title: Kinetics and mechanics of clot contraction are governed by the molecular and cellular composition of the blood.
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 because of 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 nonmuscle myosin II, red blood cells (RBCs), fibrin(ogen), factor XIIIa (FXIIIa), and thrombin on the kinetics and mechanics of the contraction process. Clot contraction is composed of 3 sequential phases, each characterized by a distinct rate constant. Thrombin, Ca(2+), the integrin αIIbβ3, myosin IIa, FXIIIa cross-linking, and platelet count all promote 1 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.
authors.affiliation: School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Valerie
authors.initials: V
authors.lastname: Tutwiler
authors.affiliation: Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: Rustem I
authors.initials: RI
authors.lastname: Litvinov
authors.affiliation: Kazan Federal University, Kazan, Russia;
authors.forename: Andrey P
authors.initials: AP
authors.lastname: Lozhkin
authors.affiliation: Kazan Federal University, Kazan, Russia;
authors.forename: Alina D
authors.initials: AD
authors.lastname: Peshkova
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Lebedeva
authors.affiliation: HemaCore Ltd., Moscow, Russia.
authors.forename: Fazoil I
authors.initials: FI
authors.lastname: Ataullakhanov
authors.affiliation: School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA;
authors.forename: Kara L
authors.initials: KL
authors.lastname: Spiller
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Cines
authors.affiliation: Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;
authors.forename: John W
authors.initials: JW
authors.lastname: Weisel
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000166:cytology* / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D003018:Clot Retraction / Q000502:physiology*; D003432:Cross-Linking Reagents; D004912:Erythrocytes / Q000378:metabolism; D026122:Factor XIIIa / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D006487:Hemostasis; D006801:Humans; D007700:Kinetics; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D012212:Rheology; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology*
chemical_list: D003432:Cross-Linking Reagents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D005337:Fibrin; D026122:Factor XIIIa; D013917:Thrombin; D024507:Nonmuscle Myosin Type IIA; D002118:Calcium