Elevated hematocrit enhances platelet accumulation following vascular injury

Bethany L. Walton, Marcus Lehmann, Tyler Skorczewski, Lori A. Holle, Joan D Beckman, Jeremy A. Cribb, Micah J. Mooberry, Adam R. Wufsus, Brian C. Cooley, Jonathan W. Homeister, Rafal Pawlinski, Michael R. Falvo, Nigel S. Key, Aaron L. Fogelson, Keith B. Neeves, Alisa S. Wolberg

Research output: Contribution to journalArticle

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Abstract

Red blood cells (RBCs) demonstrate procoagulant properties in vitro, and elevated hematocrit is associated with reduced bleeding and increased thrombosis risk in humans. These observations suggest RBCs contribute to thrombus formation. However, effects of RBCs on thrombosis are difficult to assess because humans and mice with elevated hematocrit typically have coexisting pathologies. Using an experimental model of elevated hematocrit in healthy mice, we measured effects of hematocrit in 2 in vivo clot formation models. We also assessed thrombin generation, platelet-thrombus interactions, and platelet accumulation in thrombi ex vivo, in vitro, and in silico. Compared with controls, mice with elevated hematocrit (RBCHIGH) formed thrombi at a faster rate and had a shortened vessel occlusion time. Thrombi in control and RBCHIGH mice did not differ in size or fibrin content, and there was no difference in levels of circulating thrombin-antithrombin complexes. In vitro, increasing the hematocrit increased thrombin generation in the absence of platelets; however, this effect was reduced in the presence of platelets. In silico, direct numerical simulations of whole blood predicted elevated hematocrit increases the frequency and duration of interactions between platelets and a thrombus.Whenhumanwhole blood was perfused over collagen at arterial shear rates, elevating the hematocrit increased the rate of platelet deposition and thrombus growth. These data suggest RBCs promote arterial thrombosis by enhancing platelet accumulation at the site of vessel injury. Maintaining a normal hematocrit may reduce arterial thrombosis risk in humans.

Original languageEnglish (US)
Pages (from-to)2537-2546
Number of pages10
JournalBlood
Volume129
Issue number18
DOIs
StatePublished - May 4 2017

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Vascular System Injuries
Platelets
Hematocrit
Thrombosis
Blood Platelets
Blood
Erythrocytes
Thrombin
Computer Simulation
Direct numerical simulation
Pathology
Fibrin
Shear deformation
Collagen
Cells
Theoretical Models
Hemorrhage

Cite this

Walton, B. L., Lehmann, M., Skorczewski, T., Holle, L. A., Beckman, J. D., Cribb, J. A., ... Wolberg, A. S. (2017). Elevated hematocrit enhances platelet accumulation following vascular injury. Blood, 129(18), 2537-2546. https://doi.org/10.1182/blood-2016-10-746479

Elevated hematocrit enhances platelet accumulation following vascular injury. / Walton, Bethany L.; Lehmann, Marcus; Skorczewski, Tyler; Holle, Lori A.; Beckman, Joan D; Cribb, Jeremy A.; Mooberry, Micah J.; Wufsus, Adam R.; Cooley, Brian C.; Homeister, Jonathan W.; Pawlinski, Rafal; Falvo, Michael R.; Key, Nigel S.; Fogelson, Aaron L.; Neeves, Keith B.; Wolberg, Alisa S.

In: Blood, Vol. 129, No. 18, 04.05.2017, p. 2537-2546.

Research output: Contribution to journalArticle

Walton, BL, Lehmann, M, Skorczewski, T, Holle, LA, Beckman, JD, Cribb, JA, Mooberry, MJ, Wufsus, AR, Cooley, BC, Homeister, JW, Pawlinski, R, Falvo, MR, Key, NS, Fogelson, AL, Neeves, KB & Wolberg, AS 2017, 'Elevated hematocrit enhances platelet accumulation following vascular injury', Blood, vol. 129, no. 18, pp. 2537-2546. https://doi.org/10.1182/blood-2016-10-746479
Walton BL, Lehmann M, Skorczewski T, Holle LA, Beckman JD, Cribb JA et al. Elevated hematocrit enhances platelet accumulation following vascular injury. Blood. 2017 May 4;129(18):2537-2546. https://doi.org/10.1182/blood-2016-10-746479
Walton, Bethany L. ; Lehmann, Marcus ; Skorczewski, Tyler ; Holle, Lori A. ; Beckman, Joan D ; Cribb, Jeremy A. ; Mooberry, Micah J. ; Wufsus, Adam R. ; Cooley, Brian C. ; Homeister, Jonathan W. ; Pawlinski, Rafal ; Falvo, Michael R. ; Key, Nigel S. ; Fogelson, Aaron L. ; Neeves, Keith B. ; Wolberg, Alisa S. / Elevated hematocrit enhances platelet accumulation following vascular injury. In: Blood. 2017 ; Vol. 129, No. 18. pp. 2537-2546.
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AU - Homeister, Jonathan W.

AU - Pawlinski, Rafal

AU - Falvo, Michael R.

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