In addition, regarding the prevention of the postphlebitic syndrome, the results of the few studies presently available are contradictory. Thus, heparin has remained the mainstay of treatment for DVT, mainly because of fear of an unfavorable ratio of efficacy to bleeding side effects with thrombolytic agents.
Preliminary clinical experience with rt-PA in patients with DVT has shown that even this fibrin-specific plasminogen activator causes hemorrhagic complications. Verhaeghe and coworkers infused rt-PA over 8 h on days 1 and 2 at the total dose of 150 or 100 mg. Major hemorrhagic complications occurred in 8 of25 (32%) patients who received the thrombolytic agent. In the study performed by Turpie, hemorrhagic complications were observed in 5 of 43 patients with DVT who received 0.5 mg/kg of rt-PA infused over 4 or 8 h.
Recently, Goldhaber and coworkers compared the efficacy and safety of rt-PA with rt-PA plus heparin or heparin alone in the treatment of DVT of the leg. Patients assigned to rt-PA groups received 0.05 mg/ kg/h for 24 h, with a maximum dose of 150 mg. Minor bleeding was observed in 9 of 36 patients treated with rt-PA alone and in 2 of 17 patients treated with rt-PA plus heparin. One nonfatal episode of intracranial bleeding occurred in the rt-PA group. No hemorrhagic complications were seen in the group receiving heparin alone. In all of these studies, rt-PA induced a significant increase in clot lysis in comparison with heparin. Thus, alternative therapeutic regimens of rt-PA should be investigated in order to improve its safety, and possibly efficacy, in patients with DVT. Increased safety of therapeutic thrombolysis is particularly desirable in clinical disorders with low mortality, such as DVT.