Absence of inhibition by lipoprotein (a) inhibition of tPA induced thrombolysis in a patient's plasma milieu.
The increase in Lp(a) is strongly correlated with premature coronary artery disease. The Apo(a) has striking homology to plasminogen. It was found in an in vitro purified system that Lp(a) competes with both plasminogen and tissue-type plasminogen activator (tPA) for fibrin binding sites, thus resulting in a decrease in fibrin-dependent plasminogen activation. In this study, plasma fibrinolysis was studied in a young patient who had a consistently high level of Lp(a) (198 mg/dl) and had suffered from cerebral thrombophlebitis 12 months previously. The patient had normal levels of plasma plasminogen and fibrinogen. The euglobulin lysis time before and after venous occlusion was not prolonged, and after the addition of tPA to the patient's plasma or whole blood, the clot lysis time was normal. The same result was obtained when the patient's plasma was depleted of Lp(a) before clotting. When the patient's plasma serpins were inhibited, plasminogen activation by tPA in the presence of several fibrin concentrations was normal, suggesting that the formation of the ternary complex tPA - plasminogen - fibrin was not inhibited by the presence of high levels of Lp(a). It is concluded that a consistently high level of Lp(a) in this patient did not inhibit tPA-dependent fibrinolysis, and the thrombotic episode was not therefore related to deficient thrombolysis.
Lu
H
H
INSERM U 150, Hôpital Lariboisière, Paris, France.
Bruckert
J
J
Soria
J
J
Li
H
H
de Gennes
J L
JL
Legrand
A
A
Peynet
J
J
Soria
C
C
D000328:Adult; D001054:Apolipoproteins A / Q000235:genetics; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D002542:Intracranial Embolism and Thrombosis / Q000097:blood*; D008055:Lipids / Q000097:blood; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000235:genetics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000235:genetics; D010958:Plasminogen / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D001054:Apolipoproteins A; D008055:Lipids; D017270:Lipoprotein(a); D008074:Lipoproteins; D010446:Peptide Fragments; D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator