Thrombogenicity of Lipoprotein A: Laboratory Study Defining the Prothrombotic Effects of Lipoprotein A

Overview

Brief summary: Lipoprotein a (Lp(a)) is an independent risk factor for cardiovascular and cerebrovascular disease. Traditionally, the pathogenic role of Lp(a) has been linked to the atherogenic process given its similarity to low density lipoprotein (LDL), however there is a potential for prothrombotic tendencies given its resemblance to plasminogen. The emerging evidence suggests that the prothrombotic properties of Lp(a) contribute not only to arterial but also to venous thrombosis. Lp(a) has the potential to participate in thrombogenesis via several mechanisms: probable platelet aggregation and activation, increased expression of plasminogen activator inhibitor - 1, and reduced production of plasmin. Prior data suggests that Lp(a), can also modify fibrin clot permeability and its susceptibility to lysis. These observations have potentially important implications in patients with a history of myocardial infarction, stroke and venous thromboembolic disease. The investigators propose to conduct a proof-of-concept study to assess the prothrombotic effects of Lp(a), using both quantitative and qualitative assessment of thrombosis, in particular analysing clot structure and dynamics.

Thrombogenicity of Lp(a) study is a two-centre, open-label, non-randomised, observational laboratory study defining the prothrombotic effects of Lp(a). The study is aimed to answer the question of effect of LP(a) on thrombus formation in patients with previous history of myocardial infarction. Blood thrombogenicity in patients with previous history of myocardial infarction will be studied using the following techniques: i) Badimon chamber: this will assess thrombogenicity of flowing blood. Approximately 50 mls of blood drawn from the antecubital vein, will be passed through the chamber at 37 degrees C. The chamber will contain strips of porcine aorta denuded of its intima layer to promote thrombosis. The resulting thrombus will be fixed in formalin, stained with haematoxylin/eosin and the amount of thrombus quantified using the Image ProPlus software. ii) Scanning electron microscope (SEM): A sample of the resulting thrombus from the above experiment will be gold stained and the thrombus ultrastructure analysed under SEM. This will allow for examination and analysis of the microstructure morphology and characterization of the thrombus. iii) Thromboelastography (TEG) is a comprehensive assay of the overall clotting process, a method used to provide a global assessment of whole blood, coagulation and clot lysis.