Abstract
Polyhedral erythrocytes, named polyhedrocytes, are formed in contracted blood clots and thrombi, as a result of compression by activated contractile platelets pulling on fibrin. This deformation was shown to be mechanical in nature and polyhedrocytes were characterized using light and electron microscopy. Through three-dimensional reconstruction, we quantified the geometry of biconcave, intermediate, and polyhedral erythrocytes within contracting blood clots. During compression, erythrocytes became less oblate and more prolate than the biconcave cells and largely corresponded to convex, irregular polyhedra with a total number of faces ranging from 10 to 16. Faces were polygons with 3 to 6 sides. The majority of the faces were quadrilaterals, though not all sides were straight and not all faces were flat. There were no changes in the surface area or volume. These results describe the gradual natural deformation of erythrocytes as a part of compaction into a tightly packed array that is an important but understudied component of mature blood clots and thrombi.
Highlights
Erythrocytes were commonly believed to be passive bystanders in the processes involved in blood clotting, but recent studies revealed that they play a more influential role in both hemostasis and thrombosis[1,2]
Because contraction of blood clots imposes mechanical load on erythrocytes[6], we used four independent imaging modalities to assess the shape change of erythrocytes packed into the core of contracted clots
Unlike the above imaging techniques, confocal microscopy allowed for the visualization of three-dimensional images of either biconcave cells (Fig. 1G) or polyhedrocytes (Fig. 1H), where all sides of the cell could be observed and quantified; the characterization of these images are described in more detail in following sections
Summary
Erythrocytes were commonly believed to be passive bystanders in the processes involved in blood clotting, but recent studies revealed that they play a more influential role in both hemostasis and thrombosis[1,2]. The reduced extent of clot contraction, implying a larger volume and a less compact structure, may aggravate arterial and venous thrombosis due to increased obstructiveness and perhaps propensity of a thrombus to rupture and embolize[11,12] This remarkable polyhedral shape of erythrocytes, first described by Gottlob et al.[13] and rediscovered later[10,12,14,15], is a natural morphological form of erythrocytes in addition to echinocytes, acanthocytes, spheroechinocytes, ovalocytes, elliptocytes, stomatocytes, and more[16]. We were able to determine that purely mechanical forces that mimic those generated by contracting platelets can reproduce formation of a variety of polyhedron-like erythrocytes These erythrocytes taking on a fully polyhedral shape have an average of 13 faces with between 3–6 sides on each face. Gaining a more detailed understanding of the formation of mechanically compressed polyhedral-like erythrocytes has the potential to shed light on the biomechanical and biological properties of contracted intravascular or extravascular clots and thrombi
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