Comparative Ultrastructural Analyses of Mouse, Rabbit, and Human Platelets and Fibrin Networks

Abstract

Platelets and fibrin play an important role in the coagulation process, where they are involved in the maintenance of hemostasis. Fibrin dysfunction is associated with the development of vascular complications, while proneness to the formation of tight and rigid fibrin networks is independently associated with thrombotic disease. Here we investigate the ultrastructure of human, rabbit, and mouse platelets and fibrin networks, using the scanning electron microscope. Human and rabbit fibrin and platelets, with regards to morphology as well as size of major and minor fibers compare well with each other. However, mouse fibers are much thinner and form a flimsy branching network. Platelet aggregate morphology of all three species compare well with each other. We conclude that rabbit platelet and fibrin networks could be used successfully when studying the effect of pharmaceutical products in preclinical trials, when looking at the effects of these products on morphology and ultrastructure.

Carbon monoxide: Anticoagulant or procoagulant?

“…Platelets appear to respond to CO in a similar fashion among human and rodent studies [10][11][12]16,21,22], but plasmatic coagulation also appears to be enhanced in humans, rats and rabbits [48,[51][52][53][54][55][56][57][58][67][68][69]. In an effort to reveal potential sources of specie specific differences, one may consider the differences in thrombus ultrastructure between humans, rabbits, mice and rats [94,95]. Images of PRP thrombi obtained with SEM reveal a remarkable similarity between humans and rabbits, and a marked difference in structure from mice and rats as displayed (Fig.…”

“…5. ), which was generated using methods mentioned previously [94,95]. Humans and rabbit thrombi have a less dense matrix, composed of thick and thin fibrin polymers, whereas rodent clots have a more woven, matted structure.…”

“…How these species-specific differences in ultrastructure impact on plasmatic coagulation kinetics and, ultimately, clinical hemostatic response to CO is Nielsen et al 19 19 Human and rabbit thrombus fibrin polymer formation is remarkably similar, whereas both rodent thrombi markedly differ from human and rabbit. Details of how these data are generated have been previously cited [94,95]. White bar = 1 μm.…”

Intrapleural Adenoviral Delivery of Human Plasminogen Activator Inhibitor–1 Exacerbates Tetracycline-Induced Pleural Injury in Rabbits

“…These changes collectively promote intrapleural fibrin deposition, which rapidly organizes, with the infiltration of fibrinous intrapleural adhesion by collagen fibrils within 2 to 3 days of an intrapleural administration of TCN (25,26). A recent report demonstrated the close similarity of rabbit fibrin structure to human fibrin, which provides another advantage for the use of rabbit models of fibrotic injury in preclinical testing (29).In the present study, we induced the selective, transient overexpression of human PAI-1 (hPAI-1) and lacZ in the pleural mesothelium of rabbits, delivering the target gene using a recombinant adenovirus. By overexpressing hPAI-1, we sought to further our understanding of the role of active PAI-1 in pleural injury.…”

“…These changes collectively promote intrapleural fibrin deposition, which rapidly organizes, with the infiltration of fibrinous intrapleural adhesion by collagen fibrils within 2 to 3 days of an intrapleural administration of TCN (25,26). A recent report demonstrated the close similarity of rabbit fibrin structure to human fibrin, which provides another advantage for the use of rabbit models of fibrotic injury in preclinical testing (29).…”