Anemia

Anemia may mean two things (or both):

• A decreased level of Hb (hemoglobin) in the blood, in absolute numbers. This may be because the level of Hb in the red blood cells is low, or because the level of red blood cells (which contain all the Hb in the blood) is low (as in hemolysis).
• A decreased capacity of each Hb molecule to bind oxygen, due to a deformity, nitrate exposure, or due to competitive gasses, such as carbon monoxide (from smoking, car exhaust or incomplete combustion), for example.

Hemoglobin

Hemoglobin (Hb) is an iron-containing protein in the blood. Hb transports oxygen (and some other (competitive) gasses, such as CO₂ and nitric oxide) to all your organs. Organs need oxygen to make use of nutrients (including energy) through oxidation. A lower level of Hb may therefore lead to a (relative) lack of oxygen in various organs (hypoxia).

Low Hb level

There are multiple possible causes (and in various combinations) for a low Hb level.

• Low serum iron (most commonly); if there is too little iron available, too little new Hb molecules are produced (as Hb contains iron).
• Vitamin B6 deficiency
• Mutations in one or more Hb genes, as in Thalassemia, sickle cell disease and hemolytic anemia.
• Blood loss
• Bone marrow issues
• Chemotherapy
• Lead poisoning
• Kidney failure

Low serum iron

Low serum iron may be the result of depleted iron (ferritin) stores (iron deficiency), but may also be a deliberate tactic of the body, or the result of a genetic trait (which may come with an iron overload in organs, as in β-thalassemia). All these causes may result in various types of anemia.

• Iron deficiency anemia. This term may be misleading, as anemia combined with low serum iron may not necessarily be "iron deficiency anemia". Iron deficiency anemia is caused by too low levels of iron in the diet, or by the incapacity of the intestines to take up sufficient iron from the ingested food (which may be caused by dietary factors, or drugs). Good sources of iron are egg yolks, red meat and fish.
• 'Voluntary low serum iron'. Various bacteria need iron to multiply. Lowering serum iron is a weapon in fighting bacterial infections.
• β-thalassemia may come with low, normal or high serum iron levels, and elevated ferritin (iron stores in cells).
• Chronic inflammatory conditions may elevate ferritin levels (iron stores in cells). As a result, chronic inflammatory diseases may be characterized by both low serum iron and normal ferritin levels.

Thalassemia

Thalassemia is usually characterized by lower Hb and red blood cell levels. This is relatively protective against Malaria, as malaria merozoites (parasites) need to multiply in, and infect new red blood cells. As a result (of this heterozygous advantage), thalassemia is particularly present in (formerly) malaria-prone regions. In Thalassemia the production (of ineffective-) and destruction of red blood cells is elevated (freeing up iron) and also gastrointestinal iron absorption is increased. This leads to the accumulation of iron in various organs, which may eventually cause liver cirrhosis or -fibrosis, heart failure, growth impairment, diabetes and osteoporosis. Yet, the blood iron level may be low (or normal, or high) in Thalassemia. The severity of this disease depends on the nature of the mutation that causes it. Supplemental iron may have severe adverse effects. Besides ferritin leves, in Thalassemia the level of Hb F may be elevated, and various red blood cell abnormalities may occur (small, low Hb relative to surface, pale, cells of unequal size, abnormally shaped, fragmented).

There are various types of thalassemia, depending on what genes are affected. Particularly β-thalassemia can be misdiagnosed as (the more common) iron deficiency anemia, due to similar characteristics (both Hb and serum iron may be low).