Evaluation of lipoprotein(a) as a prothrombotic factor: progress from bench to bedside.
OBJECTIVE
Since the homology between apolipoprotein(a) (apo(a)) and plasminogen was discovered in 1987, the role of lipoprotein(a) (Lp(a)) as an inhibitor of the normal fibrinolytic role of plasmin(ogen) has been a major research focus. In this review we summarize recent basic research aimed at identifying mechanisms by which Lp(a) can either inhibit fibrinolysis or promote coagulation, as well as recent clinical studies of Lp(a) as a risk factor for thrombosis either in the presence or absence of atherosclerosis.


RESULTS
It has recently been reported that the inhibition of plasminogen activation by apo(a) results from the interaction of apo(a) with the ternary complex of tissue-type plasminogen activator, plasminogen and fibrin, rather than competition of apo(a) and plasminogen for binding sites on fibrin. Lp(a) species containing smaller apo(a) isoforms bind more avidly to fibrin and are better inhibitors of plasminogen activation. Recent clinical studies have provided strong evidence that Lp(a), either alone or in synergy with other thrombotic risk factors, significantly increases the risk of venous thromboembolism and ischemic stroke.


CONCLUSIONS
Lp(a) both attenuates fibrinolysis, through inhibition of plasminogen activation, and promotes coagulation, through alleviation of extrinsic pathway inhibition. Further basic and clinical studies are required to more clearly define the role of Lp(a) in thrombotic disorders, and to determine the extent to which thrombotic risk is dependent on apo(a) isoform size.
Marcovina
Santica M
SM
Department of Medicine, University of Washington, Seattle, Washington 98103, USA. smm@u.washington.edu
Koschinsky
Marlys L
ML
D000818:Animals; D001779:Blood Coagulation Factors / Q000502:physiology*; D002986:Clinical Trials as Topic; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D017270:Lipoprotein(a) / Q000502:physiology*; D010958:Plasminogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D001779:Blood Coagulation Factors; D017270:Lipoprotein(a); D010958:Plasminogen; D010959:Tissue Plasminogen Activator