on 11-Nov-2021 (Thu)

The serum iron level represents the amount of circulating iron bound to transfer- rin. The TIBC is an indirect measure of the circulating transferrin. The normal range for the serum iron is 50–150 μg/dL; the normal range for TIBC is 300–360 μg/dL. Transferrin saturation, which is normally 25–50%, is obtained by the following formula: serum iron × 100 ÷ TIBC. Iron-deficiency states are associated with saturation levels <0%. There is a diurnal variation in the serum iron. A transferrin saturation >50% indicates that a disproportionate amount of the iron bound to trans- ferrin is being delivered to nonerythroid tissues. If this persists for an extended time, tissue iron overload may occur.

ree iron is toxic to cells, and the body has estab- lished an elaborate set of protective mechanisms to bind iron in various tissue compartments. Within cells, iron is stored complexed to protein as ferritin or hemosiderin. Apoferritin binds to free ferrous iron and stores it in the ferric state. As ferritin accumulates within cells of the RE system, protein aggregates are formed as hemosiderin. Iron in ferritin or hemosiderin can be extracted for release by the RE cells, although hemosiderin is less readily available. Under steady-state conditions, the serum ferritin level correlates with total body iron stores; thus, the serum ferritin level is the most convenient laboratory test to estimate iron stores. The normal value for ferritin varies according to the age and gender of the individual (Fig. 93-3). Adult males have serum ferritin values averaging 100 μg/L, while adult females have levels averaging 30 μg/L. As iron stores are depleted, the serum ferritin falls to <es

The serum ferritin level is a better indicator of iron overload than the marrow iron stain. However, in addition to storage iron, the marrow iron stain provides information about the effective delivery of iron to developing erythroblasts.

In states in which release of iron from storage sites is blocked, RE iron will be detectable, and there will be few or no sideroblasts.

In the myelodysplastic syn- dromes, mitochondrial dysfunction can occur, and accumulation of iron in mitochondria appears in a necklace fashion around the nucleus of the erythroblast. Such cells are referred to as ring sideroblasts.

Protoporphyrin is an inter- mediate in the pathway to heme synthesis. Under conditions in which heme synthesis is impaired, protoporphyrin accumulates within the red cell. This reflects an inadequate iron supply to erythroid precursors to support hemoglobin synthesis. Normal values are <30 μg/dL="" of="" red="" cells.="" In="" iron="" deficiency,="" values="">100 μg/dL are seen. The most common causes of increased red cell protoporphyrin levels are absolute or rela- tive iron deficiency and lead poisoning.

Because erythroid cells have the highest numbers of transferrin receptors of any cell in the body, and because transferrin receptor protein (TRP) is released by cells into the circulation, serum levels of TRP reflect the total erythroid marrow mass. Another condition in which TRP levels are elevated is absolute iron deficiency. Normal values are 4–9 μg/L determined by immunoassay. This laboratory test is becoming increas- ingly available and, along with the serum ferritin, has been proposed to distinguish between iron deficiency and the anemia of inflammation

Other than iron deficiency, only three conditions need to be consid- ered in the differential diagnosis of a hypochromic microcytic anemia (Table 93-4). The first is an inherited defect in globin chain synthesis: the thalassemias. These are differentiated from iron deficiency most readily by serum iron values; normal or increased serum iron levels and transferrin saturation are characteristic of the thalassemias. In addition, the red blood cell distribution width (RDW) index is gener- ally normal in thalassemia and elevated in iron deficiency. The second condition is the anemia of inflammation (AI; also referred to as the anemia of chronic disease) with inadequate iron supply to the erythroid marrow. The distinction between true iron- deficiency anemia and AI is among the most common diagnostic prob- lems encountered by clinicians (see below). Usually, AI is normocytic and normochromic. The iron values usually make the differential diag- nosis clear, as the ferritin level is normal or increased and the percent transferrin saturation and TIBC are typically below normal. Finally, the myelodysplastic syndromes represent the third and least common condition. Occasionally, patients with myelodysplasia have impaired hemoglobin synthesis with mitochondrial dysfunction, resulting in impaired iron incorporation into heme. The iron values again reveal normal stores and more than an adequate supply to the marrow, despite the microcytosis and hypochromia. TREATMENT Iron-Deficiency Anemia The severity and cause of iron-deficiency anemia will determine the appropriate approach to treatment. As an example, symptom- atic elderly patients with severe iron-deficiency anemia and car- diovascular instability may require red cell transfusions. Younger individuals who have compensated for their anemia can be treated more conservatively with iron replacement. The foremost issue for the latter patient is the precise identification of the cause of the iron deficiency. For the majority of cases of iron deficiency (pregnant women, growing children and adolescents, patients with infrequent episodes of bleeding, and those with inadequate dietary intake of iron), oral iron therapy will suffice. For patients with unusual blood loss or malabsorption, specific diagnostic tests and appropriate therapy take priority. Once the diagnosis of iron-deficiency anemia and its cause is made, there are three major therapeutic approaches.