Quantifying Platelet Margination in Diabetic Blood Flow

Abstract

Patients with type 2 diabetes mellitus (T2DM) develop thrombotic abnormalities strongly associated with cardiovascular diseases. In addition to the changes of numerous coagulation factors such as elevated levels of thrombin and fibrinogen, the abnormal rheological effects of red blood cells (RBCs) and platelets flowing in blood are crucial in platelet adhesion and thrombus formation in T2DM. An important process contributing to the latter is the platelet margination. We employ the dissipative particle dynamics method to seamlessly model cells, plasma, and vessel walls. We perform a systematic study on the RBC and platelet transport in cylindrical vessels by considering different cell shapes, sizes and RBC deformabilities in healthy and T2DM blood, as well as variable flowrates and hematocrit. In particular, we use cellular-level RBC and platelet models with parameters derived from patient-specific data and present a sensitivity study. We find T2DM RBCs, which are less deformable compared to normal RBCs, lower the transport of platelets toward the vessel walls whereas platelets with higher mean volume (often observed in T2DM) lead to enhanced margination. Furthermore, increasing the flowrate or hematocrit enhances platelet margination. We also investigated the effect of platelet shape and observed a non-monotonic variation with the highest near-wall concentration corresponding to platelets with moderate aspect ratio of 0.38. We examine the role of white blood cells (WBCs), whose count is increased notably in T2DM patients. We find that WBC rolling or WBC adhesion tend to decrease platelet margination due to hydrodynamic effects. To the best of our knowledge, such simulations of blood including all blood cells have not been performed before, and our quantitative findings can help separate the effects of hydrodynamic interactions from adhesive interactions, and potentially shed light on the associated pathological processes in T2DM such as increased inflammatory response, platelet activation and adhesion, and ultimately thrombus formation. METHODSWe employ dissipative particle dynamics (DPD) to model whole blood flow, i.e. plasma, RBCs, platelets and WBCs, in 40-micron diameter vessels. DPD is a coarse-grained analog of molecular dynamics, where each particle represents a lump of molecules that interacts with other particles through soft pairwise forces. In addition to blood plasma modeled by collections of free DPD particles, the membrane of suspending cells including RBCs, platelets, and WBCs is constructed by a 2D triangulated network with N v vertices (DPD particles).These vertices are connected by N s elastic bonds to impose proper membrane mechanics. More details of hydrodynamic interactions between DPD particles, and models for blood cells are presented in Appendix A. We also validated systematically the DPD model by simulating the margination of spherical particles of different sizes in blood flow and compared against recent experimental measurements (52). The validation results are given in Appendix B.

Testosterone Therapy: An Assessment of the Clinical Consequences of Changes in Hematocrit and Blood Flow Characteristics

“…This results in highly heterogeneous haematocrit distributions in the microcirculation that cause local variations in viscosity and flow resistance. This has been demonstrated in vivo[53] and in recent microfluidic studies of blood flow[54,55].In addition to the Fåhraeus effect the particulate nature of blood is also responsible for phenomena such as leucocyte and platelet margination[56] where these smaller cells are observed to migrate towards the vessel wall. Increased haematocrit could lead to more interactions between erythrocytes and leucocytes or platelets promoting margination.…”