In Vivo Dynamic Real-Time Monitoring and Quantification of Platelet-Thrombus Formation

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Abstract
—Current methods for monitoring thrombosis and thrombus growth are invasive and provide only single–time-point data. Animal models rely mainly on flow changes as a surrogate of thrombus formation. Our aim was to validate a unique potentially noninvasive system to detect and quantify dynamic thrombus formation in vivo by using a porcine model of carotid artery injury. Thrombus growth was monitored by deposition of autologous 111In-labeled platelet activity over the injured artery by use of miniaturized gamma detectors and Doppler blood flow. Counts were recorded at 2-minute intervals for 2 hours. The technique was validated by comparing standard antithrombotic agents against controls. Platelet recruitment was detected before significant change in flow. Thrombus formation, calculated as the area under the curve (platelets×minutes×106), was greatest for control animals (11.7±1.28), followed by animals treated with aspirin (6.13±0.91, PPP6 per minute) for the following treatment groups of animals: control, 3.53±0.34; aspirin, 1.67±0.34 (PPP99±0.34%; aspirin, 39±9.1%; heparin, 36±12.5%; and hirudin, 17±5.4%. There was no statistical difference between the aspirin- and heparin-treated groups. Morphometric analysis revealed >99±0.63% occlusion of the luminal area with thrombus for the control group, 43±14.3% for the aspirin-treated group, 30±5.6% for the heparin-treated group, and <10±1.8% for the hirudin-treated group. Assessment of platelet-thrombus formation with this technique was more sensitive than change in flow in determining antithrombotic efficacy, and thrombus formation was detected earlier. This study validates a new quantitative, sensitive, potentially noninvasive, portable, in vivo monitoring of dynamic thrombus growth, which appears applicable to phase II studies in humans.

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