PB1275 - Hemostasis after vessel injury occurs under high shear conditions

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Alexandra A. Yakusheva, PhD

Post Doc
Etablissement Français du Sang GRAND EST
Strasbourg, Alsace, France

Co-Author(s)

KB

Kirill R. Butov

Ph.D. Candidate
Dmitry Rogachev Pediatric Hematology and Immunology Hospital
Moscow, Moskva, Russia
GB

Georgii Bykov

Student
Center for Theoretical Problems of Physicochemical Pharmacology
Moscow, Moskva, Russia
GZ

Gábor Závodszky

Professor
Computational Science Lab, Faculty of Science, Institute for Informatics, University of Amsterdam
Amsterdam, Noord-Holland, Netherlands
FA

Fazoil I. Ataullakhanov

visiting professor
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Philadelphia, Pennsylvania, United States
MP

Mikhail A. Panteleev

Director
Center for Theoretical Problems of Physico-Chemical Pharmacology
Moscow, Moskva, Russia
PM

Pierre Mangin

Research Director
Université de Strasbourg, INSERM, EFS Grand Est, BPPS UMR-S1255, FMTS, F-67065 Strasbourg, France
Strasbourg, Alsace, France

Background: Blood flow is a major regulator of hemostasis and thrombosis. The current view is that intermediate flows occur in healthy vessels, while high shear levels are reached notably during thrombosis. Targeting high shear has been proposed as an innovative strategy to selectively block thrombosis with a minor impact on hemostasis. The shear rates occurring at the edge of the lesion on a healthy vessel are unknown.

Aims: To measure experimentally the shear rates occurring in wounds in a context relevant to hemostasis.

Methods: Two models of vessel puncture in human and mice were developed and characterized. Doppler probes were used to measure blood flow in the vessels throughout the hemostatic process, and ComSol software allowed to recalculate shear rates and elongational flows in the wound. We used a model with a catheter in which the shear rate was calculated by applying Poiseuille’s equation with volumetric rates of blood loss.

Results: Shear rates at the edge of the wound reached high values the medians of which were 22,000 s-1, 25,000 s-1 and 7,000 s-1 after puncture of the carotid artery, aorta or saphenous vein, respectively. These results were confirmed in a human venous puncture model where shear rates in an implanted catheter in the cubital vein reached 2,000-27,000 s-1. In all models, elevated levels of elongational flows exceeding 1,000 s-1 were found. The shear rates steeply decreased with the increase in injury size which was explained by the low hydrodynamic resistance of the injuries compared to the resistance of the downstream vessel network.

Conclusion(s): The relative vessel-wound resistance determines the decrease of shear rate with increase in injury size. Various types of lesions in small and large mouse and human vessels result in high levels of shear rates and elongational flows, which are therefore not specific to arterial thrombosis, but also relevant to hemostasis.