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O5 Exploring the impact of platelet activation on plasmin generation
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O5 Exploring the impact of platelet activation on plasmin generation
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Journal Article
O5 Exploring the impact of platelet activation on plasmin generation
2025
Overview
BackgroundFibrinolysis is the process by which fibrin clots are degraded via the action of plasmin. A novel high throughput plasmin generation (PG) assay has been developed and has potential as a clinical tool. Platelets modulate fibrinolysis through release of the precursor of plasmin, plasminogen, plasminogen activator inhibitor 1 (PAI-1) and thrombin activatable fibrinolysis inhibitor (TAFI). Our work has shown platelets also anchor plasminogen to their surface.AimTo investigate the impact of platelets on PG using a novel assay.MethodPlatelet-rich plasma (PRP) and matched platelet-poor plasma (PPP) was collected from healthy donors. PG was quantified by fluorogenic substrate in plasma (22%) clotted using tissue factor (1 pM), and CaCl2 (16.7 mM) with tissue plasminogen activator (17.8 nM). PRP was analysed ± stimulation with collagen (CRP-XL, 1 µg/ml) and thrombin (TRAP-6, 30 µM) platelet receptor agonists. Fluorescence was read every 20 s for 30 min (37°C). A neutralising antibody to PAI-1 (5 µg/ml); the cofactor for TAFI, thrombomodulin (TM; 20 nM); and inhibitor of TAFIa, carboxypeptidase inhibitor (CPI; 25 µg/ml), were included in some experiments.ResultsUnstimulated PRP reduced the plasmin peak (49.2±2.8 nM) compared to matched PPP (69.1±7.4 nM). In contrast, stimulation of PRP enhanced the plasmin peak (49.2±2.8 nM to 63.7±4.2 nM) and shortened the lag time (4.6±0.06 min to 3.4±0.1 min) compared to unstimulated PRP. Neutralising PAI-1 had no impact on PG. TM significantly reduced PG to a similar degree in matched PPP (11.3±2.7 nM) and PRP (12.8±3.2 nM) and could be recovered to baseline with CPI.ConclusionThe PG assay was not sensitive to the inhibitory impact of platelet-derived PAI-1. The inhibitory effect of the TM-TAFIa complex was comparable in stimulated PRP and PPP. Interestingly, inclusion of platelet agonists significantly augmented PG, potentially by facilitating assembly of profibrinolytic proteins on the activated platelet membrane.
Publisher
BMJ Publishing Group LTD
Subject
