Erythrocyte fragility

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Erythrocyte fragility
MeSH D009996

Erythrocyte fragility refers to the propensity of erythrocytes (red blood cells, RBC) to hemolyse (rupture) under stress. It can be thought of as the degree or proportion of hemolysis that occurs when a sample of red blood cells are subjected to stress (typically physical stress, and most commonly osmotic and/or mechanical stress). Depending on the application as well as the kind of fragility involved, the amount of stress applied and/or the significance of the resultant hemolysis may vary.[ citation needed ]

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When multiple levels of stress are applied to a given population/sample of cells, a fragility profile can be obtained by measuring the relative or absolute extent of hemolysis existing at each such level, [1] in addition to finding one or more single-number indexes [2] (either measured directly or interpolated) associated with particular respective levels of hemolysis and/or corresponding stress. Fragility testing can be useful to assess cells' ability (or lack thereof) to withstand sustained or repeated stress. Moreover, it can be used to assess how fragility itself varies under different or changing environmental or stress conditions, during or prior to the inducement of the hemolysis. Low fragility is often termed "stability," though technically stability refers to cells' resistance to both stress-induced lysis and spontaneous auto-lysis.[ citation needed ]

Erythrocyte osmotic fragility

Osmotic fragility (OF) refers to the degree or proportion of hemolysis that occurs when a sample of red blood cells are subjected to osmotic stress by being placed in a hypotonic solution. Osmotic fragility is affected by various factors, including membrane composition and integrity as well as the cells' sizes or surface-area-to-volume ratios. [3] [4] [5]

The osmotic fragility test is common in hematology, and is often performed to aid with diagnosis of diseases associated with RBC membrane abnormalities. Some diseases linked to increased OF include hereditary spherocytosis and hypernatremia, while some linked to decreased OF include chronic liver disease, iron deficiency anemia, thalassemia, hyponatremia, polycythemia vera, hereditary xerocytosis, [6] and sickle cell anemia after splenectomy. [7]

New approaches to testing OF are under development to better facilitate its use in disease diagnosis and screening, such as by utilizing microfluidic devices along with cell counting. [8]

Erythrocyte mechanical fragility

Mechanical fragility (MF) refers to the degree or proportion of hemolysis that occurs when a sample of red blood cells are subjected to mechanical stress, such as (typically) some kind of shear stress. Yet unlike with osmotic fragility, no single approach for testing mechanical fragility has yet gained sufficient acceptance to enable standardization. [9] This has led to some insurance companies not currently covering the test. [10]

Uses of erythrocyte mechanical fragility can include diagnostic testing, [11] calibrations to aid comparisons of hemolysis caused by blood-handling devices, [9] or assessment of sublethal (i.e., non-hemolysing) damage caused to cells from devices that manipulate blood (such as for dialysis [12] or intraoperative autotransfusion [13] ). It can also help in assessing damage of stored RBC product [14] (so-called "storage lesion"), leading to applications in blood transfusion and blood banking.

It's also notable that there can be a qualitative difference between a mechanical fragility test involving a comparatively lower energy stress, such as by agitating one or more beads in the presence of the sample (a common approach [15] ), versus a higher energy stress, such as by applying ultrasound to the sample. [16] The difference is that the lower-energy category of stress can more prominently reflect cell membrane properties, whereas the higher-energy category largely reflects other properties like hemoglobin viscosity and cell size. Viscous or fluidic-mechanical stresses can be of either sort.[ citation needed ]

Susceptibility to hemolysis from causes other than osmotic or mechanical forces are not as common, but may sometimes be referred to in terms of fragility or stability. For example, photons or radicals can induce hemolysis.Erythrocytes/RBC may also be tested for related membrane properties aside from fragility, including erythrocyte deformability and cell morphology. Morphology can be measured by indexes which characterize shape changes of differences among cells. Deformability testing involves measuring the degree or ease of cells' contortion or shape change under a given level of applied force - or some indirect inference of the like. Other related red blood cell properties can include adhesion and aggregation, which along with deformability are often classed as RBC "flow properties."[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Red blood cell</span> Oxygen-delivering blood cell and the most common type of blood cell

Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek erythros 'red' and kytos 'hollow vessel', with -cyte translated as 'cell' in modern usage), are the most common type of blood cell and the vertebrate's principal means of delivering oxygen (O2) to the body tissues—via blood flow through the circulatory system. RBCs take up oxygen in the lungs, or in fish the gills, and release it into tissues while squeezing through the body's capillaries.

<span class="mw-page-title-main">Hemolysis</span> Rupturing of red blood cells and release of their contents

Hemolysis or haemolysis, also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid. Hemolysis may occur in vivo or in vitro.

<span class="mw-page-title-main">Spherocytosis</span> Medical condition

Spherocytosis is the presence of spherocytes in the blood, i.e. erythrocytes that are sphere-shaped rather than bi-concave disk shaped as normal. Spherocytes are found in all hemolytic anemias to some degree. Hereditary spherocytosis and autoimmune hemolytic anemia are characterized by having only spherocytes.

<span class="mw-page-title-main">Hereditary spherocytosis</span> Medical condition

Hereditary spherocytosis (HS) is a congenital hemolytic disorder, wherein a genetic mutation coding for a structural membrane protein phenotype leads to a spherical shaping of erythrocytic cellular morphology. As erythrocytes are sphere-shaped (spherocytosis), rather than the normal biconcave disk-shaped, their morphology interferes with these cells' abilities to be flexible during circulation throughout the entirety of the body - arteries, arterioles, capillaries, venules, veins, and organs. This difference in shape also makes the red blood cells more prone to rupture under osmotic and/or mechanical stress. Cells with these dysfunctional proteins are degraded in the spleen, which leads to a shortage of erythrocytes resulting in hemolytic anemia.

<span class="mw-page-title-main">Paroxysmal nocturnal hemoglobinuria</span> Medical condition

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. There is ongoing research into other key features of the disease, such as the high incidence of venous blood clot formation. Research suggests that PNH thrombosis is caused by both the absence of GPI-anchored complement regulatory proteins on PNH platelets and the excessive consumption of nitric oxide (NO).

<span class="mw-page-title-main">Hemolytic anemia</span> Medical condition

Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels or elsewhere in the human body (extravascular). This most commonly occurs within the spleen, but also can occur in the reticuloendothelial system or mechanically. Hemolytic anemia accounts for 5% of all existing anemias. It has numerous possible consequences, ranging from general symptoms to life-threatening systemic effects. The general classification of hemolytic anemia is either intrinsic or extrinsic. Treatment depends on the type and cause of the hemolytic anemia.

<span class="mw-page-title-main">Mean corpuscular hemoglobin concentration</span> Measure of hemoglobin concentration in red blood cells

The mean corpuscular hemoglobin concentration (MCHC) is a measure of the concentration of hemoglobin in a given volume of packed red blood cell.

The direct and indirect Coombs tests, also known as antiglobulin test (AGT), are blood tests used in immunohematology. The direct Coombs test detects antibodies that are stuck to the surface of the red blood cells. Since these antibodies sometimes destroy red blood cells they can cause anemia; this test can help clarify the condition. The indirect Coombs test detects antibodies that are floating freely in the blood. These antibodies could act against certain red blood cells; the test can be carried out to diagnose reactions to a blood transfusion.

<span class="mw-page-title-main">Codocyte</span> Type of red blood cell

Codocytes, also known as target cells, are red blood cells that have the appearance of a shooting target with a bullseye. In optical microscopy these cells appear to have a dark center surrounded by a white ring, followed by dark outer (peripheral) second ring containing a band of hemoglobin. However, in electron microscopy they appear very thin and bell shaped. Because of their thinness they are referred to as leptocytes. On routine smear morphology, some people like to make a distinction between leptocytes and codocytes- suggesting that in leptocytes the central spot is not completely detached from the peripheral ring, i.e. the pallor is in a C shape rather than a full ring.

<span class="mw-page-title-main">Hereditary elliptocytosis</span> Medical condition

Hereditary elliptocytosis, also known as ovalocytosis, is an inherited blood disorder in which an abnormally large number of the person's red blood cells are elliptical rather than the typical biconcave disc shape. Such morphologically distinctive erythrocytes are sometimes referred to as elliptocytes or ovalocytes. It is one of many red-cell membrane defects. In its severe forms, this disorder predisposes to haemolytic anaemia. Although pathological in humans, elliptocytosis is normal in camelids.

Southeast Asian ovalocytosis is a blood disorder that is similar to, but distinct from hereditary elliptocytosis. It is common in some communities in Malaysia and Papua New Guinea, as it confers some resistance to cerebral Falciparum Malaria.

<span class="mw-page-title-main">Hereditary stomatocytosis</span> Medical condition

Hereditary stomatocytosis describes a number of inherited, mostly autosomal dominant human conditions which affect the red blood cell and create the appearance of a slit-like area of central pallor (stomatocyte) among erythrocytes on peripheral blood smear. The erythrocytes' cell membranes may abnormally 'leak' sodium and/or potassium ions, causing abnormalities in cell volume. Hereditary stomatocytosis should be distinguished from acquired causes of stomatocytosis, including dilantin toxicity and alcoholism, as well as artifact from the process of preparing peripheral blood smears.

<span class="mw-page-title-main">Hereditary pyropoikilocytosis</span> Medical condition

Hereditary pyropoikilocytosis (HPP) is an autosomal recessive form of hemolytic anemia characterized by an abnormal sensitivity of red blood cells to heat and erythrocyte morphology similar to that seen in thermal burns or from prolonged exposure of a healthy patient's blood sample to high ambient temperatures. Patients with HPP tend to experience severe hemolysis and anemia in infancy that gradually improves, evolving toward typical elliptocytosis later in life. However, the hemolysis can lead to rapid sequestration and destruction of red cells. Splenectomy is curative when this occurs.

Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens, therefore they also commonly act on allogenic RBCs. AIHA is a relatively rare condition, with an incidence of 5–10 cases per 1 million persons per year in the warm-antibody type and 0.45 to 1.9 cases per 1 million persons per year in the cold antibody type. Autoimmune hemolysis might be a precursor of later onset systemic lupus erythematosus.

Cold agglutinin disease (CAD) is a rare autoimmune disease characterized by the presence of high concentrations of circulating cold sensitive antibodies, usually IgM and autoantibodies that are also active at temperatures below 30 °C (86 °F), directed against red blood cells, causing them to agglutinate and undergo lysis. It is a form of autoimmune hemolytic anemia, specifically one in which antibodies bind red blood cells only at low body temperatures, typically 28–31 °C.

Normocytic anemia is a type of anemia and is a common issue that occurs for men and women typically over 85 years old. Its prevalence increases with age, reaching 44 percent in men older than 85 years. The most common type of normocytic anemia is anemia of chronic disease.

Erythrocyte deformability refers to the ability of erythrocytes to change shape under a given level of applied stress, without hemolysing (rupturing). This is an important property because erythrocytes must change their shape extensively under the influence of mechanical forces in fluid flow or while passing through microcirculation. The extent and geometry of this shape change can be affected by the mechanical properties of the erythrocytes, the magnitude of the applied forces, and the orientation of erythrocytes with the applied forces. Deformability is an intrinsic cellular property of erythrocytes determined by geometric and material properties of the cell membrane, although as with many measurable properties the ambient conditions may also be relevant factors in any given measurement. No other cells of mammalian organisms have deformability comparable with erythrocytes; furthermore, non-mammalian erythrocytes are not deformable to an extent comparable with mammalian erythrocytes. In human RBC there are structural support that aids resilience in RBC which include the cytoskeleton- actin and spectrin that are held together by ankyrin.

Hemolytic jaundice, also known as prehepatic jaundice, is a type of jaundice arising from hemolysis or excessive destruction of red blood cells, when the byproduct bilirubin is not excreted by the hepatic cells quickly enough. Unless the patient is concurrently affected by hepatic dysfunctions or is experiencing hepatocellular damage, the liver does not contribute to this type of jaundice.

Cell biomechanics a branch of biomechanics that involves single molecules, molecular interactions, or cells as the system of interest. Cells generate and maintain mechanical forces within their environment as a part of their physiology. Cell biomechanics deals with how mRNA, protein production, and gene expression is affected by said environment and with mechanical properties of isolated molecules or interaction of proteins that make up molecular motors.

<span class="mw-page-title-main">Sucrose lysis test</span>

The sucrose lysis test is a diagnostic laboratory test used for diagnosing paroxysmal nocturnal hemoglobinuria (PNH), as well as for hypoplastic anemias and any hemolytic anemia with an unclear cause. The test works by using sucrose, which creates a low ionic strength environment that allows complement to bind to red blood cells. In individuals with PNH, some red blood cells are especially vulnerable to lysis caused by complement. The test may also produce suspicious results in other hematologic conditions, including megaloblastic anemia and autoimmune hemolytic anemia. False-negative results can occur when complement activity is absent in the serum. A simpler alternative called the sugar water test also involves mixing blood with sugar and observing for hemolysis, using the same principle as the sucrose lysis test.

References

  1. ↑ http://spherocytosis.info/2012/01/osmotic-fragility-test/
  2. ↑ DE KRETSER AJ, WALDRON HA (1963). "The Mechanical Fragility of the Red Cell in Patients with Lead Poisoning". Br J Ind Med. 20 (4): 316–9. doi:10.1136/oem.20.4.316. PMC   1039189 . PMID   14072624.
  3. ↑ Rodak, Bernadette F.; et al. (2007). Hematology: clinical principles and applications. Elsevier Health Sciences. p. 291. ISBN   978-1-4160-3006-5.
  4. ↑ Fischbach, Frances Talaska; Dunning, Marshall Barnett (2008). A manual of laboratory and diagnostic tests (8th ed.). Lippincott Williams & Wilkins. p. 116. ISBN   978-0-7817-7194-8.
  5. ↑ Greer, John P.; et al., eds. (2008). Wintrobe's clinical hematology. Lippincott Williams & Wilkins. p. 805. ISBN   978-0-7817-6507-7.
  6. ↑ "How is hereditary spherocytosis (HS) differentiated from hereditary xerocytosis (HX)?".
  7. ↑ "Osmotic Fragility is a test for hereditary spherocytosis - ClinLab Navigator". clinlabnavigator.com.
  8. ↑ Chen, Hongda; Ye, Datian; Wu, Hongkai; Peng, Fei; Li, Jing; Su, Jing; Li, Lei (2012-07-30). "A microfluidic platform for osmotic fragility test of red blood cells". RSC Advances. 2 (18): 7161–7165. Bibcode:2012RSCAd...2.7161L. doi:10.1039/C2RA20051A.
  9. 1 2 ASAIO J. 2005 May-Jun;51(3):194-201. Mechanical fragility calibration of red blood cells.
  10. ↑ "Obsolete and Unreliable Tests and Procedures". aetna.com.
  11. ↑ http://www.upmc.com/healthcare-professionals/physicians/Documents/lab-fee-schedule.pdf [ bare URL PDF ]
  12. ↑ ASAIO J. 2002 Jan-Feb;48(1):34-8. In vitro evaluation of hemolysis and sublethal blood trauma in a novel subcutaneous vascular access system for hemodialysis.
  13. ↑ Yazer M. H.; Waters J. H.; Elkin K. R.; Rohrbaugh M. E.; Kameneva M. V. (2008). "A comparison of hemolysis and red cell mechanical fragility in blood collected with different cell salvage suction devices". Transfusion. 48 (6): 1188–1191. doi:10.1111/j.1537-2995.2008.01670.x. PMID   18346016. S2CID   28610759.
  14. ↑ Vox Sang. 2010 Nov;99(4):325-31. The use of the mechanical fragility test in evaluating sublethal RBC injury during storage.
  15. ↑ Handbook of Hemorheology and Hemodynamics, edited by Oğuz K. Baskurt, Max R. Hardeman, Ph.D., Michael W. Rampling, Ph.D., Herbert J. Meiselman
  16. ↑ Hemolysis by ultrasound: a comparative study of the osmotic and ultrasonic fragility tests. Scandinavian journal of haematology, Supplementum, no. 29, 1976.
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