Lp(a) was first isolated by Berg in 1963. Lp(a) is a hepatocytes-synthesized lipoprotein structurally related to low-density lipoproteins (LDL) and contains, in addition to cholesterol and apolipoprotein B-100, a surface glycoprotein, apolipoprotein (a) (Apo A), responsible for its characteristic properties; in fact, the primary structure of Apo A is similar to that of plasminogen, a key player in the physiological fibrinolysis. DNA of Apo A and DNA of plasminogen are structurally similar and are both located on chromosome 6. The plasma levels of Lp(a) are genetically determined and extremely variable from one subject to another (from 0.001 to 3g/L), but very stable over life in the same individual. This rate is independent of age, sex, smoking, diet, cholesterol and triglycerides circulating and depends very few on environmental factors. Lp(a) is considered an independent risk factor for thromboembolic diseases. The pathophysiological mechanisms discussed are based on a dual role of Lp(a): an atherogenic role and an antifibrinolytic role; in fact Lp(a) and its cholesterol are taken up by macrophages that become foam cells and colonize the vascular endothelium, thus initiating the process of atherosclerosis. On the other hand, due to the structural analogy between Apo A and plasminogen, Lp(a) presents a striking homology with plasminogen and may therefore compete with binding of plasminogen at fibrin, leading to fibrinolytic system dysfunction. In addition, by inhibiting competitively the binding of plasminogen to its receptors on the surface of endothelial cells, Lp(a) prevents also the activation of plasminogen by t-PA. Due to this interaction with fibrinolytic pathway, Lp(a) has a role in thrombosis in vivo.
Many studies show that elevated levels of Lp(a) constitute a risk factor for coronary and Prostaglandin E2 thromboembolic diseases. The great interindividual variability in plasma levels of Lp(a) precludes defining normal values, but the rate of Lp(a) is generally considered pathological when it exceeds 0.3g/L, which is the threshold value beyond which the risk of heart attack increases. Regarding the risk for RVO, the threshold value could be 0.1g/L according to the literature. In our case, blood levels of Lp(a) were 1.7g/L and they represented the only significantly increased marker of a thrombotic disease. Surprisingly, RVO occurred in a no-smoker, no-hyperlipidemic and normotensive patient. Hypertension, smoking, atherosclerosis and diabetes mellitus are non-specific markers for RVO, whereas dyslipidemia and hyperhomocysteinemia are independent risk factors for the occurrence of recurrent CRVO, as shown by Sodi et al.; in fact, hypercholesterolemia, hypertriglyceridemia, fasting and postmethionine hyperhomocysteinemia are more prevalent in recurrent CRVO patients. Marcucci et al. put in evidence that also vitamins involved in methionine metabolism and alterations in the fibrinolysis pathway (elevated levels of PAI-1, deficiency of protein C, of protein S, of antithrombin III, activated protein C resistance) appear to play a significant role in the pathogenesis of this disease. Elevated levels of soluble endothelial protein C receptor also seem to be an important candidate risk factor for CRVO, as shown by Gumus et al. Lp(a) has been shown to be correlated with cardiovascular disorders and is considered as an emerging thrombophilic risk factor in the pathogenesis of RVO. In fact, circulating concentrations of Lp(a) were found to be significantly different in a large population of RVO patients when compared to healthy subjects, independently from other traditional and emerging risk factors, suggesting that Lp(a) may play an important and independent role in its pathogenesis. Our study found elevated levels of Lp(a) in one patient with ischemic CRVO, confirming the hypothesis that Lp(a) may have an independent role in the pathogenesis of this disease, presumably through its pro-atherogenic and antifibrinolytic action. Plasma levels of Lp(a) mainly depend on genetic factors and very few on environmental factors. This probably explains why the therapeutic methods used against hyperlipoproteinemias usually have no influence on plasma levels of Lp(a) (diet, bile salts chelating resins, HMG CoA reductase, fish oils, fibrates). Nicotinic acid would cause a decrease of almost 34% of the concentration of Lp(a), but only the LDL-apheresis resulted in a decrease of large amplitude. The current lack of effective treatments known to reduce levels of Lp(a) or to fight against the consequences of its pathological elevation makes the determination of systemic Lp(a) currently of limited value in clinical practice.