84: 1361-92.
- 29 Imamura T, Kaneda H, Nakamura S. New functions of neutrophils in the arthus reaction: Expression of tissue factor, the clotting initiator, and fibrinolysis by elastase. Lab Invest 2002; 82: 1287-95.
- 30 Mensink E, van de Locht, Schattenberg A. et al Quantitation of minimal residual disease in Philadelphia chromosome positive chronic myeloid leukemia patients using real time quantitative RT-PCR. Br J Hematol 1998; 102: 768-74.
- 31 Taylor Jr F, Toh CH, Hoots K. et al Towards definition clinical and laboratory criteria and a scoring system for disseminated intravascular coagulation. On behalf of the Scientific Subcommittee on disseminated intravascular coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Thromb Haemost 2001; 86: 1327-30.
- 32 Gouin-Thibault I, Achkar A, Samama MM. The thrombophilic state in cancer patients. Acta Haematol 2001; 106: 33-42.
- 33 Levi M. Cancer and DIC. Haemostasis 2001; 31: 47-8.
- 34 Di Micco P, Romano M, Niglio A. et al Alteration of haemostasis in non-metastatic gastric cancer. Dig Liver Dis 2001; 33: 546-50.
- 35 Palumbo JS, Kombrinck KW, Drew AF. et al Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells. Blood 2000; 15: 3302-9.
- 36 Dirix LY, Salgado R, Weytjens R. et al Plasma fibrin D-dimer levels correlate with tumor volume, progression rate and survival in patients with metastatic breast cancer. Br J Cancer 2002; 86: 389-95.
- 37 Kohli M, Fink LM, Spencer HJ. et al Advanced prostate cancer activates coagulation: a controlled study of activation makers of coagulation in ambulatory patients with localized and advanced prostate cancer. Blood Coagul Fibrinolysis 2002; 13: 1-5.
- 38 Semeraro N, Montemurro P, Giordano P. et al Increased mononuclear cell tissue factor and type-2 plasminogen activator inhibitor and reduced plasma fibrinolytic capacity in children with lymphoma. Thromb Haemost 1994; 72: 54-7.
- 39 Cushman M, Folsom AR, Heckbert SR. Fibrin fragment D-dimer and the risk of future venous thrombosis. Blood 2003; 101: 1243-8.
- 40 Sallah S, Wan JY, Sigounas G. Disseminated intravascular coagulation in solid tumors: clinical and pathologic study. Thromb Haemost 2001; 86: 828-33.
- 41 Wada H, Nagano T, Tomeoku M. et al Coagulation and fibrinolytic activities in the leukemic cell lysates. Thromb Res 1982; 30: 315-22.
- 42 Nakasaki T, Wada H, Watanabe R. et al Elevated tissue factor levels in leukemic cell homogenate. Clin Appl Thromb Haemost 2000; 6: 14-7.
- 43 Nakasaki T, Wada H, Shigemori C. et al Expression of tissue factor and vascular endothelial growth factor is associated with angiogenesis in colorectal cancer. Am J Hematol 2002; 69: 247-54.
- 44 Salgado A, Boveda J, Monasterio J. et al Inflammatory mediators and their influence on haemostasis. Haemostasis 1994; 24: 132-8.
- 45 Gregory SA, Morrissey JH, Edgington TS. Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin. Mol Cell Biol 1989; 9: 2752-5.
- 46 Imokawa S, Sato A, Hayakawa H. et al Tissue factor expression and fibrin deposition in the lungs of patients with idiopathic pulmonary fibrosis and systemic sclerosis. Am J Respir Crit Care Med 1997; 156: 631-6.
- 47 Gunther A, Mosavi P, Ruppert C. et al Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease. Thromb Haemost 2000; 83: 853-60.
- 48 Idell S, Gonzalez K, Bradford H. et al Procoagulant activity in bronchoalveolar lavage in the adult respiratory distress syndrome. Contribution of tissue factor associated with factor VII. Am Rev Respir 1987; 136: 1466-74.
- 49 Kotani I, Sato A, Takada A. Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis. Thromb Res 1995; 77: 494-504.
- 50 Weitz IC, Israel VK, Waisman JR. et al Chemotherapy- induced activation of haemostasis: effect of a low molecular weight heparin (daiteparin sodium) on plasma makers of haemostatic activation. Thromb Haemost 2002; 88: 213-20.
- 51 Berkani K, Bayle JY, Perol M. et al "Spontaneous" resolution of two severe methotrexate-induced pneumonias. Rev Pneumol Clin 2003; 59: 301-5.
- 52 Jullien V, Perrin C, Peyrade F. et al A case of acute respiratory failure related to rituximab therapy. Rev Mal Respir 2004; 21: 407-10.
- 53 Nitsu N, Iki S, Muroi K. et al Interstitial pneumonia in patients receiving granulocyte colony-stimulating factor during chemotherapy: survey in Japan 1991–96. Br J Cancer 1997; 76: 1661-6.
Correspondence to:
Hideo Wada, MD
Department of Laboratory Medicine
Mie University School of Medicine
2–174 Edobashi, Tsu
Mie 514–8507, Japan
Phone: +81–59–232–1111 (ext. 5391)
Fax: +81–59–231–5204
-
References
- 1 Donati MB. Cancer and thrombosis: from phlegmasia alba dolens to transgenic mice. Thromb Haemost 1995; 74: 278-81.
- 2 Pasquini E, Gianni L, Aitini E. et al Acute disseminated intravascular coagulation syndrome in cancer patients. Oncology 1995; 52: 505-8.
- 3 Sallah S, Wan JY, Nguyen NP. Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost 2002; 87: 575-9.
- 4 Nakasaki T, Wada H, Mori Y. et al Decreased tissue factor and tissue-plasminogen activator antigen in relapsed acute promyelocytic leukemia. Am J Hematol 2000; 64: 145-50.
- 5 Goldschmidt N, Linetsky E, Shalom E. et al High incidence of thromboembolism in patients with central nervous system lymphoma. Cancer 2003; 98: 1239-42.
- 6 Sutherland DE, Weitz IC, Liebman HA. Thromboembolic complications of cancer: epidemiology, pathogenesis, diagnosis, and treatment. Am J Hematol 2003; 72: 43-52.
- 7 Lip GY, Chin BS, Blann AD. Cancer and the prothrombotic state. Lancet Oncology 2002; 3: 27-34.
- 8 Dasmahapatra KS, Cheung NK, Spillert C. et al An assessment of monocyte procoagulant activity in patients with solid tumors. J Surg Res 1987; 43: 158-63.
- 9 Callander NS, Varki N, Rao LV. Immunohistochemical identification of tissue factor in solid tumors. Cancer 1992; 70: 1194-201.
- 10 Wojtukiewicz MZ, Sierko E, Zacharski LR. et al Tissue factor dependent coagulation and impaired fibrinolysis in situ in gastric cancer. Semin Thromb Hemost 2003; 29: 291-300.
- 11 Nemerson Y, Bach R. Tissue factor revisited. Prog Haemostasis Thromb 1982; 6: 237-61.
- 12 Contrino J, Hair G, Kreutzer DL. et al In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast disease. Nat Med 1996; 2: 209-15.
- 13 Rickles FR. Relationship of blood clotting and tumor angiogenesis. Haemostasis 2001; 31: 16-20.
- 14 Femandez PM, Patierno SR, Rickles FR. Tissue factor and fibrin in tumor angiogenesis. Semin Thromb Haemost 2004; 30: 31-44.
- 15 Hjortoe GM, Petersen LC, Albrektsen T. et al Tissue factor-factor VIIa specific upregulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration. Blood 2004; 103: 3029-37.
- 16 Shigemori C, Wada H, Matsumoto K. et al Tissue factor expression and metastatic potential of colorectal cancer. Thromb Haemost 1998; 80: 894-8.
- 17 Koyama T, Nishida K, Ohdama S. et al Determination of plasma tissue factor antigen and its clinical significance. Br J Haematol 1994; 87: 343-7.
- 18 Dorfleutner A, Ruf W. Regulation of tissue factor cytoplasmic domain phosphorylation by palmitoylation. Blood 2003; 102: 3998-4005.
- 19 Spek CA. Tissue factor: from just one of the coagulation factor to a major player in physiology. Blood Coagul Fibrinolysis 2004; 15: 3-10.
- 20 Wada H, Nakase T, Nakaya R. et al Elevated plasma tissue factor antigen level in patients with disseminated intravascular coagulation. Am J Hematol 1994; 45: 232-6.
- 21 Sase T, Wada H, Nishiokka J. et al Measurement of tissue factor messenger RNA levels in leukocytes from patients in hypercoagulable state caused by several underlying diseases. Thromb Haemost 2003; 89: 660-5.
- 22 Wada H, Ohiwa M, Kaneko T. et al Plasma level of tumor necrosis factor in disseminated intravascular coagulation. Am J Hematol 1991; 37: 147-51.
- 23 Wada H, Tamaki S, Tanigawa M. et al Plasma level of IL-1® in disseminated intravascular coagulation. Thromb Haemost 1991; 65: 364-8.
- 24 Franco RF, de Jonge E, Dekkers PE. et al The in vivo kinetics of tissue factor messenger RNA expression during human endotoxemia: relationship with activation of coagulation. Blood 2000; 96: 554-9.
- 25 McNally RJ, Roman E, Cartwright RA. Leukemias and lymphomas: time trends in the UK, 1984–93. Cancer Causes Control 1999; 10: 35-42.
- 26 Bick RL, Strauss JF, Frenkel EP. Thrombosis and hemorrhage in oncology patients. Hematol Oncol North Am 1996; 10: 875-907.
- 27 Esmon CT. Role of coagulation inhibitors in inflammation. Thromb Haemost 2001; 86: 51-6.
- 28 Harris NL, Jaffe ES, Stein H. A revised European- American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994; 84: 1361-92.
- 29 Imamura T, Kaneda H, Nakamura S. New functions of neutrophils in the arthus reaction: Expression of tissue factor, the clotting initiator, and fibrinolysis by elastase. Lab Invest 2002; 82: 1287-95.
- 30 Mensink E, van de Locht, Schattenberg A. et al Quantitation of minimal residual disease in Philadelphia chromosome positive chronic myeloid leukemia patients using real time quantitative RT-PCR. Br J Hematol 1998; 102: 768-74.
- 31 Taylor Jr F, Toh CH, Hoots K. et al Towards definition clinical and laboratory criteria and a scoring system for disseminated intravascular coagulation. On behalf of the Scientific Subcommittee on disseminated intravascular coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Thromb Haemost 2001; 86: 1327-30.
- 32 Gouin-Thibault I, Achkar A, Samama MM. The thrombophilic state in cancer patients. Acta Haematol 2001; 106: 33-42.
- 33 Levi M. Cancer and DIC. Haemostasis 2001; 31: 47-8.
- 34 Di Micco P, Romano M, Niglio A. et al Alteration of haemostasis in non-metastatic gastric cancer. Dig Liver Dis 2001; 33: 546-50.
- 35 Palumbo JS, Kombrinck KW, Drew AF. et al Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells. Blood 2000; 15: 3302-9.
- 36 Dirix LY, Salgado R, Weytjens R. et al Plasma fibrin D-dimer levels correlate with tumor volume, progression rate and survival in patients with metastatic breast cancer. Br J Cancer 2002; 86: 389-95.
- 37 Kohli M, Fink LM, Spencer HJ. et al Advanced prostate cancer activates coagulation: a controlled study of activation makers of coagulation in ambulatory patients with localized and advanced prostate cancer. Blood Coagul Fibrinolysis 2002; 13: 1-5.
- 38 Semeraro N, Montemurro P, Giordano P. et al Increased mononuclear cell tissue factor and type-2 plasminogen activator inhibitor and reduced plasma fibrinolytic capacity in children with lymphoma. Thromb Haemost 1994; 72: 54-7.
- 39 Cushman M, Folsom AR, Heckbert SR. Fibrin fragment D-dimer and the risk of future venous thrombosis. Blood 2003; 101: 1243-8.
- 40 Sallah S, Wan JY, Sigounas G. Disseminated intravascular coagulation in solid tumors: clinical and pathologic study. Thromb Haemost 2001; 86: 828-33.
- 41 Wada H, Nagano T, Tomeoku M. et al Coagulation and fibrinolytic activities in the leukemic cell lysates. Thromb Res 1982; 30: 315-22.
- 42 Nakasaki T, Wada H, Watanabe R. et al Elevated tissue factor levels in leukemic cell homogenate. Clin Appl Thromb Haemost 2000; 6: 14-7.
- 43 Nakasaki T, Wada H, Shigemori C. et al Expression of tissue factor and vascular endothelial growth factor is associated with angiogenesis in colorectal cancer. Am J Hematol 2002; 69: 247-54.
- 44 Salgado A, Boveda J, Monasterio J. et al Inflammatory mediators and their influence on haemostasis. Haemostasis 1994; 24: 132-8.
- 45 Gregory SA, Morrissey JH, Edgington TS. Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin. Mol Cell Biol 1989; 9: 2752-5.
- 46 Imokawa S, Sato A, Hayakawa H. et al Tissue factor expression and fibrin deposition in the lungs of patients with idiopathic pulmonary fibrosis and systemic sclerosis. Am J Respir Crit Care Med 1997; 156: 631-6.
- 47 Gunther A, Mosavi P, Ruppert C. et al Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease. Thromb Haemost 2000; 83: 853-60.
- 48 Idell S, Gonzalez K, Bradford H. et al Procoagulant activity in bronchoalveolar lavage in the adult respiratory distress syndrome. Contribution of tissue factor associated with factor VII. Am Rev Respir 1987; 136: 1466-74.
- 49 Kotani I, Sato A, Takada A. Increased procoagulant and antifibrinolytic activities in the lungs with idiopathic pulmonary fibrosis. Thromb Res 1995; 77: 494-504.
- 50 Weitz IC, Israel VK, Waisman JR. et al Chemotherapy- induced activation of haemostasis: effect of a low molecular weight heparin (daiteparin sodium) on plasma makers of haemostatic activation. Thromb Haemost 2002; 88: 213-20.
- 51 Berkani K, Bayle JY, Perol M. et al "Spontaneous" resolution of two severe methotrexate-induced pneumonias. Rev Pneumol Clin 2003; 59: 301-5.
- 52 Jullien V, Perrin C, Peyrade F. et al A case of acute respiratory failure related to rituximab therapy. Rev Mal Respir 2004; 21: 407-10.
- 53 Nitsu N, Iki S, Muroi K. et al Interstitial pneumonia in patients receiving granulocyte colony-stimulating factor during chemotherapy: survey in Japan 1991–96. Br J Cancer 1997; 76: 1661-6.