The effects of residual platelets in plasma on plasminogen activator inhibitor-1 and plasminogen activator inhibitor-1-related assays

textabstractDue to controversial evidence in the literature pertaining to the activity of plasminogen activator inhibitor-1 in platelets, we examined the effects of residual platelets present in plasma (a potential pre-analytical variable) on various plasminogen activator inhibitor-1 and plasminogen activator inhibitor-1-related assays. Blood samples were collected from 151 individuals and centrifuged at 352 and 1500 g to obtain plasma with varying numbers of platelet. In a follow-up study, blood samples were collected from an additional 23 individuals, from whom platelet-poor (2000 g), platelet-containing (352 g) and platelet-rich plasma (200 g) were prepared and analysed as fresh-frozen and after five defrost-refreeze cycles (to determine the contribution of in vitro platelet degradation). Plasminogen activator inhibitor-1 activity, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex, plasma clot lysis time, β-thromboglobulin and plasma platelet count were analysed. Platelet α-granule release (plasma β-thromboglobulin) showed a significant association with plasminogen activator inhibitor-1 antigen levels but weak associations with plasminogen activator inhibitor-1 activity and a functional marker of fibrinolysis, clot lysis time. Upon dividing the study population into quartiles based on β-thromboglobulin levels, plasminogen activator inhibitor-1 antigen increased significantly across the quartiles while plasminogen activator inhibitor-1 activity and clot lysis time tended to increase in the 4th quartile only. In the follow-up study, plasma plasminogen activator inhibitor-1 antigen was also significantly influenced by platelet count in a concentration-dependent manner. Plasma plasminogen activator inhibitor-1 antigen levels increased further after complete platelet degradation. Residual platelets in plasma significantly influence plasma plasminogen activator inhibitor-1 antigen levels mainly through release of latent plasminogen activator inhibitor-1 with limited effects on plasminogen activator inhibitor-1 activity, tissue plasminogen activator/plasminogen activator inhibitor-1 complex or plasma clot lysis time. Platelets may however also have functional effects on plasma fibrinolytic potential in the presence of high platelet counts, such as in platelet-rich plasma

Comparison of βTG, PAI-1 assays and CLT according to centrifugation speed in SABPA study.

<p>Comparison of βTG, PAI-1 assays and CLT according to centrifugation speed in SABPA study.</p

PAI-1_act, PAI-1_ag, tPA/PAI-1 complex and CLT according to βTG quartiles in SABPA study group.

<p>PAI-1_act, PAI-1_ag, tPA/PAI-1 complex and CLT according to βTG quartiles in SABPA study group.</p

Spearman rank order correlations of βTG and PAI-1_ag with whole blood, CTAD and citrate plasma platelet count of the follow-up study.

<p>Spearman rank order correlations of βTG and PAI-1_ag with whole blood, CTAD and citrate plasma platelet count of the follow-up study.</p

Design of follow-up study.

<p>Design of follow-up study.</p

Spearman rank order correlations between βTG, PAI-1 assays and CLT in SABPA study group.

<p>Spearman rank order correlations between βTG, PAI-1 assays and CLT in SABPA study group.</p

Spearman rank order correlations between βTG and PAI-1_ag in the respective plasma preparations of the follow-up study.

<p>Spearman rank order correlations between βTG and PAI-1_ag in the respective plasma preparations of the follow-up study.</p

Descriptive statistics of the follow-up study group.

<p>Descriptive statistics of the follow-up study group.</p