Use of a standardized heparin nomogram to achieve therapeutic anticoagulation after thrombolytic therapy in myocardial infarction. TIMI 4 investigators. Thrombolysis in Myocardial Infarction

Arch Intern Med. 1994 Jul 11;154(13):1492-6.


Background: The recently completed Thrombolysis in Myocardial Infarction (TIMI) 4 Study compared three thrombolytic treatment regimens for acute myocardial infarction. The treatment arms included front-loaded recombinant tissue plasminogen activator (rtPA), anistreplase (APSAC), or both, in conjunction with an intravenous bolus of 5000 U of heparin, followed by 1000 U/h. To facilitate anticoagulation, a heparin nomogram was developed to maintain the therapeutic activated partial thromboplastin time at 1 1/2 to 2 times the control value.

Methods: A poll revealed that nine centers made use of the recommended heparin nomogram and six did not, adjusting the heparin dosage according to local practice. Anticoagulation parameters, major hemorrhagic events, and the frequency of heparin interruption were compared between centers that used and did not use the nomogram.

Results: Subtherapeutic activated partial thromboplastin time values were noted in 4%, 14%, 29%, 46%, 37%, and 34% of patients 8, 12, 24, 48, 72, and 96 hours, respectively, after heparin treatment was begun. Patients with subtherapeutic values at 24 hours were younger (mean +/- SD, 55.2 +/- 10.6 vs 59.6 +/- 10.6 years, P = .02) and weighed more (86.4 +/- 13.5 vs 78.9 +/- 15.7 kg, P = .007) than patients with therapeutic values. Centers that used the nomogram had significantly fewer subtherapeutic values at 48 and 96 hours. In addition, heparin therapy was interrupted less frequently at centers that used the nomogram (38.1% vs 68.7%, P < .001). Major spontaneous hemorrhage, reinfarction, and reocclusion rates were low and were about the same in the two groups.

Conclusions: The use of a heparin nomogram provided improved anticoagulation in patients treated with thrombolytic therapy for myocardial infarction. Weight- and age-adjusted heparin dosing may provide further improvement in anticoagulation with heparin therapy. Our findings support the need for frequent monitoring of the activated partial thromboplastin time and for a standardized approach to adjusting the heparin dosage.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Heparin / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Partial Thromboplastin Time
  • Thrombolytic Therapy*


  • Heparin