Measurement of tissue factor messenger RNA levels in leukocytes from patients in hypercoagulable state caused by several underlying diseases

Summary

In a preliminary study, we have demonstrated that tissue factor (TF) is immunohistochemically stained in monocytes from patients with disseminated intravascular coagulation (DIC) but not from healthy volunteers, and that leukocytes from DIC patients induce enhanced activated factor X (FXa) generation in the presence of a mixture of FVIIa, FX and Ca²⁺. Then, TF mRNA levels in leukocytes were measured to evaluate the role of TF in the pathophysiology of various diseases. TF mRNA levels in leukocytes were low in healthy volunteers but they were significantly increased in various diseases, especially in patients with infectious diseases, solid cancer, anemd hematopoietic tumors. TF mRNA levels in leukocytes were significantly higher in patients with high levels of C reactive protein (CRP) than in those with low CRP. TF mRNA levels were significantly higher in patients with DIC than in those without DIC. TF mRNA levels were well correlated with TF antigens in plasma and leukocytes. These findings suggest that the expression of TF mRNA in leukocytes is increased in various diseases and that this may play an important role in hypercoagulability or DIC.

Keywords

Tissue factor - messenger RNA - DIC - real time PCR - CRP

• References

• 1 Morrissey JH. Tissue factor: an enzyme cofactor and true receptor. Thromb Haemost 2001; 86: 66-74.
• 2 Nemerson Y. Tissue factor and hemostasis. Blood 1988; 71: 1-8.
• 3 Taylor Jr. F, Chang A, Ruf W, Morrisey JH, Hinshaw L, Catlett R, Blick K, Edington TS. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33: 127-34.
• 4 Creasey AA, Chang AC, Feigen L, Wun TC, Taylor Jr FB, Hinshaw LB. Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. J Clin Invest 1993; 91: 2850-6.
• 5 Taylor Jr FB, Chang AC, Peer G, Li A, Ezban M, Hedner U. Active site inhibited factor VIIa (DEGR VIIa) attenuates the coagulant and interleukin-6 and -8, but not tumor necrosis factor, responses of the baboon to LD 100 Escherichia coli. Blood 1998; 91: 1609-15.
• 6 Levi M, de Jonge E, van der Poll T, ten Cate H. Disseminated intravascular coagulation. Thromb Haemost 1999; 82: 695-705.
• 7 Giesen PL, Rauch U, Bohrmann B, Kling D, Roquè M, Fallon JT. et al. Blood-born tissue factor: Another view of thrombosis. Proc Natl Acad Sci USA 1999; 96: 2311-5.
• 8 Giesen PL, Nemerson Y. Tissue factor on the loose. Semin Thromb Haemost 2000; 26: 379-84.
• 9 Koyama T, Nishida K, Ohdama S, Sawada M, Murakami N, Hirosawa S. et al. Determination of plasma tissue factor antigen and its clinical significance. Br J Haematol 1994; 87: 343-7.
• 10 Wada H, Nakase T, Nakaya R, Minamikawa K, Wakita Y, Kaneko T, Ohiwa M, Deguchi K, Shirakawa S. Elevated plasma tissue factor antigen level in patients with disseminated intravascular coagulation. Am J Hematol 1994; 45: 232-6.
• 11 Zhao W, Wang H, Wang X, Wu F, Guo W, Qu B, Shen Z, Wang Z. Effects of all-trans-retinoic acid and arsenic trioxide on the hemo-static disturbance associated with acute promyelocytic leukemia. Thromb Res 2001; 102: 197-204.
• 12 Pouplard C, Iochmann S, Renard B, Herault O, Colombat P, Amiral J, Gruel Y. Induction of monocyte tissue factor expression by antibodies to heparin-platelet factor 4 complexes developed in heparin-induced thrombocytopenia. Blood 2001; 97: 3300-2.
• 13 Taylor Jr F, Toh CH, Hoots K, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. On behalf of the Scientific Subcommitee on disseminated intra-vascular coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Thromb Haemost 2001; 86: 1327-30.
• 14 Mensink E, van de Locht, Schattenberg A, Linders E, Schaap N, Geurts van Kessel A, Witte T. Quantitation of minimal residual disease in Philadelphia chromosome positive chronic myeloid leukemia patients using real-time quantitative RT-PCT. Br J Hematol 1998; 102: 768-74.
• 15 Nakamura S, Goto A, Takamoto S, Mizuguchi J, Funatsu A. Monoclonal antibodies to human tissue factor. Thromb Haemost 1991; 65: 1216 Abstract
• 16 Shigemori C, Wada H, Matsumoto K, Shiku H, Nakamura S, Suzuki H. Tissue factor expression and metastatic potential of colorectal cancer. Thromb Haemost 1998; 80: 894-8.
• 17 Wada H, Nagano T, Tomeoku M, Kuto M, Karitani Y, Deguchi K, Shirakawa S. Coagulant and fibrinolytic activities in the leukemic cell lysates. Thromb Res 1982; 30: 315-22.
• 18 Thomas JA. Toll genes and responsiveness to bacterial endotoxin. New Engl J Med 2000; 342: 664-5.
• 19 Baeuerle PA. The inducible transcription activator NF NFκB. Regulation by distinct protein subunits. Biochem Biophys Acta 1991; 1072: 63-80.
• 20 Wada H, Tamaki S, Tanigawa M, Takagi M, Deguchi A, Mori Y, Katayama N, Yamamoto T, Deguchi K, Shirakawa S. Plasma level of IL-1β in disseminated intravascular coagulation. Thromb Haemost 1991; 65: 364-8.
• 21 Wada H, Ohiwa M, Kaneko T, Tamaki S, Tanigawa M, Takagi M, Mori M, Shirakawa M. Plasma level of tumor necrosis factor in disseminated intravascular coagulation. Am J Hematol 1991; 37: 147-51.
• 22 Wada H, Tanigawa M, Wakita Y, Nakase T, Minamikawa K, Kaneko T, Ohiwa M, Kageyama S, Kobayashi T, Deguchi K, Shirakawa S. Increased plasma level of interleukin-6 in disseminated intravascular coagulation. Blood Coagul Fibrinolysis 1993; 4: 583-90.
• 23 Mackman N. Regulation of tissue factor gene. FASEB J 1995; 9: 883-9.
• 24 Nakasaki T, Wada H, Mori Y, Shimura M, Hiyoyama K, Nishikawa M, Gabazza EC, Miwa H, Kageyama S, Kumeda K, Kato H, Shiku H. Decreased tissue factor and tissue-plasminogen activator antigen in relapsed acute promyelocytic leukemia. Am J Hematol 2000; 64: 145-50.
• 25 Callander NS, Varki N, Rao LV. Immuno-histochemical identification of tissue factor in solid tumors. Cancer 1992; 70: 1194-201.
• 26 Kakkar AK, Lemoine NR, Scully MF, Tebbutt S. Williamson RC. Tissue factor expression correlates with histological grade in human pancreatic cancer. Br J Surg 1995; 82: 1101-4.
• 27 Shugemori C, Wada H, Matsumoto K, Shiku H, Nakamura S, Suzuki H. Tissue factor expression and metastatic potential of colorectal cancer. Thromb Haemost 1998; 80: 894-8.
• 28 Gando S, Kameue T, Nanzaki S, Nakanishi Y. Disseminated intravascular coagulation is a frequent complication of systemic inflammatory response syndrome. Thromb Haemost 1996; 75: 224-8.
• 29 Yamamuro M, Wada H, Kumeda K, Inoue A, Tsuji I, Nishikawa M, Deguchi K, Nakasaki T, Shimura M, Hiyoyama K, Shiku H, Kato H. Changes in plasma tissue factor pathway inhibitor levels during the clinical course of disseminated intravascular coagulation. Blood Coagul Fibrinloysis 1998; 9: 491-7.
• 30 Wada H, Mori Y, Shimura M, Hiyoyama K, Nakasaki T, Ioka M, Nakano M, Nishikawa M, Kumeda K, Nakamura S, Shiku H. Poor outcome in disseminated intravascular coagulation or thrombotic thrombocytopenic purpura patients with severe vascular endothelial cell injuries. Am J Halmatol 1998; 58: 189-94.
• 31 Souter PJ, Thomas S, Hubbard AR, Poole S, Romisch J, Gray E. Antithrombin inhibits lipopolysaccharide-induced tissue factor and interleukin-6 production by mononuclear cells, human umbilical vein endothelial cells, and whole blood. Crit Care Med 2001; 29: 134-9.
• 32 Bernard GR, Vincent JL, Laterre PF, Larosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely W, Fisher CJ. Efficacy and safety of recombinant human protein C for severe sepsis. New Engl J Med 2001; 8: 699-709.