Activation of the complement system by recombinant tissue plasminogen activator

Recent trials have shown that recombinant tissue plasminogen activator (rt-PA) is an effective thrombolytic agent in patients with acute myocardial infarction. Because rt-PA converts plasminogen to plasmin, which is known to activate complement in vitro, we tested the hypothesis that rt-PA can induce in vivo activation of complement. Studies were performed in 12 patients with acute myocardial infarction. Six control patients had patent coronary arteries and did not receive rt-PA; these patients had normal values of the components of the complement system C4a (409 +/- 111 ng/ml) and C5a (8.8 +/- 1.8 ng/ml) with a slight elevation of C3a (204 +/- 6.6 ng/ml) in samples collected before coronary arteriography (253 +/- 25 minutes after onset of pain). After coronary arteriography, there was a slight decrease in the values of C4a (224 +/- 37 ng/ml), C5a (7.3 +/- 1.3 ng/ml) and C3a (164 +/- 35 ng/ml). The remaining six patients had complete coronary occlusion and received rt-PA (80 to 150 mg intravenously). In this treated group, before coronary arteriography the values of C4a (406 +/- 51.6 ng/ml) and C5a (8.1 +/- 1.9 ng/ml) were normal, and those of C3a were slightly elevated (250 +/- 76 ng/ml). All complement values obtained before rt-PA were similar to those in the untreated group. However, after administration of rt-PA (but before any angiographically detectable reperfusion), there was a striking increase in C4a (2,265 +/- 480 ng/ml; p less than 0.01), C3a (600 +/- 89 ng/ml; p less than 0.05) and C5a (30.0 +/- 4.5 ng/ml; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				L. R. La Bonte, V. I. Pavlov, Y. S. Tan, K. Takahashi, M. Takahashi, N. K. Banda, C. Zou, T. Fujita, and G. L. Stahl Mannose-Binding Lectin-Associated Serine Protease-1 Is a Significant Contributor to Coagulation in a Murine Model of Occlusive Thrombosis J. Immunol., January 15, 2012; 188(2): 885 - 891. [Abstract] [Full Text] [PDF]

				C.-H. Tan, S.-C. Tang, R.-J. Lin, and J.-S. Jeng Orolingual angio-oedema after alteplase therapy in a stroke patient concurrently using angiotensin II receptor blocker J. Neurol. Neurosurg. Psychiatry, October 1, 2010; 81(10): 1079 - 1079. [Full Text] [PDF]

				T. V. Arumugam, S.-C. Tang, J. D. Lathia, A. Cheng, M. R. Mughal, S. Chigurupati, T. Magnus, S. L. Chan, D.-G. Jo, X. Ouyang, et al. Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death PNAS, August 28, 2007; 104(35): 14104 - 14109. [Abstract] [Full Text] [PDF]

				K. Fattouch, G. Bianco, G. Speziale, R. Sampognaro, C. Lavalle, F. Guccione, P. Dioguardi, and G. Ruvolo Beneficial effects of C1 esterase inhibitor in ST-elevation myocardial infarction in patients who underwent surgical reperfusion: a randomised double-blind study, Eur J Cardiothorac Surg, August 1, 2007; 32(2): 326 - 332. [Abstract] [Full Text] [PDF]

				C. L. Grines, D. R. Westerhausen Jr, L. L. Grines, J. T. Hanlon, T. L. Logemann, M. Niemela, W. D. Weaver, M. Graham, J. Boura, W. W. O'Neill, et al. A randomized trial of transfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction: The air primary angioplasty in myocardial infarction study J. Am. Coll. Cardiol., June 5, 2002; 39(11): 1713 - 1719. [Abstract] [Full Text] [PDF]

				J. Rudolf, M. Grond, S. Schmulling, M. Neveling, and W.-D. Heiss Orolingual angioneurotic edema following therapy of acute ischemic stroke with alteplase Neurology, August 22, 2000; 55(4): 599 - 600. [Full Text] [PDF]

				M. D. Hill, P. A. Barber, J. Takahashi, A. M. Demchuk, T. E. Feasby, and A. M. Buchan Anaphylactoid reactions and angioedema during alteplase treatment of acute ischemic stroke Can. Med. Assoc. J., May 2, 2000; 162(9): 1281 - 1284. [Abstract] [Full Text] [PDF]

				Y. J. Gu, M. A. Mariani, P. W. Boonstra, J. G. Grandjean, and W. v. Oeveren Complement Activation in Coronary Artery Bypass Grafting Patients Without Cardiopulmonary Bypass: The Role of Tissue Injury by Surgical Incision Chest, October 1, 1999; 116(4): 892 - 898. [Abstract] [Full Text] [PDF]

				R. L. Zhang, Z. G. Zhang, M. Chopp, and J. A. Zivin Thrombolysis With Tissue Plasminogen Activator Alters Adhesion Molecule Expression in the Ischemic Rat Brain Editorial Comment Stroke, March 1, 1999; 30(3): 624 - 629. [Abstract] [Full Text] [PDF]

				N. Aoki and H. Tomoda Plasma Soluble P-Selectin in Acute Myocardial Infarction: Effects of Coronary Recanalization Therapy Angiology, September 1, 1998; 49(9): 807 - 813. [Abstract] [PDF]

				V. J. Christiansen, P. J. Sims, and K. K. Hamilton Complement C5b-9 Increases Plasminogen Binding and Activation on Human Endothelial Cells Arterioscler Thromb Vasc Biol, January 1, 1997; 17(1): 164 - 171. [Abstract] [Full Text]

				P. R. Hansen Role of Neutrophils in Myocardial Ischemia and Reperfusion Circulation, March 15, 1995; 91(6): 1872 - 1885. [Abstract] [Full Text]