The plasma protein fibrinogen stabilizes clusters of red blood cells in microcapillary flows

TL;DR

This study demonstrates that fibrinogen and dextran promote stable red blood cell clusters in microcapillaries, affecting blood flow and potentially influencing microvascular health even at normal fibrinogen levels.

Contribution

The paper reveals that fibrinogen stabilizes red blood cell clusters in microcapillaries, challenging previous assumptions about rouleaux disaggregation at high shear rates.

Findings

Fibrinogen and dextran induce robust RBC clusters in microcapillaries.

Stable aggregates form even at low hematocrits and normal fibrinogen levels.

Persistent RBC clusters may influence microvascular blood flow and health.

Abstract

The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule network and in arterioles at low shear rates or stasis. Thanks to an excellent agreement between combined experimental and numerical approaches, we show that despite the large shear rates present in microcapillaries, the presence of either fibrinogen or the synthetic polymer dextran leads to an enhanced formation of robust clusters of red blood cells, even at haematocrits as low as 1%. Robust aggregates are shown to exist in microcapillaries even for fibrinogen concentrations within the healthy physiological range. These persistent aggregates should strongly affect cell distribution and blood perfusion in the microvasculature, with putative implications for blood disorders even within apparently asymptomatic subjects.