Possible mechanism of vascular reocclusion after initially successful thrombolysis with recombinant tissue-type plasminogen activator.
We studied the effects of urokinase (UK), pro-urokinase (pro-UK), and recombinant tissue-type plasminogen activator (rt-PA) on platelet aggregation and the production of thromboxane A2 (TXA2) in vitro. Both UK and pro-UK inhibited the platelet aggregation induced by adenosine 5'-diphosphate (ADP), collagen, or thrombin in a concentration-dependent manner. In contrast, although a low dose of rt-PA (5 to 10 x 10(4) U/ml) blunted platelet aggregability, a high dose (40 to 60 x 10(4) U/ml) led to platelet hyperaggregation. UK and pro-UK markedly inhibited TXA2 synthesis during ADP-induced platelet aggregation. Despite the significant reduction of TXA2 synthesis by 10 x 10(4) U/ml rt-PA, a concentration of 60 x 10(4) U/ml rt-PA had no effect on synthesis. These results indicate that UK and pro-UK each inhibit platelet function, but a high concentration of rt-PA enhances platelet aggregability. This finding may at least in part contribute to the high incidence of reocclusion after initially successful thrombolysis with rt-PA.
Yamada
Y
Y
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Furui
H
H
Furumichi
T
T
Yamauchi
K
K
Yokota
M
M
Saito
H
H
D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D010960:Plasminogen Activators / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011994:Recombinant Proteins; D012008:Recurrence; D013929:Thromboxane B2 / Q000096:biosynthesis; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D013929:Thromboxane B2; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator