(Circulation. 2000;101:2690.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
High Levels of Platelet Inhibition With Abciximab Despite Heightened Platelet Activation and Aggregation During Thrombolysis for Acute Myocardial Infarction
Results From TIMI (Thrombolysis In Myocardial Infarction) 14
From Brigham and Women’s Hospital (S.A.C., C.P.C., E.M.A., R.P.G., E.B.), Boston, Mass; Maine Medical Center Research Institute (K.A.A.), South Portland, Me; University Hospital Gasthuisberg (F.V.d.W.), Leuven, Belgium; Royal Victoria Hospital (A.A.J.A.), Belfast, UK; Allegheny General Hospital (C.M.G.), Pittsburgh, Pa; Centocor (M.A.M., E.S.B.), Malvern, Pa; Eli Lilly (J.S.), Indianapolis, Ind; and Baylor College of Medicine and The Methodist Hospital (N.S.K.), Houston, Tex.
Correspondence to Neal S. Kleiman, MD, 6565 Fannin, MS F-1090, Houston, TX 7703. E-mail nkleiman{at}bcm.tmc.edu
Background—We evaluated platelet activation and aggregation in patients with acute myocardial infarction (AMI) treated with thrombolytic therapy alone or with reduced-dose thrombolysis and concomitant abciximab.
Methods and Results—The study was performed in 20 control subjects and 51 patients with AMI before and after reperfusion with either alteplase or reteplase or reduced doses of these agents with concomitant abciximab. Platelet activation was assayed by platelet surface expression of P-selectin. Turbidometric platelet aggregation in response to ADP was measured in patients before thrombolytic therapy and 90 minutes and 24 hours after the beginning of thrombolytic therapy. P-selectin expression was greater at baseline in patients than normal control subjects (30.4% versus 9.8%, P<0.0001) but was identical between the 2 groups after stimulation with ADP (64.4% versus 69.3%, P=0.37). However, at 24 hours, basal P-selectin expression declined in patients (P=0.0025 versus baseline), whereas ADP-stimulated P-selectin expression was lower in patients than in control subjects (48% versus 69%, P=0.0004). When combined with reduced doses of either alteplase or reteplase, abciximab achieved 91% and 83% inhibition of 5 and 20 µmol/L ADP–induced platelet aggregation, which decreased to 46% and 40%, respectively, at 24 hours. No appreciable difference in the platelet inhibition profile of abciximab was observed between the 2 thrombolytics.
Conclusions—Platelet activation and aggregation are heightened in the setting of thrombolysis for AMI. Despite this enhanced level of platelet activation, abciximab, combined with a reduced-dose thrombolytic, inhibited platelet aggregation similarly to the level reported in elective settings.
Key Words: myocardial infarction • abciximab • thrombolysis • platelets
This article has been cited by other articles:
 |
|
 |
|
  J. A. Leopold Does Thrombolytic Therapy Facilitate or Foil Primary PCI? N. Engl. J. Med., May 22, 2008; 358(21): 2277 - 2279. [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Giugliano, M. T. Roe, R. A. Harrington, C. M. Gibson, U. Zeymer, F. Van de Werf, K. W. Baran, H.-P. Hobbach, L. H. Woodlief, K. L. Hannan, et al. Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: Results of the integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic urial J. Am. Coll. Cardiol., April 16, 2003; 41(8): 1251 - 1260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Wong, R. P. Giugliano, and E. M. Antman Use of Low-Molecular-Weight Heparins in the Management of Acute Coronary Artery Syndromes and Percutaneous Coronary Intervention JAMA, January 15, 2003; 289(3): 331 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. F. Baker Jr Thrombolytic Therapy Clinical and Applied Thrombosis/Hemostasis, October 1, 2002; 8(4): 291 - 314. [PDF]
|
|
|
|
 |
|
 M. Mirabet, D. Garcia-Dorado, J. Inserte, J. A. Barrabes, R.-M. Lidon, B. Soriano, M. Azevedo, F. Padilla, L. Agullo, M. Ruiz-Meana, et al. Platelets activated by transient coronary occlusion exacerbate ischemia-reperfusion injury in rat hearts Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1134 - H1141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Michelson, M. R. Barnard, L. A. Krueger, C. R. Valeri, and M. I. Furman Circulating Monocyte-Platelet Aggregates Are a More Sensitive Marker of In Vivo Platelet Activation Than Platelet Surface P-Selectin: Studies in Baboons, Human Coronary Intervention, and Human Acute Myocardial Infarction Circulation, September 25, 2001; 104(13): 1533 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Llevadot, R. P. Giugliano, and E. M. Antman Bolus Fibrinolytic Therapy in Acute Myocardial Infarction JAMA, July 25, 2001; 286(4): 442 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Armstrong and D. Collen Fibrinolysis for Acute Myocardial Infarction : Current Status and New Horizons for Pharmacological Reperfusion, Part 2 Circulation, June 19, 2001; 103(24): 2987 - 2992. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lopez-Sendon Coronary reperfusion in the clinical setting: antithrombotic support to thrombolysis in the coronary care unit Eur. Heart J. Suppl., June 1, 2001; 3(suppl_C): C55 - C61. [Abstract] [PDF]
|
|
|
|
 |
|
 E.M Antman, C.M Gibson, J.A de Lemos, R.P Giugliano, C.H McCabe, P Coussement, I Menown, C.A Nienaber, T.C Rehders, M.J Frey, et al. Combination reperfusion therapy with abciximab and reduced dose reteplase: results from TIMI 14 Eur. Heart J., December 1, 2000; 21(23): 1944 - 1953. [Abstract] [PDF]
|
|