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 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.
Grünewald
M
M
Department of Medicine, Haemostaseology, University of Ulm, Germany. martin.gruenewald@medizin.uni-ulm.de
Griesshammer
M
M
Ellbrück
D
D
Kuhn
S
S
Seifried
E
E
Osterhues
H
H
D000328:Adult; D000368:Aged; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000592:standards; D006470:Hemorrhage / Q000139:chemically induced; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous / Q000592:standards; D007866:Leg / Q000098:blood supply / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D015424:Reperfusion / Q000592:standards; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D020246:Venous Thrombosis / Q000150:complications / Q000628:therapy*
D000933:Antifibrinolytic Agents; D005343:Fibrinolytic Agents; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator