Systemic Thrombin Generation and Activity Resistant to Low Molecular Weight Heparin Administered Prior to Streptokinase in Patients with Acute Myocardial Infarction

Abstract

SummaryOne hundred patients were included in a randomized open trial to assess the systemic factor Xa (FXa) and thrombin inhibitory effect as well as the safety profile of low molecular weight heparin (LMWH) given subcutaneously in conjunction with streptokinase (SK) in patients with acute myocardial infarction (MI). The treatment was initiated prior to SK, followed by repeated injections every 12 h for 7 days, using a dose of 150 anti-Xa units per kg body weight. The control group received unfractionated heparin (UFH) 12,500 IU subcutaneously every 12 h for 7 days, initiated 4 h after start of SK infusion. All patients received acetylsalicylic acid (ASA) initiated prior to SK.Serial blood samples were collected prior to and during the first 24 h after initiation of SK infusion for determination of prothrombin fragment 1+2 (Fl+2), thrombin-antithrombin III (TAT) complexes, fibrinopeptide A (FPA) and cardiac enzymes. Bleeding complications and adverse events were carefully accounted for.Infarct characteristics, as judged by creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT), were similar in both groups of patients.A comparable transient increase in Fl+2, TAT and FPA was noted irrespective of heparin regimen. Increased anti-Xa activity in patients given LMWH prior to thrombolytic treatment had no impact on indices of systemic thrombin activation.The incidence of major bleedings was significantly higher in patients receiving LMWH as compared to patients receiving UFH. However, the occurrence of bleedings was modified after reduction of the initial LMWH dose to 100 anti-Xa units per kg body weight.In conclusion, systemic FXa- and thrombin activity following SK-infusion in patients with acute MI was uninfluenced by conjunctive LMWH treatment.

Unfractionated and Low-Molecular-Weight Heparin as Adjuncts to Thrombolysis in Aspirin-Treated Patients With ST-Elevation Acute Myocardial Infarction

“…After review of abstracts, an additional 16 studies were excluded. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] After review of the full article, an additional 8 studies were excluded because they were not properly randomized (nϭ3) [33][34][35] ; because at least 1 randomized treatment group did not receive aspirin (nϭ3) 36 -38 ; or because they were preliminary reports or the results of a substudy with the main results having been reported elsewhere (nϭ2). 39,40 Clinical outcome data could not be obtained for 1 additional study, 41 leaving 14 randomized trials, involving a combined total of 25 280 patients, for inclusion in the meta-analysis (Tables 1 to 3).…”

Comparison of Enoxaparin and Unfractionated Heparin on Thrombin Generation in Acute Coronary Syndromes without ST-Segment Elevation

“…Ernofsson and co-workers (16) demonstrated that s. c. dalteparin was able to reduce both thrombin activation and generation in unstable angina. Nilsen (17) obtained similar results in patients with myocardial infarction treated with streptokinase, whereas Grosset et al (18) observed a similar TAT inhibition and a more pronounced F1+2 inhibition with enoxaparin, as compared to standard heparin, in patients with venous thromboembolism. Our data show that in patients with unstable angina or NQAMI, enoxaparin, at the dosages reported above, produces a fifty-percent reduction of thrombin activity and generation within 3 h. This effect was similar to that obtained with anticoagulant doses of UFH and persisted in the following 3 days of observation.…”

Enzyme electrophoresis method in analysis of active components of haemostasis system

“…Increased levels of thrombin-antithrombin III complex, fibrinopeptide A, prothrombin fragment F1 + 2 and D-dimer are detectable in patients affected by thrombosis. [26][27][28][29][30]. The level of t-PA antigen is increased but associated with decreased t-PA activity [31][32][33].…”