Hypercoagulability in patients with haematological neoplasia: No apparent initiation by tissue factor

Helene F. S. Negaard; Per Ole Iversen; Bjørn Østenstad; Nina Iversen; Pål A. Holme; Per Morten Sandset

doi:10.1160/TH07-09-0541

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 99(06): 1040-1048
DOI: 10.1160/TH07-09-0541

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Hypercoagulability in patients with haematological neoplasia: No apparent initiation by tissue factor

Authors

Helene F. S. Negaard

¹Departments of Haematology

⁴Faculty of Medicine, University of Oslo, Norway
Per Ole Iversen

¹Departments of Haematology

⁴Faculty of Medicine, University of Oslo, Norway
Bjørn Østenstad

²Oncology, and
Nina Iversen

³Medical Genetics, Ullevål University Hospital Trust, Oslo, Norway
Pål A. Holme

⁵Department of Haematology, Rikshospitalet UNiversity Hospital Trust, Oslo, Norway
Per Morten Sandset

¹Departments of Haematology

⁴Faculty of Medicine, University of Oslo, Norway

Abstract

Summary

Patients with haematological malignancies carry increased risk of venous thrombosis (VT). However, the mechanisms that link these malignancies to activated coagulation have not been fully identified. Since anti-haemostatic agents are studied in clinical trials for their potential to prolong survival in cancer patients, a detailed characterisation of haemostatic markers in cancer subtypes is needed. Hence, in this study, we measured the plasma concentrations and mRNA expression in blood mononuclear cells of haemostatic parameters in 93 patients with haematological neoplasias (acute myeloid leukaemia, chronic lymphatic leukaemia, multiple myeloma, and non-Hodgkin’s lymphoma) before start and after completion of cancer therapy. At diagnosis we found activation of coagulation and fibrinolysis, especially in patients with acute myeloid leukaemia. This hypercoagulation was not associated with increased levels of tissue factor (TF) or factor VII (fVII) antigen or mRNA, or levels of activated fVII. In conclusion we found a hypercoagulable state in patients with haematological malignancy that did not seem to be initiated by TF.

Keywords

Coagulation - leukaemia - lymphoma - myeloma - tissue factor

Full Text

References

References
1 Blom JW, Doggen CJM, Osanto S. et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. J Am Med Asoc 2005; 293: 715-722.
2 Sorensen HT, Mellemkjaer L, Olsen JH. et al. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000; 343: 1846-1850.
3 Pruemer J.. Prevalence, causes, and impact of cancer-associated thrombosis. Am J Health Syst Pharm 2005; 62: S4-S6.
4 Caine GJ, Stonelake PS, Lip GYH. et al. The hypercoagulable state of malignancy: Pathogenesis and current debate. Neoplasia 2002; 4: 465-473.
5 Rickles FR, Patierno SR, Fernandez PM.. Tissue factor, thrombin and cancer. Chest 2003; 124: 58S-68S.
6 Monroe DM, Hoffman M. What does it take to make the perfect clot?. Arterioscler Thromb Vasc Biol 2006; 26: 41-48.
7 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: 54-57.
8 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: 209-215.
9 Nadir Y, Katz T, Sarig G. et al. Hemostatic balance on the surface of leukemic cells: the role of tissue factor and urokinase plasminogen activator receptor. Haematologia (Budap) 2005; 90: 1549-1556.
10 Sase T, Wada H, Yamaguchi M. et al. Haemostatic abnormalities and thrombotic disorders in malignant lymphoma. Thromb Haemost 2005; 93: 153-159.
11 Zhang Y, Deng Y, Luther T. et al. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumour cells in mice. J Clin Invest 1994; 94: 1320-1327.
12 Wang Z, Wang M, Amarzguioui M. et al. Downregulation of Tissue Factor by RNA interferences in human melanoma LOX-L cells reduces pulmonary metastasis in nude mice. Int J Cancer 2004; 112: 994-1002.
13 Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. The Lancet Oncology 2005; 6: 401-410.
14 Sanz MA, Jarque I, Martin G. et al. Acute promyelocytic leukemia. Therapy results and prognostic factors. Cancer 1988; 61: 7-13.
15 Bennet JM, Catovsky D, Daniel MT. et al. Proposed revised criteria for the classification of acute myeloid leukemia: a report on the French-American-British cooperative Group. Ann Intern Med 1985; 103: 620-625.
16 Oscier D, Fegan C, Hillmen P. et al. Guidelines on the diagnosis and management of chronic lymphocytic leukaemia. Br J Haematol 2004; 125: 294-317.
17 Smith A, Wisloff F, Samson D. Guidelines on the diagnosis and management of multiple myeloma 2005. Br J Haematol 2005; 132: 410-451.
18 WHO. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2001 .
19 Binet JL, Auquier A, Dighiero G. et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 1981; 48: 198-206.
20 Lister TA, Crowther D, Sutcliffe SB. et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 1989; 7: 1630-1636.
21 The Norwegian Society of Haematology. National guidelines.. Available at: http://www.legeforeningen.no/index.gan?id=11652&subid=0 Accessed 2004.
22 The Norwegian Lymphoma group. National guidelines.. Available at: http://www.legeforeningen.no/index.gan?id=67213 Accessed 2004.
23 Cheson BD, Bennett JM, Kopecky KJ. et al. Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003; 21: 4642-4649.
24 Cheson BD, Bennett JM, Grever M. et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996; 87: 4990-4997.
25 Cheson BD, Horning SJ, Coiffier B. et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol 1999; 17: 1244.
26 Taylor FB, Toh CH, Hoots WK. et al. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001; 86: 1327-1330.
27 Kirchgesser M, Adem C, Malmberg W. et al. MagNA Pure LC RNA Isolation Kit – High Performance: Maximum RNA Yield and Quality from Various Samples. Biochemica 2004; 12-13.
28 Bendz B, Andersen TO, Sandset PM. A new sensitive chromogenic substrate assay of tissue factor pathway inhibitor Type 1. Thromb Res 2000; 97: 463-472.
29 Adam M, Vauthier C, Morrissey JH, Woodhams BJ. Assay development for plasma factor VIIa-antithrombin complex (fVIIa-AT). J Thromb Haemost 2007; (Suppl. 02) P-S-111.
30 Exner T, Joseph J, Low J. et al. A new activated factor X-based clotting method with improved specificity for procoagulant phospholipid. Blood Coagul Fibrinolysis 2003; 14: 773-779.
31 Applied Biosystems. Relative quantification of gene expression. ABI Prism 7700 Sequence Detection System. User Bulletin No.2.. 1997 .
32 Chojnowski K, Wawrzyniak E, Trelinski J. et al. Assessment of coagulation disorders in patients with acute leukemia before and after cytostatic treatment. Leuk Lymphoma 1999; 36: 77-84.
33 Sase T, Wada H, Kamikura Y. et al. Tissue factor messenger RNA levels in leukocytes compared with tissue factor antigens in plasma from patients in hypercoagulable state caused by various diseases. Thromb Haemost 2004; 92: 132-139.
34 Rao LV, Rapaport SI, Hoang AD. Binding of factor VIIa to tissue factor permits rapid antithrombin III/heparin inhibition of factor VIIa. Blood 1993; 81: 2600-2607.
35 Hair GA, Padula S, Zeff R. et al. Tissue factor expression in human leukemic cells. Leuk Res 1996; 20: 1-11.
36 Langer F, Amirkhosravi A, Loges S. et al. An in vitro study on the mechanisms of coagulation activation in acute myelogenous leukemia (AML): role of tissue factor regulation by cytotoxic drugs and GMCSF. Thromb Haemost 2004; 92: 1136-1146.
37 Collins SJ, Gallo RC, Gallagher RE. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature 1977; 270: 347-349.
38 Kamikura Y, Wada H, Sase T. et al. Hemostatic abnormalities and leukocyte activation caused by infection in patients with malignant lymphoma during chemotherapy. Thromb Res 2006; 117: 671-679.
39 Tanaka M, Yamanishi H. The expression of tissue factor antigen and activity on the surface of leukemic cells. Leuk Res 1993; 17: 103-111.
40 Carr JM, Dvorak AM, Dvorak HF. Circulating membrane vesicles in leukemic blood. Cancer Res 1985; 45: 5944-5951.
41 Lwaleed BA, Cooper AJ, Voegeli D. et al. Tissue factor: A critical role in inflammation and cancer. Biol Res Nurs 2007; 9: 97-107.
42 Bach R, Rifkin DB. Expression of tissue factor procoagulant activity: Regulation by cytosolic calcium. PNAS 1990; 87: 6995-6999.
43 Eilertsen KE, Osterud B. Tissue factor: (patho)physiology and cellular biology. Blood Coagul Fibrinolysis 2004; 15: 521-538.
44 Sandset PM, Warn-Cramer BJ, Rao VM. et al. Depletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation induced with tissue factor: Evidence supporting a physiologic role for EPI as a natural anticoagulant. Proc Natl Acad Sci USA 1991; 88: 708-712.
45 Dahm A, Vlieg AH, Bendz B. et al. Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis. Blood 2003; 101: 4387-4392.
46 Radziwon P, Schenk JF, Mazgajska K. et al. Tissue factor (TF) and inhibitor (TFPI) concentrations in patients with urinary tract tumors and haematological malignancies. Pol Merkur Lekarski 2002; 13: 308-311.
47 Iversen N, Lindahl AK, Abildgaard U. Elevated TFPI in malignant disease: relation to cancer type and hypercoagulation. Br J Haematol 1998; 102: 889-895.