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Kinetics and mechanics of clot contraction are governed by the molecular and cellular composition of the blood

Valerie Tutwiler, Rustem I. Litvinov, Andrey P. Lozhkin, Alina D. Peshkova, Tatiana Lebedeva, Fazoil I. Ataullakhanov, Kara L. Spiller, Douglas B. Cines and John W. Weisel

Key points

  • Clot contraction has three phases differentially affected by platelet and fibrin mechanics, RBCs compaction and various blood components.

  • A new dynamic quantitative clot contraction assay can reveal novel aspects of formation and evolution of hemostatic clots and thrombi.

Abstract

Platelet-driven blood clot contraction (retraction) is thought to promote wound closure and secure hemostasis while preventing vascular occlusion. Notwithstanding its importance, clot contraction remains a poorly understood process, partially due to the lack of methodology to quantify its dynamics and requirements. We used a novel automated optical analyzer to continuously track in vitro changes in the size of contracting clots in whole blood and in variously reconstituted samples. Kinetics of contraction was complemented with dynamic rheometry to characterize the viscoelasticity of contracting clots. This combined approach enabled investigation of the coordinated mechanistic impact of platelets, including non-muscle myosin II, red blood cells, fibrin(ogen), factor XIIIa, and thrombin on the kinetics and mechanics of the contraction process. Clot contraction is comprised of three sequential phases, each characterized by a distinct rate constant. Thrombin, Ca2+, the integrin αIIbβ3, myosin IIa, factor XIIIa-crosslinking, and platelet count all promote one or more phases of the clot contraction process. In contrast, RBCs impair contraction and reduce elasticity, while increasing the overall contractile stress generated by the platelet-fibrin meshwork. A better understanding of the mechanisms by which blood cells, fibrin(ogen), and platelet-fibrin interactions modulate clot contraction may generate novel approaches to reveal and to manage thrombosis and hemostatic disorders.

  • Submitted May 26, 2015.
  • Accepted November 17, 2015.