In vivo real time monitoring and quantification of platelet-thrombus formation: Validation of a locally applied non invasive system

Current methods for monitoring thrombus growth are invasive, provide only single time point data and rely on flow changes as a surrogate of thrombus formation. Our aim was to validate a unique, potentially non invasive system to detect and quantify dynamic thrombus formation in vivo using a porcine model of carotid artery injury. Methods: Thrombus growth was monitored by deposition of autologous ¹¹¹In-labelled platelet activity over the injured artery using miniaturised γ detectors (17x10x10 mm) and Doppler blood flow. Counts were recorded at two minute intervals for two hours. Standard anti-thrombotic agents (aspirin, heparin, hirudin) were compared to saline treated controls. Results: Platelet recruitment was detected before significant change in flow. Thrombus formation, calculated as area under the curve, was greatest for control(con) animals (11.7±1.28) followed by aspirin(asa) (6.13±0.34, P<0.05) heparin(hep) (2.45±0.34, P<0.05) and hirudin(hir) (0.2±0.01, P<0.01 ). Change in flow, assessed as percent reduction from baseline, was con >99±0.34, asa 39±9.1, hep 36±12.5, hir 17±5.4. There was no statistical difference between asa and hep groups if flow was used to assess thrombus formation. Morphometric analysis of thrombus formation revealed controls to have >99±0.63% occlusion of the luminal area, asa 43±14.3%, hep 30±5.6% and hir <10±1.8%. Conclusions: Assessment of platelet-thrombus using this technique was more sensitive than change in flow in determining antithrombotic efficacy and detected thrombus growth earlier. This study validates a new quantitative, sensitive, potentially non-invasive, portable, in vivo monitoring of dynamic thrombus growth which appears applicable to phase II studies in humans.