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

• Published in: Blood coagulation & fibrinolysis Vol. 11; no. 6; p. 529
• Main Authors: Grünewald, M, Griesshammer, M, Ellbrück, D, Kuhn, S, Seifried, E, Osterhues, H
• Format: Journal Article
• Language: English
• Published: England 01.09.2000
• Subjects: Adult; Aged; Antifibrinolytic Agents - administration & dosage; Antifibrinolytic Agents - blood; Antifibrinolytic Agents - pharmacokinetics; Fibrinolytic Agents - administration & dosage; Fibrinolytic Agents - pharmacokinetics; Fibrinolytic Agents - standards; Hemorrhage - chemically induced; Hemostasis - physiology; Humans; Infusions, Intravenous - standards; Leg - blood supply; Leg - pathology; Male; Middle Aged; Plasminogen Activators - administration & dosage; Plasminogen Activators - blood; Plasminogen Activators - pharmacokinetics; Reperfusion - standards; Tissue Plasminogen Activator - administration & dosage; Tissue Plasminogen Activator - blood; Tissue Plasminogen Activator - pharmacokinetics; Venous Thrombosis - complications; Venous Thrombosis - therapy
• ISSN: 0957-5235
• DOI: 10.1097/00001721-200009000-00004

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 it 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 tightly bandaged; alteplase infusions were repeated every 24 h, the number of therapy cycles (TC) was seven, and full-dose heparin was given. For coagulation analyses, 'loco-regional' blood samples were taken from a vein of the affected leg and 'systemic' samples were taken from an antecubital vein. After 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 FgDPs and d-dimers, were elevated significantly loco-regionally over systemic values, and a complete breakdown of plasmin-inhibitor activity occurred with only a slight systemic reduction; no other differences were found. During successive TC, differences in rtPA-activity and -antigen levels decreased, and no significant differences were found for all other parameters. Thus, a local fibrinolytic effect was demonstrable during loco-regional thrombolysis for DVT; the magnitude of this effect diminished during successive TC, giving rise to the hypothesis that the fibrinolytic efficacy may be decreased due to growing, antifibrinolytic activity. The preserved, loco-regional plasmin-inhibitor activities during the later TC, in contrast to the complete breakdown during the first TC, suggest that part of the enhanced antifibrinolytic 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 achieved.