What Causes Rouleaux Formation in Blood?

Blood circulates throughout the body, delivering oxygen and nutrients while removing waste. Disruptions in its composition can lead to observable changes, offering clues about underlying physiological states or medical conditions.

What is Rouleaux?

Rouleaux refers to the stacking of red blood cells (RBCs) in a linear, coin-like fashion. They appear similar to stacks of coins when viewed under a microscope. Normally, red blood cells circulate individually, but in rouleaux, they adhere face-to-face.

The Core Mechanism: Plasma Protein Changes

The primary cause of rouleaux formation lies in alterations to the concentration of proteins within the blood plasma. Red blood cells possess a negative charge on their surface, known as the zeta potential. This negative charge causes the cells to repel each other, preventing them from clumping.

However, when levels of certain large plasma proteins increase, they reduce this repulsive force. These proteins, particularly acute phase proteins like fibrinogen and some immunoglobulins, are positively charged. They bind to the negatively charged surface of the red blood cells, effectively neutralizing or diminishing the zeta potential.

With reduced repulsive forces, red blood cells come into closer contact. Their biconcave disc shape allows them to stick together and form linear stacks. This process is distinct from agglutination, where red blood cells clump irregularly due to antibody interactions. The increased protein concentration also raises plasma viscosity, further contributing to the environment conducive to rouleaux formation.

Underlying Medical Conditions

Several medical conditions and physiological states can lead to the plasma protein changes that promote rouleaux formation. Inflammatory processes, both acute and chronic, are common culprits. During inflammation, the body produces increased amounts of acute phase proteins, such as fibrinogen and C-reactive protein, as part of its immune response. These elevated proteins then facilitate rouleaux.

Certain blood cancers, particularly multiple myeloma, are strongly associated with rouleaux. In multiple myeloma, abnormal plasma cells produce excessive amounts of monoclonal proteins, a type of immunoglobulin. These high levels of immunoglobulins significantly alter the plasma protein composition, leading to pronounced rouleaux formation. Other conditions involving high immunoglobulin levels, such as Waldenström’s macroglobulinemia, also cause rouleaux.

Physiological changes, like those occurring during pregnancy, can also contribute. Pregnancy involves an increase in fibrinogen synthesis, which can enhance red blood cell aggregation and lead to rouleaux. Severe anemia, where there is a decreased red blood cell count, can also sometimes be associated with rouleaux, though it is not a direct cause but rather a finding in some anemic patients with underlying protein imbalances. Additionally, conditions like diabetes mellitus can lead to rouleaux formation.