Rebound increase of PAI-1 following local intra-arterial rt-PA infusion, a possible cause of reocclusion.
We studied systemic changes in the plasminogen activating system induced by local intra-arterial infusion of recombinant t-PA (rt-PA) in ten patients with arterial occlusion. The arterial infusion of rt-PA resulted in an immediate increase of t-PA activity and antigen in venous plasma. Concomitantly the plasma was depleted of PAI-1 activity with a moderate decrease of PAI-1 antigen, presumably due to immediate complexing of rt-PA by PAI-1 and gradual elimination of the rt-PA/PAI-1 complex from the circulation. Activation of plasminogen in the circulation was reflected by the occurrence of fibrinogen/fibrin degradation products. This rapid systemic activation of the fibrinolytic system at local intra-arterial administration of rt-PA might be due to the opening of small collaterals or backward flow through open arteries, allowing rt-PA to enter the general circulation. The disappearance of detectable PAI-1 activity during rt-PA infusion was followed by a rebound effect with a significant increase of PAI-1 antigen. As this increase may have contributed to the reocclusion which occurred in four patients, it might be advisable to replace heparin by rt-PA at a lower dosage in the immediate phase following rt-PA infusion.
Astedt
B
B
Department of Gynaecology and Obstetrics, University of Lund, University Hospital, Sweden.
Casslén
B
B
Lecander
I
I
Nilsson
L
L
Norgren
L
L
D000368:Aged; D000369:Aged, 80 and over; D001157:Arterial Occlusive Diseases / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012008:Recurrence; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator