Why do thrombi stop growing? – fibrin polymerization may limit clot growth
Abstract number: PP-WE-394
Kamocka1 M., Xu2 Z., Mu3 J., Liu3 X., Alber2 M., Chen3 D., Rosen1 E.D.
11Medical and Molecular Genetics, Indiana Univesity School of Medicine, Indianapolis 22Mathematics 33Computer Sciences, Notre Dame, Notre Dame, USA
How-to-cite Kamocka M, Xu Z, Mu J, Liu X, Alber M, Chen D, Rosen ED. Why do thrombi stop growing? – fibrin polymerization may limit clot growth. Journal of Thrombosis and Haemostasis 2009; Volume 7, Supplement 2: Abstract PP-WE-394
Current models of thrombogenesis include the binding of platelets in flowing blood onto the surface of the developing thrombus. The newly incorporated platelets release factors promoting further platelet activation and provide a surface supporting surface-dependent coagulation reactions. Since the new surface of the developing clot provides a prothrombotic environment for continued growth, it is not obvious why thrombi stop growing.
We recently developed a vascular injury model using multiphoton intravital microscopy. Following laser-induced injury of mouse mesenteric venules, the developing thrombus is monitored by collecting stacks of images of optical planes through the thrombus. Multichannel image acquisition enables one to monitor fluorescently labeled fibrinogen and platelets. By including fluorescently labeled dextran in the blood one can monitor flow as well as unlabeled cells that appear as black holes by excluding the labeled dextran. This system produces high resolution structural information revealing the changing, heterogeneous sub-domain structure of the developing thrombus.
Using newly developed image processing algorithms we are able to follow the changing composition of the thrombus surface. Thrombus growth is greatest when the thrombus surface is composed primarily of platelets. The cessation of clot growth corresponds with an increasing percentage of fibrin. At later times the thrombus surface is covered by cells. We hypothesize that fibrin polymerization on the surface of the developing clot provides a barrier between resting platelets in the flowing blood and the prothrombotic surface of platelets within the thrombus. Thrombin binding sites on fibrin may also interfere with the diffusion of thrombin generated on platelets within the clot to the new thrombus surface. Thus, fibrin polymerization not only increases thrombus stability but may also inhibit continuous thrombus growth.
Disclosure of interest: none declared.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
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