Fibrinogen breakdown, long-lasting systemic fibrinolysis, and procoagulant activation during alteplase double-bolus regimen in acute myocardial infarction.
Recent clinical studies comparing accelerated versus bolus administration of alteplase tissue plasminogen activator (t-PA) suggest similar thrombolytic efficacy, but reveal higher bleeding complications among older patients during the double-bolus regimen. The objective of the present study was to characterize the hemostatic profile of t-PA administered as double-bolus doses of 50 mg, at intervals of 30 minutes. Among 50 patients with acute myocardial infarction treated by double-bolus t-PA thrombolysis, coagulation and fibrinolysis parameters, as well as t-PA levels, were monitored. Monitored t-PA levels peaked at 5 and 35 minutes and were detectable within the therapeutic range even after 90 minutes. Marked systemic fibrinolytic activation was indicated by 75% depletion of both plasminogen and fibrinogen, as well as by 19-fold and 300-fold increases of fibrin degradation and fibrinogen degradation products. Plasminogen-activator inhibitor activity was completely suppressed. Pronounced procoagulant activation was reflected by a 3.4-fold increase of both factor XIIa and prothrombin fragment 1+2, and by a threefold increase of thrombin-antithrombin complex. Independent of t-PA weight dosage, fibrinolytic activation was more pronounced among older patients (> or = 63 years). We conclude that t-PA after bolus administration has a long half-life. Double-bolus regimen leads to a long-lasting systemic fibrinolytic state, which is even more remarkable among older patients--a fact that may explain the higher bleeding complications reported for this age group.
Stangl
K
K
Medizinische Klinik und Poliklinik I, Universitätsklinik Charité, Humboldt Universität zu Berlin, Germany.
Laule
M
M
Tenckhoff
B
B
Stangl
V
V
Gliech
V
V
Dübel
P
P
Grohmann
A
A
Melzer
C
C
Langel
J
J
Wernecke
K D
KD
Baumann
G
G
Ziemer
S
S
D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000187:drug effects; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010960:Plasminogen Activators / Q000008:administration & dosage* / Q000627:therapeutic use; D011446:Prospective Studies; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000627:therapeutic use
D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; D005340:Fibrinogen; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator