title: Thrombin generation and fibrinolytic activities among patients receiving reduced-dose alteplase plus abciximab or undergoing direct angioplasty plus abciximab for acute myocardial infarction.
abstract: The purpose of this study was to determine the impact of these 2 reperfusion strategies (reduced-dose alteplase plus abciximab or direct angioplasty plus abciximab) on fibrinolytic and thrombin generation activities. The effect of reduced-dose alteplase plus abciximab and direct angioplasty plus abciximab on hemostatic factors is unknown. Of 70 patients with acute myocardial infarction of < or = 6 hours, 34 were randomized to reduced-dose alteplase (35 to 50 mg in 1 hour) and 36 to direct angioplasty. A standard bolus and infusion dose of abciximab was administered to all patients. Blood specimens were collected at baseline, and at 1, 4, 12, and 24 hours. The following parameters were assayed: fibrinogen, plasminogen and antiplasmin activities, tissue plasminogen activator antigen, D-dimer, prothrombin fragments F1 + 2, and thrombin/antithrombin III complexes. Among patients treated with reduced-dose alteplase plus abciximab, the fibrinogen level decreased by 28.4% in the first hour (11.7 +/- 3.4 vs 7.8 +/- 2.5 micromol/L, p <0.001). Correspondingly, plasminogen and antiplasmin activities decreased by 43.8% (p <0.001) and 59.1% (p <0.001), respectively. Prothrombin fragments F1 + 2 increased from 2.2 +/- 1.7 to 4.2 +/- 1.6 nmol/L (1 hour) (p <0.001) and thrombin/antithrombin III increased from 16.3 +/- 15.0 to 33.5 +/- 19.9 microg/L (1 hour) (p <0.001). Conversely, in the direct angioplasty group, there was a marginal elevation in fibrinogen level at 1 hour (10.2 +/- 2.4 vs 10.6 +/- 2.0 micromol/L, p = 0.064) despite a significant reduction in plasminogen and an increase in tissue plasminogen activator levels. There was no significant change in prothrombin fragments F1 + 2 and thrombin/antithrombin III levels. Thus, there was considerable fibrinolytic activity with reduced-dose alteplase plus abciximab; thrombin generation was not prevented. Among patients treated with direct angioplasty, there was some endogenous fibrinolytic activity, but there was no significant thrombin generation.
authors.affiliation: Department of Cardiology, National Heart Centre, Singapore. mak_koon_hou@nhc.com.sg
authors.forename: Koon-Hou
authors.initials: KH
authors.lastname: Mak
authors.forename: Lai-Heng
authors.initials: LH
authors.lastname: Lee
authors.forename: Aaron
authors.initials: A
authors.lastname: Wong
authors.forename: Charles
authors.initials: C
authors.lastname: Chan
authors.forename: Tian-Hai
authors.initials: TH
authors.lastname: Koh
authors.forename: Kean-Wah
authors.initials: KW
authors.lastname: Lau
authors.forename: Yean-Leng
authors.initials: YL
authors.lastname: Lim
mesh_terms: D000077284:Abciximab; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D005260:Female; D005342:Fibrinolysis; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000628:therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D013917:Thrombin / Q000096:biosynthesis*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D000077284:Abciximab