Investigation and classification of anemia

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CHAPTER 6 Investigation and classification of anemia

Clinical features of anemia

A detailed clinical history is critical in determining the cause of anemia. Table 6.2 lists some of the important personal, dietary, drug and family history issues to be explored. The symptoms and signs of anemia result from decreased tissue oxygenation leading to organ dysfunction as well as from adaptive changes, particularly in the cardiovascular system.1,2 The nature and severity of symptoms is influenced by:

Table 6.2 Clinical history in the investigation of anemia

History Mechanism Examples
Current illness Acute hemorrhage Epistaxis, menorrhagia, hematemesis, melaena
Chronic blood loss Menorrhagia, melaena
Infection Parvovirus
Hemolysis Jaundice
Past medical history Anemia of chronic disease Chronic infection
Liver disease
Renal impairment
Malabsorption Gastrectomy
Gastric bypass
Celiac disease
Ileal surgery
Travel history Intra-erythrocytic parasites Malaria
Dietary history Vegetarian or veganism Vitamin B12 deficiency
Iron intake Iron deficiency
Excess alcohol Liver disease
Drugs Antiplatelet agents Aspirin, clopidogrel
Anticoagulants Warfarin
Oxidant drugs Salazopyrin, dapsone
Myelosuppressive agents Methotrexate
Cytotoxic chemotherapy
Exposure to toxins Toxins or chemicals that interfere with erythropoiesis Lead, aluminum
Family history Inherited red cell abnormality Hereditary spherocytosis
G6PD deficiency
Other hemoglobinopathy
Autoimmune disorders Pernicious anemia
Rheumatoid arthritis
Bleeding disorders Hemophilia
von Willebrand disease

Symptoms of anemia include lassitude, easy fatigability, dyspnea on exertion, palpitations, angina and intermittent claudication, headache, vertigo, light-headedness, visual disturbances, drowsiness, anorexia, nausea, bowel disturbances, menstrual disturbances and loss of libido. Physical signs include pallor, signs of a hyperkinetic circulation (tachycardia, wide pulse pressure with capillary pulsation, cardiac murmurs), signs of congestive cardiac failure, and hemorrhages and exudates in the retina. Severe anemia may also cause slight proteinuria, mild impairment of renal function and low-grade fever.

A moderate degree of chronic anemia is usually associated with only mild symptoms accompanied by slight increases in cardiac output at rest and slight decreases in mixed venous PO2. This is because there is a substantial shift of the oxygen dissociation curve to the right (see Chapter 1), mainly due to an adaptive increase in the levels of red cell 2,3-diphosphoglycerate. When the hemoglobin falls below 7–8 g/dl symptoms usually become more marked. The intra-erythrocytic adaptation cannot by itself maintain adequate oxygen delivery to the tissues and other compensatory mechanisms come into effect. These include:

The blood count and red cell indices in anemia

The mean cell volume (MCV) is the most useful red cell parameter for the assessment of the underlying cause of anemia. By using the MCV, anemias can be categorized by red cell size as microcytic (MCV <80 fl), normocytic (normal MCV) or macrocytic (MCV >100 fl). This provides a practical and rapid way of assessing possible causes and guiding further investigations (see below and Table 6.3). The mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC) are generally of less value than the MCV in the assessment of anemia. The red cell distribution width (RDW), a quantitative measure of the degree of variation in red cell size, can be useful in the assessment of some types of anemia. Usually erythrocytes are of a standard size (6–8 µm) and the RDW is 12–14%. A high RDW indicates that there is variation in erythrocyte size and gives a quantitative measure of anisocytosis. For example, in microcytic anemias, a normal RDW is generally seen in thalassemias whereas in iron deficiency it is mildly elevated. The graphical depiction of red cell features on blood count histograms, such as red cell number versus MCV, may also give an indication of anisocytosis, or the presence of dimorphic populations of erythrocytes.

Table 6.3 Practical classification of anemia based on mean cell volume

Types Mean cell volume Conditions
Microcytic <80 fl Iron deficiency
Anemia of chronic disease
Hereditary sideroblastic anemia
Normocytic Within reference range
(80–100 fl)
Blood loss
Failure of erythropoiesis
Macrocytic >80 fl Deficiency of folate or vitamin B12
Liver disease

The reticulocyte count can be used as a guide to distinguish between reduced bone marrow erythropoiesis and accelerated red cell loss as the primary cause of the anemia. An inappropriately low reticulocyte count for the degree of anemia indicates that there is impaired marrow erythroid response to the anemia, i.e., the underlying cause is interfering with marrow erythropoiesis. This may be due to a chronic infective or inflammatory process, bone marrow failure or infiltration, reduced hematinics, ineffective erythropoiesis (dyserythropoiesis) or inadequate erythropoietin as occurs in renal failure. In contrast an appropriate reticulocytosis is evidence that the marrow is responding to the anemia and the cause is likely to be peripheral (i.e. hemolysis or blood loss). Other red blood cell measurements, such as the nucleated red cell count and immature reticulocyte fraction, do not generally add significant value to the investigation of anemia.

The leukocyte and platelet counts will distinguish isolated anemia from pancytopenia. Neutrophilia and/or thrombocytosis can be seen in response to acute blood loss and hemolysis. The presence of abnormal leukocytes in the presence of anemia (e.g. blast cells) may indicate underlying bone marrow failure as a result of a neoplastic infiltrate.