| Three RBC measurements are routinely carried out: packed cell volume (PCV), the proportion of whole blood volume occupied by RBC; hemoglobin (Hgb) concentration of whole lysed blood; and RBC count, the number of RBC per unit volume of whole blood. Although these are separate estimations, they are in effect 3 ways of measuring the
same thing, and it is incorrect to attempt to interpret them as separate variables. Inasmuch as they do vary in relation to each other, they allow calculation of 2 further meaningful parameters, mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC), as follows:
|
| MCV varies widely between mammalian species, from ~15 fL in goats to ~90 fL in humans. Avian and reptilian red cells are even larger, up to 300 fL. Nevertheless, MCHC varies little with species (or erythrocyte size), at ~33 g/dL. |
| Several artifacts can cause significant and potentially misleading alterations to measured erythrocyte parameters: 1) old samples cause RBC to swell, thus increasing PCV and MCV and decreasing MCHC; 2) lipemia causes a falsely high Hgb reading, and hence a falsely high MCHC; 3) hemolysis causes PCV to decrease while Hgb remains unchanged, again leading to a falsely high MCHC; 4) underfilling of the tube causes RBC to shrink, causing PCV and MCV to decrease and MCHC to increase; 5)
autoagglutination causes a falsely low RBC count, and hence a falsely high MCV. |
|
Visual description of RBC morphology on a Romanowsky stain also provides useful diagnostic information. The most common terms employed include: 1) Normocytic—cells are of normal size. 2) Macrocyte—abnormally large cell, usually polychromatophilic (see below). 3) Microcyte—abnormally small cell, usually
caused by a lack of hemoglobin precursors. 4) Anisocytosis—variation in size of cells, due to macrocytes, microcytes, or both. 5) Normochromic—cells are of normal color. 6) Polychromasia—variation in color of the cells. This usually describes the appearance of large, juvenile, bluish-staining polychromatophilic macrocytes. These broadly correspond to
the “reticulocyte” seen with new methylene blue staining, in which the reticulum represents the remnants of the nucleus. 7) Hypochromasia—decrease in staining density of the cells, usually due to a lack of hemoglobin precursors, especially iron. 8) Annulocyte—extreme form of hypochromic cell with only a thin rim of hemoglobin. |
| PCV is the variable normally used to assess the basic status of the erythron—increased in polycythemia, decreased in anemia—although if a sample is too hemolyzed to allow measurement of PCV, a meaningful Hgb measurement may still be obtained. RBC count as such should not be interpreted clinically. |
| An abnormally high PCV (polycythemia) may be relative, due to a change in the proportion of circulating RBC to blood plasma without any alteration in the size of the erythron, or absolute, due to a real increase in erythron size. Absolute polycythemia may be primary (eg, polycythemia vera or, rarely, erythropoietin-producing tumors) or secondary (a consequence of disease in another organ system). (See also
polycythemia,
Polycythemia: Introduction.) |
| Polycythemia vera and erythropoietin-producing tumors should only be suspected when PCV is very high, normally >0.70. The former is characterized by normal adult erythrocytes and a normal (or low) erythropoietin concentration, while the latter may show a regenerative RBC picture with high erythropoietin concentration. Relative polycythemia may also be associated with very high PCV values, and normal adult RBC. Secondary polycythemia generally shows a more modest increase in PCV,
often with evidence of regeneration (more so when the cause is pulmonary or cardiac, less so when the cause is hormonal). It is often possible to make the differential diagnosis of polycythemia on clinical grounds. |
| Abnormally low PCV (anemia) may be caused by loss of blood (hemorrhage), breakdown of erythrocytes in circulation (hemolysis), or lack of production of erythrocytes by the bone marrow (hypoplasia or aplasia). Presentation varies according to whether the condition is acute or chronic. Aplastic anemia is always chronic in onset because anemia occurs gradually as existing cells reach the end of their lifespan. (See also
anemia,
Anemia: Introduction.) |
| In acute hemorrhagic anemia, external blood loss is easily appreciated clinically, but blood loss into a body cavity may only be determined on paracentesis. Initially, all hematologic parameters may be normal, as it may take 12 hr for fluid shifts to produce a decrease in the PCV. Within a few days, RBC become regenerative, with juvenile forms appearing in circulation (except in horses, where circulating evidence of
regeneration is not readily appreciable). These consist of polychromatophilic macrocytes and normoblasts (nucleated RBC). Late normoblasts have a small, nonviable nucleus and a moderate amount of cytoplasm colored similarly to that of the polychromatophilic macrocytes, while early normoblasts have a larger, viable nucleus and scanty cytoplasm. These are most easily distinguished from lymphocytes by their more densely-staining nucleus. If substantial amounts of blood have been lost
from the body, the RBC picture may become hypochromic. Thus, this type of anemia shows an increase in MCV and a decrease in MCHC. If bleeding is into a body cavity, hypochromasia may not be evident because hemoglobin precursors will be recycled. However, slight jaundice may be seen as the sequestered cells are broken down. Some sequestered cells may also be returned to the circulation intact, if somewhat misshapen. |
| In acute hemolytic anemia, PCV will decrease immediately, and in the early stages some jaundice will be evident. In the very early stages, even a sample collected with extreme care may be markedly hemolyzed. As with hemorrhagic anemia, the RBC will become regenerative within a few days, with polychromatophilic macrocytes and nucleated RBC evident. However, as hemoglobin precursors are not lost from the body, true
hypochromasia is not seen. |
|
Chronic hemorrhagic anemia may be difficult to appreciate if blood is lost in the feces or urine, or due to bloodsucking ectoparasites. Anemia may be severe, and the RBC picture will be regenerative on presentation. Hypochromasia is usually very marked. In very longstanding conditions, depletion of iron and other hemoglobin precursors can become so marked that most of the cells are microcytic, and MCV may paradoxically
decrease. Intermittent intra-abdominal hemorrhage leads to a somewhat different picture, as blood shed into the peritoneal cavity can be returned to the circulation. PCV may therefore recover quickly, until the next episode, and signs of depletion of hemoglobin constituents do not emerge. |
| In chronic hemolytic anemia, RBC are regenerative on presentation, except that some cases of autoimmune hemolytic anemia (AIHA) paradoxically show little or no regeneration until treatment has been initiated. Hypochromasia is less marked than in hemorrhagic conditions, and misshapen erythrocytes (including target cells and folded cells) are more common. The
spherocyte, in which the erythrocyte loses its classic biconcave shape, is essentially pathognomonic for AIHA. Jaundice may be absent, because the products of the destruction of the erythrocytes may be cleared by the reticuloendothelial system and the liver as quickly as they are formed. |
|
Hypoplastic and aplastic anemia may be mild if RBC production is merely depressed secondary to some other disease. Protein, mineral, or vitamin deficiencies may cause hypoplastic anemia, but these are more likely to be secondary to another disease (eg, chronic hemorrhage or malabsorption) than simple dietary deficiency. Other diseases may cause depression of erythropoietin production, eg, renal failure, deficiencies of hormones that
usually stimulate erythropoietin production (eg, hypothyroidism, Addison’s disease), and chronic, debilitating conditions such as chronic infections, chronic parasitism, and neoplasia. RBC morphology is nonregenerative and may be hypochromic if a deficiency state is involved. Paradoxically, vitamin B12 and/or folic acid deficiency produces a macrocytic RBC picture due to early maturation arrest of the erythrocytes. Neoplasia of the bone marrow may cause severe
anemia as erythropoietic elements are crowded out, but some regeneration may be observed as the remaining bone marrow attempts to compensate. In this case, other bone marrow cell lines will also be affected. |
| True aplastic anemia refers to a failure of the entire bone marrow. The shorter-lived granulocytes and platelets decrease first, followed by a progressively severe anemia that is normocytic and normochromic. |
;)
;)
;)