Chapter 12. Hematopathology

Hematopathology includes both diseases of red blood cells and diseases of white blood cells, as well as coagulation disorders. The first part of this chapter will discuss diseases of red blood cells, including general features of anemia, microcytic anemia, macrocytic anemia, and other anemias associated with decreased production, general features of hemolytic anemias, antibody-mediated destruction of red blood cells and other external causes of red blood cell destruction, hereditary causes of increased red blood cell destruction, and polycythemia. The second part of the chapter will discuss diseases of white blood cells and coagulation disorders.

Overview: A shortage of red blood cells is referred to as anemia. There are three mechanisms by which the body becomes anemic: blood loss (either acute or chronic), decreased production of red blood cells, and increased destruction of red blood cells (i.e., hemolysis). These anemias can be categorized in two general ways: by mechanism (as outlined above), and by morphology, such as by mean corpuscular volume (MCV). To evaluate an anemia, the initial step is classification based upon the MCV, the reticulocyte count, and the blood smear. A high reticulocyte count indicates that the bone marrow is responding to the anemia by producing red blood cells. A low reticulocyte count indicates a production problem. The laboratory measures red cell indices based upon the size of the red blood cell and the amount of hemoglobin (Hb) per cell. Of these, MCV is very important in the morphologic classification of anemias. The other red cell indices are mean cell hemoglobin (MCH), mean cell Hb concentration (MCHC), and red cell distribution width (RDW). Anemias due to a deficiency of a substance (e.g., iron) usually have a higher RDW than anemias due to a genetic defect or bone marrow disorder.

Mechanisms of anemia: Blood loss, decreased production of red blood cells, and increased destruction of red blood cells due to external factors and both hereditary and acquired internal factors (Table 12-1).

1. Causes of blood loss

   • Acute blood loss: Often due to trauma.
   • Chronic blood loss: Often due to bleeding from gastrointestinal malignancies or menstruation.

2. Causes of decreased production of red blood cells

   • Disturbance of stem cells (e.g., aplastic anemia, pure red cell aplasia).
   • Defective heme production (e.g., iron deficiency, thalassemias).
   • Defective DNA production (e.g., vitamin B12 and folate deficiencies).
   • Destruction of bone marrow (e.g., metastatic tumor).

3. Causes of increased destruction of red blood cells due to external factors

   • Antibody mediated: Etiology is either isohemagglutinin (e.g., transfusion reactions or erythroblastosis fetalis) or autoimmune.
   • Trauma to red cells.
   • Infectious (e.g., malaria).
   • Sequestration in an enlarged spleen.

4. Causes of increased destruction of red blood cells due to hereditary internal factors

   • Defects in cytoskeleton (e.g., hereditary spherocytosis).
   • Structurally abnormal hemoglobin (e.g., sickle cell anemia, thalassemias).
   • Enzyme deficiencies (e.g., glucose-6-phosphate dehydrogenase [G6PD] deficiency).

5. Cause of increased destruction due to acquired defect: Paroxysmal nocturnal hemoglobinuria (PNH)

   • Defect: In normal red blood cells, phosphatidylinositol glycan A (PIGA) is needed for synthesis ...