Recurrent Venous Thrombosis and Heparin Therapy: An Evaluation of the Importance of Early Activated Partial Thromboplastin Times

BACKGROUND: The presence of an association between early subtherapeutic activated partial thromboplastin times (aPTTs) and recurrent venous thromboembolism (VTE) remains controversial. OBJECTIVE: To determine the relation between early subtherapeutic aPTTs and recurrent VTE in patients who were treated with intravenous (i.v.) unfractionated heparin (UFH). PATIENTS AND METHODS: We studied 961 patients with acute VTE who received i.v. UFH in 3 randomized trials that compared the use of i.v. UFH (loading dose: 5000 U i.v.; initial infusion, 1250-1280 U/h) with that of subcutaneous low-molecular-weight heparin. According to aPTT criteria, patients were classified as being in a subtherapeutic or a therapeutic state during the first 24 and 48 hours of treatment. All episodes of possible recurrent VTE were adjudicated by an independent committee that was unaware of the aPTTs. RESULTS: At 24 hours, in 886 patients who were eligible for the analysis, the rate of recurrent VTE in the subtherapeutic group was 6.7% (11/163) compared with 5.3% (38/723) in the therapeutic group. The odds ratio for recurrence in patients in the subtherapeutic vs the therapeutic group at 24 hours was 1.30 (95% confidence interval: 0.64-2.63; P = .46). At 48 hours, in 917 patients who were eligible for the analysis, the rate of recurrent VTE in the subtherapeutic group was 7.8% (5/64) compared with 5.7% (49/853) in the therapeutic group. The odds ratio for recurrence in patients in the subtherapeutic vs the therapeutic group at 48 hours was 1.32 (95% confidence interval: 0.51-3.44; P = .56). CONCLUSION: In patients with acute VTE who receive an i.v. bolus of 5000 U, followed by a starting dose of at least 1250 U/h of UFH, a subtherapeutic aPTT response during the first 48 hours of treatment is not associated with a large increase in the risk of recurrent VTE.