RELATION BETWEEN THE TIME TO ACHIEVE THE LOWER LIMIT OF THE APTT THERAPEUTIC RANGE AND RECURRENT VENOUS THROMBOEMBOLISM DURING HEPARIN TREATMENT FOR DEEP-VEIN THROMBOSIS

Background: Randomized-trials have demonstrated the importance of achi eving adequate heparinization early in the course of therapy. Recently , some authors reported a pooled analysis of selected studies in the l iterature that suggested that there is no convincing evidence that the risk of recurrent venous thromboembolism is critically dependent on a chieving a therapeutic activated partial thromboplastin time result at 24 to 48 hours. Methods: We provide the analyses of patient groups en tered into our series of 3 consecutive double-blind randomized trials evaluating initial heparin therapy for proximal deep venous thrombosis . Results: logistic regression analysis of the patient groups receivin g the less intense initial intravenous heparin dose of 30000 U/24 h de monstrated that subtherapy for 24 hours predicted the onset of venous thromboembolic events. Failure to achieve a therapeutic activated part ial thromboplastin time by 24 hours was associated with a 23.3% freque ncy of venous thromboembolism vs 4% to 6% for those whose activated pa rtial thromboplastin time exceeded the therapeutic threshold by 24 hou rs (P=.02). Time-to-event analysis shows the increased frequency of re current venous thromboembolic events during the period of study in pat ients who were subtherapeutic for 24 hours compared with those who wer e therapeutic (P=.001). Conclusions: Our findings reaffirm the clinica l importance of rapidly achieving therapeutic levels of heparin. Patie nts who failed to achieve the therapeutic threshold by 24 hours were a t an increased risk of subsequent recurrent venous thromboembolism The se findings are independently supported by the results of a randomized trial comparing different intensities of initial heparin treatment by continuous infusion.