Some of the relevant findings in peripheral blood, enlarged lymph nodes, and bone marrow are illustrated in this chapter. Systematic histologic examination of the bone marrow and lymph nodes is beyond the scope of a general medicine textbook. However, every internist should know how to examine a peripheral blood smear.
The examination of a peripheral blood smear is one of the most informative exercises a physician can perform. Although advances in automated technology have made the examination of a peripheral blood smear by a physician seem less important, the technology is not a completely satisfactory replacement for a blood smear interpretation by a trained medical professional who also knows the patient's clinical history, family history, social history, and physical findings. It is useful to ask the laboratory to generate a Wright's-stained peripheral blood smear and examine it.
The best place to examine blood cell morphology is the feathered edge of the blood smear where red cells lie in a single layer, side by side, just barely touching one another but not overlapping. The author's approach is to look at the smallest cellular elements, the platelets, first and work his way up in size to red cells and then white cells.
Using an oil immersion lens that magnifies the cells 100-fold, one counts the platelets in five to six fields, averages the number per field, and multiplies by 20,000 to get a rough estimate of the platelet count. The platelets are usually 1–2 μm in diameter and have a blue granulated appearance. There is usually 1 platelet for every 20 or so red cells. Of course, the automated counter is much more accurate, but gross disparities between the automated and manual counts should be assessed. Large platelets may be a sign of rapid platelet turnover, as young platelets are often larger than old ones; alternatively, certain rare inherited syndromes can produce large platelets. Platelet clumping visible on the smear can be associated with falsely low automated platelet counts. Similarly, neutrophil fragmentation can be a source of falsely elevated automated platelet counts.
Next one examines the red blood cells. One can gauge their size by comparing the red cell to the nucleus of a small lymphocyte. Both are normally about 8 μm wide. Red cells that are smaller than the small lymphocyte nucleus may be microcytic; those larger than the small lymphocyte nucleus may be macrocytic. Macrocytic cells also tend to be more oval than spherical in shape and are sometimes called macroovalocytes. The automated mean corpuscular volume (MCV) can assist in making a classification. However, some patients may have both iron and vitamin B12 deficiency, which will produce an MCV in the normal range but wide variation in red cell size. When the red cells vary greatly in size, anisocytosis is said to be present. When the red cells vary greatly in shape, poikilocytosis is said to be present. The electronic cell counter provides an independent assessment of variability in red cell size. It measures the range of red cell volumes and reports the results as "red cell distribution width" (RDW). This value is calculated from the MCV; thus, cell width is not being measured but cell volume is. The term is derived from the curve displaying the frequency of cells at each volume, also called the distribution. The width of red cell volume distribution curve is what determines the RDW. The RDW is calculated as follows: RDW = (standard deviation of MCV ÷ mean MCV) × 100. In the presence of morphologic anisocytosis, RDW (normally 11–14%) increases to 15–18%. The RDW is useful in at least two clinical settings. In patients with microcytic anemia, the differential diagnosis is generally between iron deficiency and thalassemia. In thalassemia, the small red cells are generally of uniform size with a normal small RDW. In iron deficiency, the size variability and the RDW are large. In addition, a large RDW can suggest a dimorphic anemia when a chronic atrophic gastritis can produce both vitamin B12 malabsorption to produce macrocytic anemia and blood loss to produce iron deficiency. In such settings, RDW is also large. An elevated RDW also has been reported as a risk factor for all-cause mortality in population-based studies (Patel KV et al: Arch Intern Med 169:515, 2009), a finding that is unexplained currently.
After red cell size is assessed, one examines the hemoglobin content of the cells. They are either normal in color (normochromic) or pale in color (hypochromic). They are never "hyperchromic." If more than the normal amount of hemoglobin is made, the cells get larger—they do not become darker. In addition to hemoglobin content, the red cells are examined for inclusions. Red cell inclusions are the following:
Basophilic stippling—diffuse fine or coarse blue dots in the red cell usually representing RNA residue—especially common in lead poisoning
Howell-Jolly bodies—dense blue circular inclusions that represent nuclear remnants—their presence implies defective splenic function
Nuclei—red cells may be released or pushed out of the marrow prematurely before nuclear extrusion—often implies a myelophthisic process or a vigorous narrow response to anemia, usually hemolytic anemia
Parasites—red cell parasites include malaria and babesia (Chap. e27)
Polychromatophilia—the red cell cytoplasm has a bluish hue, reflecting the persistence of ribosomes still actively making hemoglobin in a young red cell
Vital stains are necessary to see precipitated hemoglobin called Heinz bodies.
Red cells can take on a variety of different shapes. All abnormally shaped red cells are poikilocytes. Small red cells without the central pallor are spherocytes; they can be seen in hereditary spherocytosis, hemolytic anemias of other causes, and clostridial sepsis. Dacrocytes are teardrop-shaped cells that can be seen in hemolytic anemias, severe iron deficiency, thalassemias, myelofibrosis, and myelodysplastic syndromes. Schistocytes are helmet-shaped cells that reflect microangiopathic hemolytic anemia or fragmentation on an artificial ...