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Recurrent Venous Thrombosis and Heparin Therapy
An Evaluation of the Importance of Early Activated Partial Thromboplastin Times
Sonia S. Anand, MD, MSc;
Shannon Bates, MD, CM;
Jeffrey S. Ginsberg, MD;
Mark Levine, MD;
Harry Buller, MD;
Martin Prins, MD;
Susan Haley, BSc;
Clive Kearon, MB;
Jack Hirsh, MD;
Michael Gent, DSc
Arch Intern Med. 1999;159:2029-2032.
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 (IV) unfractionated heparin (UFH).
Patients and Methods We studied 961 patients with acute VTE who received IV UFH in 3 randomized trials that compared the use of IV UFH (loading dose: 5000 U IV; 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 IV 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.
From the Departments of Medicine, McMaster University, Hamilton, Ontario (Drs Anand, Bates, Ginsberg, Levine, Kearon, Hirsh, and Gent and Ms Haley), and the Center for Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands (Drs Buller and Prins).
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