Anticoagulant effects of low-molecular-weight heparin following thrombolytic therapy in acute myocardial infarction: a dose-finding study.
The aim of the present study was to gain clinical experience with different dose levels of dalteparin, a low-molecular-weight heparin, following thrombolytic therapy in acute myocardial infarction. Compared to heparin, dalteparin has a longer half-life and a greater and highly predictable bioavailability, which would suggest dalteparin to be a convenient alternative. Twenty patients with ECG signs of acute transmural myocardial ischemia received streptokinase (1.5 million IU for 60 min) and were allocated to a control group or to open treatment with 50, 75 or 100 IU of dalteparin/kg b.w. s.c. b.i.d., starting 4 h later, for 6 days. Each group consisted of 5 patients. Except for the control group, aspirin was withheld during dalteparin treatment. Anti-factor-Xa (anti-FXa) values increased dose-dependently during the first 24 h and were maintained throughout the study period. On day 6, anti-FXa levels after 100 IU/kg b.w. were 0.79 (0.59-1.00) IU/ml (median, min.-max.) 4 h after administration of dalteparin, and 0.51 (0.34-0.82) IU/ml before the subsequent dose of dalteparin. In conclusion, our results indicate that a dalteparin dose slightly higher than 100 IU/kg b.w. is required in order to obtain the presumed therapeutic range of anti-FXa (0.6-1.0 IU/ml).
Division of Internal Medicine, Karolinska Institutet, Danderyd Hospital, Sweden.
L E
LE
Strandberg
T
T
Kahan
P
P
Lundin
J
J
Svensson
L
L
Erhardt
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D000990:Antithrombin III / Q000378:metabolism; D017985:Dalteparin / Q000009:adverse effects / Q000627:therapeutic use*; D003710:Demography; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010314:Partial Thromboplastin Time; D012044:Regression Analysis; D015912:Thrombolytic Therapy
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D000990:Antithrombin III; D005340:Fibrinogen; D017985:Dalteparin