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Clot contraction: compression of erythrocytes into tightly packed polyhedra and redistribution of platelets and fibrin

Douglas B. Cines, Tatiana Lebedeva, Chandrasekaran Nagaswami, Vincent Hayes, Walter Massefski, Rustem I. Litvinov, Lubica Rauova, Thomas J. Lowery and John W. Weisel

Key Points

  • In contracted clots and thrombi, erythrocytes are compressed to close-packed polyhedral structures with platelets and fibrin on the surface.

  • Polyhedrocytes form an impermeable seal to stem bleeding and help prevent vascular obstruction but confer resistance to fibrinolysis.

Abstract

Contraction of blood clots is necessary for hemostasis and wound healing and to restore flow past obstructive thrombi, but little is known about the structure of contracted clots or the role of erythrocytes in contraction. We found that contracted blood clots develop a remarkable structure, with a meshwork of fibrin and platelet aggregates on the exterior of the clot and a close-packed, tessellated array of compressed polyhedral erythrocytes within. The same results were obtained after initiation of clotting with various activators and also with clots from reconstituted human blood and mouse blood. Such close-packed arrays of polyhedral erythrocytes, or polyhedrocytes, were also observed in human arterial thrombi taken from patients. The mechanical nature of this shape change was confirmed by polyhedrocyte formation from the forces of centrifugation of blood without clotting. Platelets (with their cytoskeletal motility proteins) and fibrin(ogen) (as the substrate bridging platelets for contraction) are required to generate the forces necessary to segregate platelets/fibrin from erythrocytes and to compress erythrocytes into a tightly packed array. These results demonstrate how contracted clots form an impermeable barrier important for hemostasis and wound healing and help explain how fibrinolysis is greatly retarded as clots contract.

  • Submitted August 28, 2013.
  • Accepted December 2, 2013.
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