Plasminogen activator inhibitor antigen

Abstract

Plasminogen activator inhibitor type 1 (PAI-1) antigen assays are not as widely used as PAI activity assays (see Chapter 18) and clinical experience with these assays is limited. The presence in plasma of several distinct forms of PAI-1, and the fact that the PAI-1 antigen assays developed to date measure these forms with different efficacy, render interpretation and comparison of PAI-1 antigen data more complicated. Four distinct forms of PAI-1 have been identified: active, latent, t-PA- or u-PA-bound and proteolytically degraded. For PAI-1 antigen measurements in human plasma the active, latent and t-PA-bound forms are the most important ones. Conformational changes in the PAI-1 molecule upon conversion from active to latent1 or upon reaction with PAs are considerable and many monoclonal antibodies preferentially recognize one form of PAI-1. As a consequence the results of PAI antigen assay are critically dependent on the assay being used (Table 19.1). In human blood two distinct compartments for PAI-1 have been identified: plasma and platelets. In healthy individuals the amount of PAI-1 antigen in platelets is approximately ten-fold higher than in plasma. However, as platelet PAI-1 is only 5–10% active, and plasma PAI-1 50–80%, the contribution of platelets to total PAI-1 activity in blood is only approximately 60%2. To specificially measure plasma PAI-1 antigen, the contribution of platelets should be kept as low as possible.