Erythrocytes Normal and Abnormal
Normal mature erythrocytes (discocytes) are band disc-shaped and do not have a nucleus. They may have varying sizes, Shape, or color of red blood cells can be observed on microscopic examination using a Wright or comparable Romanowsky-type are stained. Erythrocytes can get stained in numerous disorders or diseases. exhibit variations in appearance or morphology with effects of pathological conditions.
Variations from the normal can be classified as:
- Variation in size
- Change in shape
- Alteration in color
- Inclusions within the erythrocyte
- Changes in the distribution of erythrocytes in a peripheral blood smear
Certain appearance differences can be deceptive. Changes may be due to appearance resulting from artifacts like precipitated stain or proteins instead of a true erythrocytic disorder. Most deviations in erythrocytes can, however, be traced to specific chemical, physical, or cellular causes. This section it describes the appearance of erythrocytes in peripheral blood smears, the factors related to alterations in morphology, and the related clinical conditions.
Types of Variations in Erythrocyte Size
Normocytic RBCs
A normal erythrocyte has an average diameter of 7.2 mm with a usual variation of 6.8 to 7.5 mm. The extreme size limits are generally considered to be 6.2 to 8.2 mm. This normal size is referred to as normocytic.
Macrocytic RBCs
Erythrocytes may be either larger than normal (macrocytic) Macrocytic erythrocytes exceed the 8.2-mm diameter (MCV > 100 fL). It is further divided into megaloblastic and non-megaloblastic macrocytosis. The former occurs due to defective DNA synthesis, usually due to deficiency in vitamin B12 or folate, resulting in large, oval-shaped RBCs (macro-ovalocytes) with hyper segmented neutrophils. The non-megaloblastic causes are liver disease, alcoholism (which causes lipid membrane alterations), myelodysplastic syndromes (MDS), and hypothyroidism.
Microcytic RBCs
Erythrocytes smaller than normal (microcytic) limit, microcytic erythrocytes are smaller than the average 6.2-mm diameter (MCV < 80 fL). This condition is most frequently related to iron deficiency anemia, the most common cause across the globe, where hemoglobin production decreases leading to decreased cell sizes. Other causes include thalassemias, and anemia of chronic illness,. Sideroblastic anemia due to abnormal heme formation can also have microcytic RBCs. The peripheral blood smears in microcytosis are characterized by RBCs having increased central pallor and variability in size.
Anisocytosis
The general term used in hematology to denote an increased variation in cell size is anisocytosis. Anisocytosis is prominent in severe anemias. Anisocytosis refers to a large disparity in RBC size, identifiable through blood smear and red cell distribution width (RDW) in complete blood counts (CBC). A raised RDW (> 14.5%) indicates a mixture of microcytic and macrocytic populations due to early iron deficiency, combined deficiency states (e.g., iron and B12/folate), or hemoglobinopathies. Emerging literature shows RDW to be a prognostic factor in cardiovascular conditions, chronic kidney disease, and sepsis, representing concomitant inflammation and oxidative stress.
Kinds of Variations in Erythrocyte Shape
Poikilocytes
The overall term for mature erythrocytes with a form other than the typical round, biconcave form upon a stained blood smear, or variations, is poikilocytosis. Poikilocytes can have numerous shapes, yet often mimic everyday items like pencils, teardrops, and eggs. Special names have been assigned to most of them. The terms for particular types of poikilocytes are acanthocytes, blister cells, burr cells, crenated erythrocytes, echinocytes, elliptocytes, keratocytes, ovalocytes, pyknocytes, schistocytes, sickle cells, spiculated erythrocytes, spherocytes, stomatocytes, target cells, and teardrop red blood cells. Many hematologists use a new nomenclature in lieu of current
Acanthocytes
Acanthocytes possess several thorny, spike like projections that are irregularly distributed around the membrane and can be variable in size. In contrast to echinocytes, acanthocytes rarely possess few spicules. A common in two quite distinct illnesses: abetalipoproteinemia
a rare inherited disorder, and spur cell anemia.
Blister cells
Blister cells are red blood cells having or more vacuoles resembling a blister on the skin. This cell has a noticeably thinned portion at the periphery or edge boundary of the cell membrane. The vacuoles can burst. If rupturing does happen, distorted keratocytes and cellular fragments (schistocytes) are These cellular changes are encountered where there’s injury to the membrane (such as severe burns). Blister cells are a result of traumatic interaction between blood vessels and circulating blood such as fibrin deposits. Clinically, increased numbers can be
perceived as caused by pulmonary emboli in a case of sickle cell anemia and microangiopathic hemolytic anemia.
Burr cells
Burr cells are erythrocytes with one or more spiny projections of cellular membrane. The cells are often irregularly shaped or have irregular shapes like a quarter moon. Burr cells are more oval-shaped compared to acanthocytes. Clinically, burr cells are elevated in a collection of anemias, gastric ulcer bleeds, gastric cancer, peptic ulcers, renal insufficiency, deficiency of pyruvate kinase, and uremia. They can also appear as artifacts
Echinocytes (Crenated RBCs)
Echinocytes (crenated red blood cells) are characterized by short, notched, or pyramid-shaped processes that are evenly arranged around the red blood cell membrane. The processes are variable in numbers and appearance. Crenation can be a consequence of the physical loss of intracorpuscular water (consult Chapter 3 for a review of osmosis). Crenation is not associated with any disease states, although this distortion of a red blood cell arises from an osmotic imbalance.
Elliptocytes
Elliptocytes are usually more elongated and narrower compared to megalocytes. Elliptocytes are rod-, cigar-, or sausage-shaped. They are a membrane disorder where the membrane is greatly influenced and loses its integrity. The clinical disorders associated with them are hereditary elliptocytosis, anemias related to malignancy, hemoglobin (Hb) C disease, hemolytic anemias (deficiency anaemia, pernicious anaemia, sickle cell trait.
Schistocytes, or Helmet Cells
Schistocytes, or helmet cells, are commonly the large scooped out portion of a cell (Fig. 6.12) resulting from a bursting blister cell and are produced by the physical process of fragmentation. The fragments are created within the spleen and intravascular fibrin clots.
Keratocytes
Keratocytes are partially deformed, uncut erythrocytes. The two horn-shaped spicules are caused by a bursting vacuole. Typically, the cell resembles a half-moon or spindle. These are found in conditions like disseminated (diffuse) intravascular coagulation (DIC).
Knizocytes
Knizocytes are shaped like a pinched bottle. They are found in hemolytic anemias, such as hereditary spherocyt.
Leptocytes
Leptocytes are similar to codocytes (target cells) except for the fact that the inner, central part remains not entirely separated from the outer membrane. This form of target cell has a clinical correlation with hepatic diseases, iron deficiency anemia, and thalassemia.
Ovally macrocytes (megalocytes)
Ovally shaped macrocytes (megalocytes) are oval-shaped or egg-shaped (Fig. 6.13). These cells, while having a comparable appearance to elliptocytes, are macrocytic with a rounder and plumper appearance. Elliptocytes, in contrast, would have a more normal cell-volume size. elevations in this abnormality They occur in vitamin B12 and folate deficiency and can also be seen in erythrocytes in the stage of reticulocytes.
Pyknocytes
Pyknocytes are irregularly shaped, contracted red blood cells resembling burr cells. They are found in acute, severe hemolytic anemia; glucose-6-phosphate dehydrogenase deficiency of G6PD; hereditary deficiency of lipoproteins; can occur in small quantities in the first 2 to 3 months of life in infantile pyknocytes.
Schistocytes (Schizocytes)
Schistocytes (schizocytes) are irregularly shaped, small pieces of erythrocytes. Since these are formed due to the disruption of a red blood cell, the schistocyte would be somewhat smaller than a normal red blood cell and would appear more red. An increased presence of schistocytes can be noticed in hemolytic anemias secondary to burns and prosthetic devices renal transplant rejections.
Sickle cells (drepanocytes)
Sickle cells (drepanocytes) resemble a crescent. At least one of the ends of the cell must be pointed. Generally, the membrane is smooth and the cell stains uniformly throughout. Sickle cells result from the gelation of polymerized deoxygenated Hb S. Polymerization of Hb S is influenced by both lowered oxygen levels and decreased blood pH. A variety of chemical factors contribute to membrane changes in these cells. The influx of sodium ions and other metabolic changes produce an extremely increased level of intracellular calcium ions. Alterations in the cellular contents produce cell membrane rigidity. The presence of sickle cells is associated with sickle cell anemia.
Spherocytes
Spherocytes are erythrocytes that have lost their normal biconcave shape. This type of cell has an extremely compact, round shape. It is usually smaller than 6 mm and has an intense orange-red color when stained. Spherocytelike erythrocytes may appear as artifacts if a slide is examined at the thin end of a normal blood smear. Spherocytes occur as the ratio of surface area of the erythrocyte to the volume of the cell contents decreases because of the loss of cell membrane. This loss of cell membrane creates membrane instability. Membrane instability and the decreased deformability of the spherical cells lead to premature cell destruction. Spherocytes may be formed because of an inherited structural defect of the erythrocyte membrane or from direct physical trauma such as heat or chemical injury. Clinical disorders associated with spherocytes include acquired hemolytic anemia, blood transfusion reactions, congenital spherocytosis, and DIC. Microspherocytes are associated with ABO hemolytic disease of the fetus and newborn and a storage phenomenon that produces microspherocytes in the recipient of a blood transfusion. Hereditary spherocytosis is a very heterogeneous form of hemolytic anemia.