Activation of blood coagulation and fibrinolysis has previously been detected in stroke patients. It is unknown, however, what factors contribute to the acceleration of coagulation reactions, especially in cases where no obvious predisposing factors exist. We therefore postulated and tested the hypothesis that in such patients monocytes may trigger the pathway leading to thrombosis by expressing tissue factor (TF). TF antigen was determined in 48 patients and 40 controls by flow cytometry using an indirect immunofluorescent technique. TF antigen expression was significantly increased on monocytes in young stroke patients in both the acute (p < 0.01) and chronic (p < 0.05) phases of the disease. The TF antigen also possessed functional activity, quantitated by a one-stage clotting assay. TF expression on monocytes was not associated with an elevation in C-reactive protein values. In both acute and chronic phases, blood coagulation activation markers, e.g. the thrombin-antithrombin complex and F1+2 fragments, were significantly elevated. However, in the acute phase D-dimer levels were similar to those in controls and were only elevated in the chronic phase of the disease (p < 0.05). In conclusion, in cerebral ischemia TF expression on monocytes suggests enhanced activation of blood coagulation and subsequent fibrinolysis.

Keywords:
Cerebrovascular disorders, Blood coagulation, Monocyte, Tissue factor, Stroke
1.
Takano K, Yamaguchi T, Kato H, Omaz T: Activation of coagulation in acute cardioembolic stroke. Stroke 1991;22:12–16.
2.
Tohgi H, Takahashi H, Chiba K, Tamara K: Coagulation – Fibrinolysis system in poststroke patients receiving antiplatelet medication. Stroke 1993;24:801–804.
3.
Feinberg WM, Bruck DC, Ring ME, Corrigan JJ: Hemostatic markers in acute stroke. Stroke 1989;20:592–597.
4.
Fon EA, Mackey A, Coté R, Wolfson C, Mc Ilraith DM, Leclerc J, Bourque F: Hemostatic markers in acute transient ischemic stroke. Stroke 1994;25:282–286.
5.
Mariner HR, Raugel-Guerra RA, Marfil LJ: Ischemic stroke due to deficiency of coagulation inhibitors. Report of 10 young adults. Stroke 1993;24:19–25.
6.
Halbmayer WM, Haustiofer A, Schou R, Fischer M: The prevalence of poor anticoagulant response to activated protein C (APC resistance) among patients suffering from stroke or venous thrombosis and among healthy subjects. Blood Coagul Fibrinolysis 1994;5:51–57.
7.
Barinagarrementeria F, Cantu-Brito C, De La Pena, Izaquirre R: Prothrombotic states in young people with idiopathic stroke. A prospective study. Stroke 1994;25:287–290.
8.
Brown DC, Livingston JH, Minns RA, Eden OB: Protein C and S deficiency causing childhood stroke. Scott Med J 1993;38:114–115.
9.
Mitsias P, Levine SR: Large cerebral vessel occlusive disease in systemic lupus erythematosus. Neurology 1994;44:385–393.
10.
Ferro D, Quintarelli C, Rasura M, Antonini G, Violi F: Lupus anticoagulant and the fibrinolytic system in young patients with stroke. Stroke 1993;24:368–370.
11.
Conkling PR, Greenberg CS, Weinberg JB: Tumor necrosis factor induces tissue-factor like activity in human leukemia cell line U 937 and peripheral blood monocytes. Blood 1988;72:128–133.
12.
Niemetz J, Fami K: Thrombogenic activity of leukocytes. Blood 1973;42:47–59.
13.
Belch JJF: The role of the white blood cell in arterial disease. Blood Coagul Fibrinolysis 1990;1:183–192.
14.
Levy GA, Edgington TS: Lymphocyte cooperation is required for amplification of macrophage procoagulant activity. J Exp Med 1980;151:1232–1244.
15.
Kappelmayer J, Bernabei A, Edmunds LH, Edgington TS, Colman RW: Tissue factor is expressed on monocytes during simulated extracorporeal circulation. Circ Res 1993;72:1075–1081.
16.
Niemetz J: Coagulant activity of monocytes. J Clin Invest 1972;51:307–313.
17.
Muhlfelder TW, Niemetz J, Kreutzer D, Beebe D, Ward PA, Rosenfeld SI: C5 chemotactic fragment induces monocyte production of tissue factor activity. J Clin Invest 1979;63:147–150.
18.
Schwartz BS, Edgington TS: Immune complex induced human monocyte procoagulant activity. J Exp Med 1981;154:892–906.
19.
Levy GA, Schwartz BS, Curtiss LK, Edgington TS: Plasma lipoprotein induction and suppression of the generation of cellular procoagulant activity in vitro. J Clin Invest 1981;67:1614–1622.
20.
Cermak J, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM: C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993;82:513–520.
21.
Peltola HO: C reactive protein for rapid monitoring of infections of the central nervous system. Lancet 1982;i:980–982.
22.
Beamer NB, Coull BM, Clark WH, Hazel JS, Silberger JR: Interleukin 6 and interleukin 1 receptor antagonist in acute stroke. Ann Neurol 1995;37:800–805.
23.
Haan J, Kluft C, Leebeek FW, deBart AC, Buruma OJ, Roos RA: Hereditary cerebral haemorrhage with amyloidosis-Dutch type: A study of fibrinolysis. Thromb Haemost 1992;67:16–18.
24.
Sandset PM, Anderson TR: Coagulation inhibitor levels in pneumonia and stroke: Changes due to consumption and acute phase reaction. J Intern Med 1989;225:311–316.
25.
Amirkhosravi A, Alexander M, May K, Francis DA, Warnes G, Biggerstaff J, Francis JL: The importance of platelets in the expression of monocyte tissue factor antigen measured by a new whole blood flow cytometric assay. Thromb Haemost 1996;75:87–95.
26.
Edgington TS, Colman RW, Kappelmayer J, Edmunds LH, Bernabei A: Method of inhibiting blood coagulation in extracorporeal circulation by inhibiting human tissue factor. United States Patent 5,437,864, Aug 1, 1995.
27.
Thomas WS, Mori E, Copeland Br, Yu JQ, Morrissey JH, del Zoppo G: Tissue factor contributes to microvascular defects after focal cerebral ischemia. Stroke 1993;24:847–853.
1998
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