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Home , Cabot rings, Heinz body, Pappenheimer bodies, Poikilocytosis, Spherocytosis

HAEMATOLOGY

ABNORMAL RED CELL MORPHOLOGY MR. SAFARI • There are 4 main causes in which the abnormalities of red blood cells may arise pathologically. These are: 1. Abnormal erythropoeisis which will result in increase in size and shape . and . 2. Inadequate Hb formation which will result into reduced or unequal Hb content ( hypochromasia and anisochromasia) 3. Damage to or changes affecting the red cells after leaving the bone marrow which will result in 4. Attempts by the bone marrow to compensate for anaemia by increased erythropoiesis which will result into signs of immaturity (Polychromasia). Abnormalities in size of red blood cells (anisocytosis)

• This refers to increased variation in size of red blood cells. • This may be due to the presence of blood cells larger than normal (macrocytes)or cells smaller than normal (microcytes) or presence of both. • Frequently both microcytes and macrocytes are present together. • They are reported on the film depending on the ones which are in excess. For example; If the small cells are more than normal cells there is marked anisocytosis with microcytes. If the larger are more than the small ones there is marked anisocytosis with macrocytes. Macrocytes • Larger than normal • Have their MCD > 9 µm • They are found in megaloblastic anaemia, sometimes in aplastic anaemia and liver disease and whenever there is increased erythropoeisis. Microcytes • They are smaller than normal and their outline may be round or slightly irregular • They can be either hypochromic or normochromic • They are present in most of the anaemia and mainly evident in anaemia characterized by defective haemoglobinization especially in iron deficiency anaemia and some haemolytic anaemia. Abnormalities in shape of red blood cells ( POIKILOCYTOSIS)

• This refers to the increased variation in shape of red blood cells . • Poikilocytosis are produced in many types of abnormal erythropoiesis as in megaloblastic anaemia, iron deficiency anaemias, thalassaemia etc. • They may also be due to damage of circulating cells (rbcs) as in cases of micro-angiopathy. • Poikilocytosis are grouped into two forms or two cells: Cells with smooth margins e.g. spherocytes, target cells, and . Cells with irregular margins e.g. sickle cells ,tear drops cells, burr cells and creanated cells. Stomatocytes • These are red blood cells whose central bi- concave area appears oval, rectangular, elongated or slit like. • In wet preparation they appear cup shaped (cupped). Their presence in large number has been attributed to alcoholism or a genetic factor commonly in Australia. Burr cells (ecchinocytes/crenated cells) • Are creanated red cells • Small cells bearing one or a few fine spines. • They are probably damaged as fragmented cells which have undergone a type of crenation . • Their presence might indicate a haemolytic process. Projections are much smaller and more sharp than . • They have been noted in the blood in uremic carcinoma of the stomach and bleeding peptic ulcers. Elliptocytes ( Ovalocytes) • Are oval , normochromic cells (normal Hb) or elliptical shaped cells present in megaloblastic anaemia. • The cells may be inherited or acquired abnormally. • In inherited condition they will appear at reticulocyte stage but not in other normoblastic stages . • This defect is in red cell membrane . • They would also be associated with disorders of haemoglobin synthesis e.g. in thalassaemia, sickle cell anaemia, Hb C disease. Depranocytes (sickle cells) • They are crescent – moon shaped because of presence of Hb S • The cells are present in individuals with Hb SS, or Hb AS. • Can also appear when Hb SS is accompanied by other abnormal Hb’s e.g. Hb C, Hb D, etc. • When oxygenated they are normal in shape and when deoxygenated they sickle due to intracellular crystals formation( the red blood cells produce abnormal pigment (haemoglobin). The abnormal haemoglobin causes deformity of the red blood cells into crescent or sickle-shapes.) Creanated cells () • These are red cells showing numerous projections from their surface. • This creanation may be due to subjecting RBCs to hypotonic solutions, standing blood overnight at room temperature or the presence of fatty substances on the slides where films are made (greasy slides). Acanthocytes. • These are red blood cells associated with abnormal metabolism of phospholipids which is inherited. • Acanthocytes have prominent, irregularly shaped, blunt, finger-like projections seen in anaemia, chronic liver disease and post .  Creanated cells have fine projections which are regularly spaced while Acanthocytes have rough projections and irregularly spaced. Target cells • Are abnormally thin RBCs which stains at the centre and periphery , with an unstained ring in between. • Stained areas represent areas of haemoglobinization. This distribution of haemoglobin in the cell is only seen in stained films. • Are commonly seen in certain haemoglobinopathies e.g. Hb C disease, Hb S etc. • They also appear in haemolytic anaemia, liver cirrhosis and splenectomy (removal of ). spherocytes • They may be associated with a mild anaemia. Typically, the affected RBCs are small, spherically shaped, and lack the hollow centres seen in normal, round RBCs. Tear drop cells • Are Rbc's shaped like tears dropping from the eyes. • Are commonly found in haemolytic anaemias. Abnormalities in staining • These can be due to inadequate haemoglobin content (hypochromasia) or due to unequal haemoglobin content (anisochromasia) or due to signs of immaturity (polychromasia). The cells which fall under this group are: a. Hypochromic red blood cells (hypochromasia) b. Target cells (anisochromasia) c. Spherocytes (hyperchromasia), increase in the ratio of the weight of haemoglobin to the volume of the . d. Stomatocytes (hypochromasia) Hypochromic red blood cells • Paler cells than normal with a peripheral pink ring or a red blood cell with a central pallor. • The size and shape of the cells are variable. • The hypochromasia is due to defective haemoglobinization. • The degree of pallor depends on the extent to which the haemoglobin within the cell is reduced. • A normal red blood cell will have an area of pallor in the center of it; in hypochromic cells, this area of central pallor is increased. • This decrease in redness is due to a disproportionate reduction of red cell (the pigment that imparts the red color) in proportion to the volume of the cell. • Most common cause is iron deficiency and thalassemia. Factors responsible for production of hypochromasia. 1. Absent iron store (iron deficiency) 2. Normal iron storage with defective mobilization of iron from body store to the required site of erythropoiesis. 3. Impaired protoporphyrin and haem synthesis (haemopathy) 4. Abnormal globin chain synthesis (globinopathy) Red blood cell inclusions • These are intracellular particles which are found in red blood cells in abnormal conditions and they are not supposed to be there. Examples are; Howell jolly bodies Heinz bodies  Reticulum fibres  Howell jolly bodies • These are small, round, purple or dark violet particles situated at the centre or very close to the centre of RBC. • They are histopathological findings of basophilic nuclear remnants (clusters of DNA) in circulating erythrocytes. • During maturation in the bone marrow erythrocytes normally expel their nuclei, but in some cases a small portion of DNA remains. • The RBC in the centre of the field contains several Howell-Jolly bodies, or inclusions of nuclear chromatin remnants. There is also a nucleated RBC just beneath this RBC. Abnormal and aged RBC's are typically removed by the spleen. The appearance of increased poikilocytosis, anisocytosis, and RBC inclusions suggests that a spleen is not present. Causes • Splenectomised patient. • Radiation therapy involving the spleen, such as that used to treat Hodgkin lymphoma. • Howell-Jolly bodies are also seen in: severe hemolytic , , , and (MDS). Heinz bodies • Heinz bodies appear as small round inclusions within the red cell body, though when stained with Romanowsky dyes they may appear as projections from the cell. • They appear more clearly when supravitally stained (e.g., with New methylene blue) • Heinz bodies are formed by damage to the hemoglobin component molecules, usually through oxidations, or the change of an internal amino acid residue(from an inherited mutation), Which causes an electron from the hemoglobin to be transferred to an molecule, which creates a Reactive Oxygen Species (ROS). • This can cause severe cell damage leading to premature cell lysis. • Damaged cells are cleared by in the spleen, where the precipitate and damaged membrane are removed, leading to characteristic "Bite cells".

• The denaturing process is irreversible and the continual elimination of damaged cells leads to anemia. • There are several pathways leading to the hemoglobin damage. • NADPH deficiency can cause a dysfunction in glutathione peroxidase which is an enzyme that converts (Reactive Oxygen Species) into water. • G6PD (Glucose-6-Phosphate Dehydrogenase) deficiency exacerbated by administration of oxidant drugs (e.g., primaquine, dapsone, quinidine) can also result in Heinz bodies. • Heinz bodies can also be found in chronic liver disease. • A degmacyte (aka "bite cell") is an abnormally shaped red blood cell with one or more semicircular portions removed from the cell margin.[These "bites" result from the removal of denatured hemoglobin by macrophages in the spleen. • Glucose-6-phosphate dehydrogenase deficiency, in which uncontrolled oxidative stress causes hemoglobin to denature and form Heinz bodies, is a common disorder that leads to the formation of bite cells. Basophilic stippling • Refers to an observation found when observing a blood smear, where erythrocytes display small dots at the periphery. These dots represent accumulations of RNA and are always pathological. • The dots are dark blue in Romanowsky stains and appear as purplish blue. It is associated with several conditions, including:  (Microcytic anemia) that is encountered in drug or chemical poisoning. • They suggests a toxic injury to the bone marrow, such as with lead poisoning. Such stippling may also appear with severe anaemia, such as a megaloblastic anaemia.

Pappenheimer bodies ( Siderocytes) • are abnormal granules of iron found inside red blood cells on routine blood stain. (are aggregates of ferric iron that has not been used in haem synthesis in precursor cells, thus resulting to cells containing granules of more haem iron.) • a small number present in normal blood

• They are a type of inclusion body formed by phagosomes that have engulfed excessive amounts of iron. • They appear as dense, blue-purple granules within the red blood cell and they are usually only one or two, located in the cell periphery.

• They are seen in diseases such as sideroblastic anemia, , and .

• They can interfere with platelet counts when the analysis is performed by electro-optical counters. • Pappenheimer bodies are visible with a Wright and/or . Confirmation of non- haem iron in the granules is made with a Prussian Blue stain. Reticulum fibres • Are young (juvenile) rbc nuclear remnants . • They are stained by supravital stains. • The appear as deep blue mesh of fibres . • They are increased in cases of blood loss e.g. haemoglobinopathies, sickle cell anaemia and haemolytic anaemia. • In stained preparations, polychromatophilic cells are seen. • Reticulocyte counts is very high. Cabot rings • Are thin, red-violet staining, threadlike strands in the shape of a loop or figure-8 that are found on rare occasions in erythrocytes. • They are believed to be microtubules that are remnants from a mitotic spindle.

• Cabot rings have been observed in a handful of cases in patients with megaloblastic anemia, lead poisoning and other disorders of erythropoeisis.