Letters to the Editor 1059 Platelets and lipoprotein(a) in retinal vein occlusion: Mutual targets for aspirin therapy Giuseppe Lippi 1 , Massimo Franchini 2 , GiovanniTargher 3 1 Sezione di Chimica e Microscopia Clinica, Dipartimento di Scienze Morfologico-Biomediche, Università degli Studi diVerona,Verona, Italy; 2 Servizio di Immunoematologia e Trasfusione, Azienda Ospedaliera diVerona,Verona, Italy; 3 Sezione di Endocrinologia e Malattie del Metab- olismo, Dipartimento di Scienze Biomediche e Chirurgiche, Università degli Studi diVerona, Italy Correspondence to: Prof. Giuseppe Lippi, MD Sezione di Chimica e Microscopia Clinica Dipartimento di Scienze Morfologico-Biomediche Università degli Studi diVerona Ospedale Policlinico G.B. Rossi Piazzale Scuro, 10 37134 –Verona, Italy Tel.: +39 045 8074516, Fax: +39 045 8201889 E-mail: ulippi@tin.it Received February 11, 2007 Accepted after revision March 5, 2007 Prepublished online May 3, 2007 doi:10.1160/TH07–02–0108 Thromb Haemost 2007; 97: 1059–1060 Dear Sir, Retinal vein occlusion (RVO), the second commonest sight- threatening vascular disorder, is a severe pathology character- ized by sectoral intraretinal hemorrhages, retinal ischemia, reti- nal exudates and macular edema. We read with interest the recent editorial of Fateh-Moghadam et al. (1) on the potential effective- ness of antiplatelet therapy in patients with RVO. Despite its fre- quency, the pathogenesis and risk factors of RVO are not com- pletely understood, and treatments are unsatisfactory due to the inclusion of therapeutical strategies that have not been tested by large, well-designed, prospective, randomised controlled trials (2–4). The effectiveness of the traditional therapeutical arma- mentarium, including isovolaemic haemodilution, radial optic neurotomy, optic nerve decompression or arteriovenous crossing sheathotomy is limited and is frequently unsuitable for the pres- ence of severe comorbidities, since most patients who develop RVO are older than 50 and the vast majority has associated hy- pertension, diabetes mellitus, cardiovascular, renal or pulmon- ary disorders (3, 4). Argon-laser-photocoagulation can prevent the development and treat neovascularizations successfully, but is unable to improve visual function in most cases (5). Finally, vitrectomy combined with either intravenous thrombolysis or ar- teriovenous sheathotomy may offer promise for central and branch RVO, though this approach still needs further evaluation in larger trials (6). Basically, the main caveat in the identification of a reliable and effective therapy for this challenging thrombotic disease is our limited understanding of major contributing factors and pa- thogenesis. It has previously been suggested that platelets may provide a trigger mechanism for venous thrombosis in the eye when local conditions permit (7). In this respect, the article by Leoncini et al. (8) offers a further substantial contribution to this challenging subject by reporting that activated platelets may play a large role in the pathogenesis of RVO. Besides platelet hyper- reactivity, a variety of additional risk factors have been variably associated with RVO, including systemic disorders (hyperten- sion, diabetes mellitus, atherosclerosis and hypercholesterol- emia), local alterations (increased ocular pressure and open- angle glaucoma) (1, 9), thrombophilic risk factors (factor V Leiden, hyperhomocysteinemia, anticardiolipin antibodies and type 1 plasminogen activator inhibitor) (10–18), and lipopro- tein(a) [Lp(a)]. Lp(a) is an intriguing molecule consisting of a low-density lipoprotein core associated by a disulfide bond to the heterogeneous glycoprotein apolipoprotein(a) [(apo(a)] (19). Due to the high degree of structural homology with plasminogen, apo(a) binds to the lysine-binding sites on fibrin and to mem- brane proteins of endothelial cells and monocytes, displacing plasminogen and inhibiting fibrinolysis (19, 20). Convincing epi- demiological evidence supports a causal role of Lp(a) in several thrombotic disorders, including RVO (21–25) and retinal arterio- lar emboli (26). Since increased fibrin deposition impaired fibri- nolysis (21) and platelet activation (8) are hallmarks of RVO, they can both be considered to be potential targets for specific treat- ments. However, the main question is whether antiplatelet or anti- coagulant therapy would provide the highest benefits in both treatment and secondary prevention of RVO. The study by Leon- cini et al. (8) prompted clinicians to conduct prospective inter- ventional trials in order to evaluate the role of antiplatelet treat- ment regimens in RVO patients. We essentially agree with this proposal. Hypothetically, antiplatelet therapy using aspirin would be effectual not only because it decreases platelet hyperreactivity, but also because it lowers the plasma concentration of Lp(a) and modulates the influence of Lp(a) on platelets. It was proven that aspirin reduces apo(a) production from hepatocytes via reduction of the transcriptional activity of apo(a) gene with suppression of apo(a) mRNA expression (27), and Lp(a) levels may be decreased after treatment with 81 mg/day of aspirin by up to 20% (28), es- pecially in patients at an increased risk of thrombotic disorders for the presence of high Lp(a) plasma concentrations (29). Recent findings also indicate the involvement of various components of Lp(a) on different underlying pathways concerning platelet acti- vation and aggregation (30, 31), and an enhanced response of pla- telets via the protease-activated receptor – thrombin receptor has been documented in the presence of Lp(a) (32). Safe and effective treatments for RVO are currently unavail- able (2), hence it is difficult to draw concrete conclusions on this challenging issue (1, 8). Prospective interventional trials with a greater sample size and reliable clinical endpoints are needed to assess the role of antiplatelet therapy in patients with RVO. For personal or educational use only. No other uses without permission. All rights reserved. Downloaded from www.thrombosis-online.com on 2018-05-18 | ID: 1001066444 | IP: 54.70.40.11