M. G. Bartley1, N. G. Vigneshwar1, J. R. Coleman1, J. M. Samuels1, A. Sauaia1, A. Banerjee1, C. Silliman3,4, E. E. Moore1,2 1University Of Colorado Denver,Surgery,Aurora, CO, USA 2Denver Health Medical Center,Surgery,Aurora, CO, USA 3Bonfils Blood Center,Research Laboratory,Denver, CO, USA 4University Of Colorado Denver,Pediatrics,Aurora, CO, USA
Introduction: Lipoprotein (a) [Lp(a)] is a composite of low-density lipoprotein (LDL), apolipoprotein B-100 (ApoB) and apolipoprotein A [Apo(a)]. Apo(a) contains a serine protease and multiple kringle domains, specifically kringle IV and V that share homology to the fibrinolytic zymogen plasminogen. Previous studies have shown Lp(a) can bind to endothelial cell surfaces inhibiting pericellular plasminogen activation. The majority of Lp(a) studies have focused on the association between atherosclerotic risk and elevated plasma levels with limited data on coagulative properties. We hypothesize that elevated levels of Lp(a) will induce fibrinolytic shutdown via inhibition of plasminogen.
Methods: Exogenous Lp(a) low (20mg/dl) and high dose(60mg/dl) physiologic concentrations, tissue plasminogen activator(tPA) were added to whole blood (WB) samples from healthy volunteers(n=8). Samples were assessed using citrated native thromboelastography(TEG). Fibrinolysis was initiated by adding tPA to samples containing either whole blood alone or with low dose (20mg/dl) or high dose (60mg/dl) of Lp(a). The following TEG measurements were recorded: clot initiation (R time, fibrin polymerization (angle) and clot strength [maximum amplitude (MA) clot lysis time 30 minutes after reaching MA (LY30)].
Results: LY30 increased significantly with the addition of tPA in whole blood(WB 1.2% vs WB+tPA11.7 p=0.002) but was unaffected by low or high dose Lp(a) with tPA (low dose 11.3% p=0.99 vs high dose 7.8% p=0.45). Low dose Lp(a) did not modify coagulation however, high dose Lp(a) prolonged clot initiation (R time), reduced clot formation (angle) and strength (MA) (WB 14.2min vs low 21.1 p=0.93; WB 14.2min vs high dose 99.0min p=0.0001) (WB 54mm vs low dose 49mm p=0.92; WB 54mm vs high dose 26.9mm p=0.005) (WB 40.8 deg vs low dose 33.4 deg p=0.68; WB 40.8 deg vs 11.35 deg p=0.0002).
Conclusion: Lp(a) did not modify fibrinolysis, but high doses produced un anticipated hypocoagulability. The mechanism and clinical implications warrant further investigation.
