Rouleaux formation happens when either fibrinogens or globulins are present at high levels in the blood, although at times it may be caused by incorrect blood smear preparation when blood is placed on a slide for microscopic examination. The formation causes red blood cells to be stacked on top of each other.
Without considering the possibility of error in sample preparation, a high-protein concentration in the blood causes the red blood cells to clump together. The presence of high amounts of the plasma proteins increases the erythrocyte sedimentation rate (ESR). Aside from this, the natural discoid structure of red blood cells has a flat surface with enough surface area for cells to bond with each other. All of these conditions result in the cells sticking together to form rolls, hence the term rouleau.
From a chemical viewpoint, fibrinogens are acute-phase proteins attracted to sialic acid intrinsically found on the superficial membrane of red blood cells. The interaction between the two compounds may be aggravated by anemia or hypovolemia, which create a high ratio of red blood cells to the volume of plasma.
Symptoms and related diseases that may cause rouleaux formation include multiple myeloma, connective tissue abnormalities, inflammation, infections, diabetes mellitus and certain cancers.