Squeezing for Life – Properties of Red Blood Cell Deformability

Abstract

Deformability is an essential feature of blood cells (RBCs) that enables them to travel through even the smallest capillaries of the human body. Deformability is a function of (i) structural elements of cytoskeletal proteins, (ii) processes controlling intracellular ion and water handling and (iii) membrane surface-to-volume ratio. All these factors may be altered in various forms of hereditary hemolytic anemia, such as sickle cell disease, thalassemia, hereditary spherocytosis and hereditary xerocytosis. Although mutations are known as the primary causes of these congenital anemias, little is known about the resulting secondary processes that affect RBC deformability (such as secondary changes in RBC hydration, membrane protein phosphorylation, and RBC vesiculation). These secondary processes could, however, play an important role in the premature removal of the aberrant RBCs by the spleen. Altered RBC deformability could contribute to disease pathophysiology in various disorders of the RBC. Here we review the current knowledge on RBC deformability in different forms of hereditary hemolytic anemia and describe secondary mechanisms involved in RBC deformability.

Red blood cells: the forgotten player in hemostasis and thrombosis

“…This review will briefly summarize what is currently known about the involvement of RBCs in hemostasis and thrombosis and its underappreciated importance. RBCs increase blood viscosity because of a rise in hematocrit, an increase in RBC aggregation or a decrease in RBC deformability (increasing flow resistance) Pro [2][3][4][5] Conversely, anemia is associated with low blood viscosity and bleeding tendency as a result of reduced platelet margination toward endothelium and enhanced NO availability Anti [2][3][4][5] RBCs undergo shear-dependent reversible aggregation mediated by plasma proteins (mainly fibrinogen and immunoglobulins) and/or local osmotic gradient Pro [14][15][16][70][71][72][73][74] RBCs with increased rigidity occlude small vessels Pro [11,12] Deformability of RBCs reduces frictional resistance to flow Anti [8,[11][12][13]] RBCs maintain biconcave shape and a high surface-to-volume ratio as a result of cytoskeleton and water/ions balance Pro or anti [5] RBCs migrate to the center of blood flow and push platelets toward the endothelium (margination) in a hematocrit-and shear-dependent manner Pro [59][60][61] Effects on platelet reactivity RBCs increase platelet adhesion and aggregation by release of ADP and thromboxane A 2 Pro [66,67] RBCs form aggregates with platelets via adhesive molecules (ICAM-4 and fibrinogen with aIIbb3)…”

MYH9‐related disease mutations cause abnormal red blood cell morphology through increased myosin‐actin binding at the membrane

“…However, both HS and HE affect RBC deformability in ektacytometry, while MYH9 ‐RD does not. Many RBC membrane disorders cause changes in membrane protein levels or protein modifications . While we did not detect changes in major membrane proteins or in phosphorylation of the NMIIA heavy or light chains, future proteomic or phospho‐proteomic studies may detect changes that contribute to the changes in RBC shape and CBC indices in MYH9 ‐RD.…”

Advances in understanding the pathogenesis of red cell membrane disorders

“…A case in point is ektacytometry, which is a powerful tool for the diagnosis of DHS1. However, the co‐inheritance of conditions, such as beta‐thalassemia trait and splenectomy, may modify the ektacytometry curve shape thereby leading to a misdiagnosis (Da Costa et al , ; Lazarova et al , ; Huisjes et al , ; Zaninoni et al , ; Llaudet‐Planas et al , ). The flow‐cytometric osmotic fragility test is a new method for the diagnosis of HS, HE and DHS in combination with eosin‐5'‐maleimide testing.…”