RBCs regulate platelet function and hemostasis under shear conditions through biophysical and biochemical means
Publication Date
1-1-2024
Document Type
Article
Publication Title
Blood
DOI
10.1182/blood.2024023887
Abstract
Red blood cells (RBCs) have been hypothesized to support hemostasis by facilitating platelet margination and releasing platelet-activating factors such as adenosine 5′-diphosphate (ADP). Significant knowledge gaps remain regarding how RBCs influence platelet function, especially in (patho)physiologically relevant hemodynamic conditions. Here, we present results showing how RBCs affect platelet function and hemostasis in conditions of anemia, thrombocytopenia, and pancytopenia and how the biochemical and biophysical properties of RBCs regulate platelet function at the blood and vessel wall interface and in the fluid phase under flow conditions. We found that RBCs promoted platelet deposition to collagen under flow conditions in moderate (50 × 103/μL) but not severe (10 × 103/μL) thrombocytopenia in vitro. Reduction in hematocrit by 45% increased bleeding in mice with hemolytic anemia. In contrast, bleeding diathesis was observed in mice with a 90% but not with a 60% reduction in platelet counts. RBC transfusion improved hemostasis by enhancing fibrin clot formation at the site of vascular injury in mice with severe pancytopenia induced by total body irradiation. Altering membrane deformability changed the ability of RBCs to promote shear-induced platelet aggregation. RBC-derived ADP contributed to platelet activation and aggregation in vitro under pathologically high shear stresses, as observed in patients supported by left ventricular assist devices. These findings demonstrate that RBCs support platelet function and hemostasis through multiple mechanisms, both at the blood and vessel wall interface and in the fluidic phase of circulation.
Funding Number
T32 HL007093
Funding Sponsor
National Institutes of Health
Department
Chemical and Materials Engineering
Recommended Citation
Debbie Jiang, Katie L. Houck, Lydia Murdiyarso, Harrison Higgins, Nicole Rhoads, Sophia K. Romero, Rosemary Kozar, Angelo Nascimbene, Terry B. Gernsheimer, Zyrina Alura C. Sanchez, Anand K. Ramasubramanian, Reheman Adili, and Jing fei Dong. "RBCs regulate platelet function and hemostasis under shear conditions through biophysical and biochemical means" Blood (2024). https://doi.org/10.1182/blood.2024023887
