Journal article
Kinetics and mechanics of clot contraction are governed by the molecular and cellular composition of the blood
Blood, v 127(1)
07 Jan 2016
PMID: 26603837
Featured in Collection : UN Sustainable Development Goals @ Drexel
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, redblood 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, Ca2+, the integrin alpha(IIb)beta(3), 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.
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Details
- Title
- Kinetics and mechanics of clot contraction are governed by the molecular and cellular composition of the blood
- Creators
- Valerie Tutwiler - University of PennsylvaniaRustem I. Litvinov - University of PennsylvaniaAndrey P. Lozhkin - Kazan Federal UniversityAlina D. Peshkova - Kazan Federal UniversityTatiana Lebedeva - University of PennsylvaniaFazoil I. Ataullakhanov - HemaCore Ltd., Moscow, RussiaKara L. Spiller - Drexel UniversityDouglas B. Cines - University of PennsylvaniaJohn W. Weisel - University of Pennsylvania
- Publication Details
- Blood, v 127(1)
- Publisher
- Amer Soc Hematology
- Number of pages
- 11
- Grant note
- R01 HL090774; T32 HL007971; HL090774; R56 HL090774 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) T32 H10791 / PHS HHS; United States Department of Health & Human Services; United States Public Health Service R01HL090774 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000369281300024
- Scopus ID
- 2-s2.0-84955459560
- Other Identifier
- 991019169525404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Hematology