title: Hematocrit and flow rate regulate the adhesion of platelets to von Willebrand factor.
abstract: Primary hemostasis and blood clotting is known to be influenced by the red blood cell volume fraction (hematocrit) in blood. Depressed or elevated levels of red blood cells can lead to vascular perfusion problems ranging from bleeding to thrombus formation. The early stage of hemostasis and thus blood clotting in all vessel sections from the arterial to the venous system involves the adhesion of platelets to von Willebrand factor. Here we present experimental and theoretical results showing that the adhesion probability of platelets to von Willebrand factor is strongly and nonlinearly dependent on hematocrit and flow rate. Interestingly, the actual binding forces are not markedly different, which suggest that the origin of such behavior is in the distribution of platelets. Using hydrodynamic simulations of a simple model, we explicitly show that the higher the hematocrit and the flow rate, the larger the amount of platelets residing close to the wall. Our simulation results, which are in excellent agreement with the experimental observations, explain why such phenomena occur. We believe that the nonhomogeneous red blood cell distribution as well as the shear dependent hydrodynamic interaction is key for the accumulation of platelets on the vessel wall. The work we present here is an important step forward from our earlier work on single molecules and extends into the collective cellular behavior of whole blood. It sheds new light on the correlation between hematocrit and the initial steps in hemostasis and thrombosis, and outlines advances for the treatment of vascular diseases associated with high levels of red blood cells. These results are not only highly relevant for the field of hemostasis and the physics of blood clotting but are also of powerful impact in applied science most obviously in drug delivery and colloidal science.
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02138, USA.
authors.forename: Hsieh
authors.initials: H
authors.lastname: Chen
authors.affiliation: Experimental Physics I, Biological Physics Group, University of Augsburg, 86159 Augsburg, Germany ; Department of Transfusion Medicine/Haemostaseology, University Clinic Munich, LMU, 80337 Munich, Germany.
authors.forename: Jennifer I
authors.initials: JI
authors.lastname: Angerer
authors.affiliation: Department of Transfusion Medicine/Haemostaseology, University Clinic Munich, LMU, 80337 Munich, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Napoleone
authors.affiliation: Baxter Innovations GmbH, Vienna, Austria.
authors.forename: Armin J
authors.initials: AJ
authors.lastname: Reininger
authors.affiliation: Department of Dermatology, Venereology, and Allergology, Experimental Dermatology, Medical Faculty Mannheim, Heidelberg Ruprecht-Karls-University, 68167 Mannheim, Germany.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Schneider
authors.affiliation: Experimental Physics I, Biological Physics Group, University of Augsburg, 86159 Augsburg, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Wixforth
authors.affiliation: Department of Mechanical Engineering, Boston University, Boston, Massachusetts 02215, USA.
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Schneider
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02138, USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Alexander-Katz