Monitoring heparin treatment with the activated partial thromboplastin time (1972)


Treatment of VTE with heparin

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To seek a relation between the aPTT and recurrent VTE or bleeding during heparin treatment

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Trial design

Prospective, open study
Active treatment: All patients (n=234) received an initial i.v. bolus of 5000 IU heparin, followed by a maintenance dose of 24,000 IU per 24 h given by continuous i.v. infusion and adjusted to keep the aPTT between 1.5 and 2.5 times the control level of 40 s all times. All patients were treated for 7–10 days

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Primary endpoints in patients treated for venous embolism: recurrent symptomatic VTE and bleeding during heparin treatment
Primary endpoints in patients treated for other reasons: bleeding events

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Trial participants

A total of 234 patients entered the study. 162 of these patients (mean age 54 years) were treated for venous thrombolic disease and the remaining 72 patients (mean age 57 years) for myocardial infarction or arterial thromboembolism, or to prevent venous thrombosis. 67 patients were treated after surgery

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Efficacy outcome: Only 5 of 162 patients (3%) developed a recurrence of VTE. These patients received a mean dose of 34.100 IU heparin per 24 h before recurrence and had a mean aPTT of 49 s. This amount compared with a mean dose of 29,900 IU and a mean aPTT of 66 s in the 157 patients without recurrence (p<0.005 for aPTT). After recurrence, patients were treated with 47,300 IU heparin per 24 h (p<0.01 vs. dose in patients without recurrence) and reached a mean aPTT of 67 s – a value similar to that of patients without recurrence. Further analysis showed that the time spent with an aPTT <50 s provided the best discrimination between patients with and those without recurrence
Safety outcome: Bleeding occurred in 19 of all 234 heparin treated patients: in 9 of 67 postoperative patients (13.4%) and in 10 of 167 medical patients (6.0%). Their mean heparin dose and aPTT were similar to those of patients without bleeding complications

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Efficacy: The results of the study suggest that patients with VTE should be given enough heparin to prolong the aPTT >1.5 times the control level, irrespective of the amount of heparin required to obtain that result
Safety: Even with an aPTT of 1.5–2.5, bleeding complications can not be avoided, especially in postoperative patients

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Basu D, Gallus A, Hirsh J, Cade J. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time. N Engl J Med 1972;287:324-327

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Corresponding author

Dilip Basu, MD, St. Joseph’s Hospital, Hamilton, Ontario, Canada

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