Microparticle-associated tissue factor activity and venous thrombosis in multiple myeloma

Johannes J. A. Auwerda; Yuana Yuana; Susanne Osanto; Moniek P. M. de Maat; Pieter Sonneveld; Rogier M. Bertina; Frank W. G. Leebeek

doi:10.1160/TH10-03-0187

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 105(01): 14-20
DOI: 10.1160/TH10-03-0187

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Microparticle-associated tissue factor activity and venous thrombosis in multiple myeloma

Authors

Johannes J. A. Auwerda

¹Department of Hematology, Erasmus University Medical Center Rotterdam, the Netherlands
Yuana Yuana

²Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands
Susanne Osanto

²Department of Clinical Oncology, Leiden University Medical Center, Leiden, the Netherlands
Moniek P. M. de Maat

¹Department of Hematology, Erasmus University Medical Center Rotterdam, the Netherlands
Pieter Sonneveld

¹Department of Hematology, Erasmus University Medical Center Rotterdam, the Netherlands
Rogier M. Bertina

³Einthoven Laboratory for Experimental Vascular Medicine, Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands
Frank W. G. Leebeek

¹Department of Hematology, Erasmus University Medical Center Rotterdam, the Netherlands

Abstract

Summary

Multiple myeloma (MM) is associated with an increased risk of venous thromboembolic (VTE) complications. Aim of this study was to measure microparticle-associated tissue factor (MP-TF) activity in patients with newly diagnosed MM before and after chemotherapy and to investigate whether MP-TF activity is associated with VTE. MP-TF activity was assessed in 122 newly diagnosed MM patients who were eligible for combination chemotherapy. MP-TF activity levels (17.6 fM Xa/min [8.6–33.2] (median [IQR]) were higher in untreated MM patients compared to normal healthy volunteers (4.1 fM Xa/min [2.3–6.6], p <0.001). MP-TF activity prior to the start of treatment was not different between patients who developed a VTE during follow-up (n=15) and those who did not (n=107). In 75 patients in whom plasma was obtained before and after chemotherapy, MP-TF activity decreased significantly (from 17.4 [10.2–32.8] to 12.0 [7.0–18.5] fM Xa/min, P=0.006). MP-TF activity remained, however, elevated in patients who developed VTE (15.1 [10.3–25.2]), in contrast to patients not developing VTE (11.4 [7.0–25.2], P<0.001). In conclusion, MP-TF activity is increased in patients with MM. Whether MP-TF activity has a pathogenetic role in VTE in MM patients remains to be established in future studies.

Keywords

Multiple myeloma - tissue factor - microparticles - venous thrombosis

Full Text

References

References
1 Zangari M, Elice F, Fink L. et al. Thrombosis in multiple myeloma. Expert Rev Anticancer Ther 2007; 07: 307-315.
2 Palumbo A, Rajkumar SV, Dimopoulos MA. et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 2008; 22: 414-423.
3 Auwerda JJ, Sonneveld P, de Maat MP. et al. Prothrombotic coagulation abnormalities in patients with newly diagnosed multiple myeloma. Haematologica 2007; 92: 279-280.
4 Minnema MC, Fijnheer R, De Groot PG. et al. Extremely high levels of von Wille-brand factor antigen and of procoagulant factor VIII found in multiple myeloma patients are associated with activity status but not with thalidomide treatment. J Thromb Haemost 2003; 01: 445-449.
5 Elice F, Fink L, Tricot G. et al. Acquired resistance to activated protein C (aAPCR) in multiple myeloma is a transitory abnormality associated with an increased risk of venous thromboembolism. Br J Haematol 2006; 134: 399-405.
6 van Marion AM, Auwerda JJ, Minnema MC. et al. Hypofibrinolysis during induction treatment of multiple myeloma may increase the risk of venous thrombosis. Thromb Haemost 2005; 94: 1341-1343.
7 Jimenez VHs, Dominguez VJs. Acquired activated protein C resistance and thrombosis in multiple myeloma patients. Thromb J 2006; 04: 11.
8 Giesen PL, Rauch U, Bohrmann B. et al. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA 1999; 96: 2311-2315.
9 Morel O, Toti F, Hugel B. et al. Cellular microparticles: a disseminated storage pool of bioactive vascular effectors. Curr Opin Hematol 2004; 11: 156-164.
10 Kakkar AK, Lemoine NR, Scully MF. et al. Tissue factor expression correlates with histological grade in human pancreatic cancer. Br J Surg 1995; 82: 1101-1104.
11 Uno K, Homma S, Satoh T. et al. Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer. Br J Cancer 2007; 96: 290-295.
12 Wojtukiewicz MZ, Sierko E, Klement P. et al. The hemostatic system and angio-genesis in malignancy. Neoplasia 2001; 03: 371-384.
13 Khorana AA, Ahrendt SA, Ryan CK. et al. Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer. Clin Cancer Res 2007; 13: 2870-2875.
14 Tesselaar ME, Romijn FP, Van Der Linden IK. et al. Microparticle-associated tissue factor activity: a link between cancer and thrombosis?. J Thromb Haemost 2007; 05: 520-527.
15 Manly DA, Wang J, Glover SL. et al. Increased microparticle tissue factor activity in cancer patients with Venous Thromboembolism. Thromb Res 2010; 125: 511-512.
16 Zwicker JI, Liebman HA, Neuberg D. et al. Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res 2009; 15: 6830-6840.
17 Toth B, Liebhardt S, Steinig K. et al. Platelet-derived microparticles and coagulation activation in breast cancer patients. Thromb Haemost 2008; 100: 663-669.
18 Zwicker JI. Predictive value of tissue factor bearing microparticles in cancer associated thrombosis. Thromb Res 2010; 125 (Suppl. 02) S89-91.
19 Khorana AA, Francis CW, Menzies KE. et al. Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer. J Thromb Haemost 2008; 06: 1983-1985.
20 Tesselaar ME, Osanto S. Risk of venous thromboembolism in lung cancer. Curr Opin Pulm Med 2007; 13: 362-367.
21 Hron G, Kollars M, Weber H. et al. Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer. Thromb Haemost 2007; 97: 119-123.
22 Kyle RA. Diagnostic criteria of multiple myeloma. Hematol Oncol Clin North Am 1992; 06: 347-358.
23 Greipp PR, San Miguel J, Durie BG. et al. International staging system for multiple myeloma. J Clin Oncol 2005; 23: 3412-3420.
24 Durie BG, Salmon SE. Cellular kinetics staging, and immunoglobulin synthesis in multiple myeloma. Annu Rev Med 1975; 26: 283-288.
25 Vanwijk MJ, Svedas E, Boer K. et al. Isolated microparticles, but not whole plasma, from women with preeclampsia impair endothelium-dependent relaxation in isolated myometrial arteries from healthy pregnant women. Am J Obstet Gynecol 2002; 187: 1686-1693.
26 Rickles FR, Patierno S, Fernandez PM. Tissue factor, thrombin, and cancer. Chest 2003; 124 (Suppl. 03) 58S-68S.
27 Mueller BM, Reisfeld RA, Edgington TS. et al. Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis. Proc Natl Acad Sci USA 1992; 89: 11832-11836.
28 Kakkar AK, DeRuvo N, Chinswangwatanakul V. et al. Extrinsic-pathway activation in cancer with high factor VIIa and tissue factor. Lancet 1995; 346: 1004-1005.
29 Sase T, Wada H, Yamaguchi M. et al. Haemostatic abnormalities and thrombotic disorders in malignant lymphoma. Thromb Haemost 2005; 93: 153-159.
30 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 hyper-coagulable state caused by various diseases. Thromb Haemost 2004; 92: 132-139.
31 Negaard HF, Iversen PO, Ostenstad B. et al. Hypercoagulability in patients with haematological neoplasia: No apparent initiation by tissue factor. Thromb Haemost 2008; 99: 1040-1048.
32 Shimizu K, Itoh J. A possible link between Trousseau‘s syndrome and tissue factor producing plasma cells. Am J Hematol 2009; 84: 382-385.
33 Key NS, Chantrathammachart P, Moody PW. et al. Membrane microparticles in VTE and cancer. Thromb Res 2010; 125 (Suppl. 02) S80-83.
34 Palumbo A, Bringhen S, Caravita T. et al. Oral melphalan and prednisone chemo-therapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 2006; 367: 825-831.
35 Zangari M, Barlogie B, Anaissie E. et al. Deep vein thrombosis in patients with multiple myeloma treated with thalidomide and chemotherapy: effects of prophylactic and therapeutic anticoagulation. Br J Haematol 2004; 126: 715-721.
36 Hussein MA. Thromboembolism risk reduction in multiple myeloma patients treated with immunomodulatory drug combinations. Thromb Haemost 2006; 95: 924-930.
37 Zangari M, Barlogie B, Thertulien R. et al. Thalidomide and deep vein thrombosis in multiple myeloma: risk factors and effect on survival. Clin Lymphoma 2003; 04: 32-35.

Supplementary Material

Online Supplementary Material (PDF) (PDF)