Effect of recombinant-tissue plasminogen activator, low molecular weight urokinase and unfractionated heparin on platelet aggregation.
We studied the interaction of two thrombolytic agents, recombinant-tissue plasminogen activator (r-TPA) and low molecular weight urokinase (UK), with platelet aggregation in the absence or presence of unfractionated heparin (UH). With platelet rich plasma (PRP), a dose dependent inhibition was seen for both r-TPA and UK. However, this effect was more evident in the presence of r-TPA. UH did not modify this effect. However, it enhanced platelet aggregation induced by ADP and decreased the aggregation induced by collagen (COL) as already shown by us. With washed platelets, only r-TPA decreased platelet aggregation in a dose dependent manner in the presence of COL and only at the highest dose (100 micrograms) in the presence of TH. The presence of ten units of plasminogen (PLG) together with 10 micrograms of r-TPA or 1250 units of UK totally inhibited TH-induced platelet aggregation. UH reversed this effect. In contrast, when COL was the aggregating agent, the inhibition of platelet aggregation in presence of PLG, seems to be further increased by UH. Since UH is an adjunct of thrombolytic therapy to prevent rethrombosis, this double edged sword could partially explain the lack of therapeutic effect in some patients.
Paolini
R
R
Institute of Medical Semeiotics, University of Padua, School of Medicine, Italy.
Casonato
A
A
Boeri
G
G
Luzzatto
G
G
Girolami
A
A
Sasahara
A A
AA
Cella
G
G
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008970:Molecular Weight; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000494:pharmacology*; D001620:beta-Thromboglobulin / Q000378:metabolism
D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D001620:beta-Thromboglobulin; D000244:Adenosine Diphosphate; D006493:Heparin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator