In vivo dynamic real-time monitoring and quantification of platelet-thrombus formation Use of a local isotope detector

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 uni que potentially noninvasive system to detect and quantify dynamic thrombus formation in vivo by using a porcine model of carotid artery injury. Thromb us growth was monitored by deposition of autologous In-111-labeled platelet activity over the injured artery by use, of miniaturized gamma detectors a nd Doppler blood flow. Counts were recorded at 2-minute intervals for 2 hou rs. The technique was validated by comparing standard antithrombotic agents against controls. Platelet recruitment was detected before significant cha nge in flow. Thrombus formation, calculated as the area under the curve (pl ateletsxminutesx10(6)), was greatest for control animals (11.76+/-1.28), fo llowed by animals treated with aspirin (6.13+/-0.91, P<0.05), heparin (2.45 +/-0.34, P<0.05), and hirudin (0.2+/-0.01, P<0.01 compared with heparin), T he rate of platelet deposition was assessed as the slope of the curve in th e first 30 minutes (platelets x 10(6) per minute) for the following treatme nt groups of aninlals: control, 3.53+/-0.34; aspirin, 1.67+/-0.34 (P<0.01); heparin, 1.55+/-0.3 (P<0.01); and hirudin, 0.25+/-0.03 (P<0.001). There wa s no statistical difference between heparin and aspirin treatments. Change in flow was assessed as reduction from baseline: control, >99+/-0.34%; aspi rin, 39+/-9.1%; heparin, 36+/-12.5%; and hirudin, 17+/-5.4%. There was no s tatistical difference between the aspirin- and heparin-treated groups. Morp hometric analysis revealed >99+/-0.63% occlusion of the luminal area with t hrombus 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-treat ed group. Assessment of platelet-thrombus formation with this technique was more sensitive than change in now in determining antithrombotic efficacy, and thrombus formation was detected earlier. This study validates a new qua ntitative, sensitive, potentially noninvasive, portable, in vivo monitoring of dynamic thrombus growth, which appears applicable to phase II studies i n humans.