Loco-regional thrombolysis for deep vein thrombosis: fact or fiction? A study of hemostatic parameters

Loco-regional thrombolysis for deep-vein thrombosis (DVT) has been claimed to be equally effective and safe compared with systemic thrombolysis. It is not known whether a loco-regional thrombolytic effect exists and of what i t might consist. To investigate this issue, we studied eight patients with DVT undergoing loco-regional thrombolysis with 20 mg alteplase infused over 4 h in a dorsal foot-vein of the affected leg, while the leg was kept tigh tly bandaged; alteplase infusions were repeated every 24 h, the number of t herapy cycles (TC) was seven, and full-dose heparin was given. For coagulat ion analyses, 'loco-regional' blood samples were taken from a vein of the a ffected leg and 'systemic' samples were taken from an antecubital vein. Aft er a median number of six TC, good partial reperfusion was achieved in 4/8 patients, moderate partial reperfusion in 2/8, major bleedings occurred in 2/8, and minor bleedings in 1/8 patients. During the first TC, recombinant tissue-type plasminogen activator (rtPA) activity and antigen, as well as F gDPs and d-dimers, were elevated significantly loco-regionally over systemi c values, and a complete breakdown of plasmin-inhibitor activity occurred w ith only a slight systemic reduction; no other differences were found. Duri ng successive TC, differences in rtPA-activity and -antigen levels decrease d, and no significant differences were found for all other parameters. Thus , a local fibrinolytic effect was demonstrable during loco-regional thrombo lysis for DVT; the magnitude of this effect diminished during successive TC , giving rise to the hypothesis that the fibrinolytic efficacy may be decre ased due to growing, antifibrinolytic activity. The preserved, loco-regiona l plasmin-inhibitor activities during the later TC, in contrast to the comp lete breakdown during the first TC, suggest that part of the enhanced antif ibrinolytic activity is due to loco-regionally increased plasmin-inhibitor activity. The ultimate goal of loco-regional thrombolysis, the induction of local fibrinolysis without systemic effects, has not, however, been achiev ed. Blood Coagul Fibrinolysis 11:529-536 (C) 2000 Lippincott Williams & Wil kins.