In a healthy adult, each of the 20 to 30 trillion red blood cells in the bloodstream contains more than 250 million molecules of hemoglobin. This vital, iron-containing protein transports oxygen to the body tissues. An abnormally low hemoglobin level results in anemia. Typical symptoms include fatigue and shortness of breath. If the anemia is mild or develops over a long period, noticeable symptoms may be mild or absent. But sudden or severe anemia can lead to heart failure and could be fatal. A low hemoglobin can result from decreased production or increased destruction of red blood cells, bone marrow problems and blood loss, among others.
Decreased production of red blood cells (RBCs) or the hemoglobin molecule itself, or both commonly leads to a low hemoglobin (HGB) level. Nutritional deficiencies are most frequently to blame, with iron deficiency the most likely culprit. Because iron is an essential component of the HGB molecule, insufficient intake leads to inadequate HGB and RBC production. A deficiency of vitamin B12, vitamin B6 and folate, or a combination of these nutritional deficiencies, also commonly leads to reduced HGB and RBC production.
HGB and RBC production occurs in the bone marrow. Therefore, bone marrow disorders can lead to a low hemoglobin. Aplastic anemia, for example, shuts down the bone marrow. This condition can occur due to radiation exposure, treatment with certain chemotherapy drugs and certain viral infections. In some cases, the cause of aplastic anemia is unknown. Other conditions that affect the bone marrow’s ability to produce RBCs include leukemia, lymphoma, multiple myeloma and other blood cancers. Certain hormonal disorders -- including reduced function of the thyroid, adrenal or pituitary gland -- and Inherited bone marrow disorders, such as Fanconi anemia and Diamond-Blackfan anemia, are can also cause reduced HGB related to decreased RBC production.
Increased RBC Destruction
RBCs typically circulate in the blood stream for approximately 3 month before being removed and replaced. Increased or premature RBC destruction can lead to decreased HGB and anemia if the bone marrow cannot compensate for the accelerated rate of loss. Hereditary hemoglobin disorders, such as sickle cell disease and thalassemia, are examples of this mechanism of anemia. With these conditions, the HGB molecules are abnormal, which causes the RBCs to be misshapen or inflexible. These abnormalities target them for early destruction. Other RBC abnormalities unrelated to the structure of the HGB molecule can also lead increased destruction. Examples include malaria, a parasitic infection of the RBCs, and hereditary spherocytosis, a genetic condition that affects the shape of the RBCs.
Autoimmune hemolytic anemia is another condition that leads to reduced HGB due to increased RBC destruction. With this condition, the immune system tags its own RBCs for destruction due to mistakenly identifying them as foreign. Reduced RBC survival might occur in people with a mechanical heart valve, which can damage the RBCs as they flow through the heart. People with a grossly enlarged spleen, which can occur with cirrhosis and other disorders, often experience a low HGB due to early removal of the RBCs from the circulation.
Anemia of Chronic Disease
Long-term medical conditions can adversely affect the interplay of the bone marrow and the rest of the body, leading to a condition called anemia of chronic disease. This condition is the second most common form of anemia worldwide, and occurs due to a combination of decreased RBC production and, in some cases, reduced RBC survival. Anemia of chronic disease most commonly occurs in people with chronic infections, such as hepatitis C and HIV/AIDS, or a long-term inflammatory condition, such as rheumatoid arthritis and systemic lupus erythematosus. However, the condition also occurs with noninfectious, noninflammatory chronic conditions, including cancer, diabetes, chronic kidney disease, heart failure, chronic obstructive pulmonary disease (COPD) and alcoholic liver disease.
Several mechanisms, alone or in combination, can contribute to anemia of chronic disease, including:
-- decreased production of the hormone erythropoietin (EPO), which stimulates the bone marrow to produce RBCs
-- blunted bone marrow response to EPO
-- sequestration of iron in immune system cells, making the mineral unavailable for HGB and RBC production
-- reduced RBC survival, for unknown causes
Anemia Due to Blood Loss
A low HGB can be due to sudden or slow, chronic blood loss. Sudden, massive blood loss typically occurs due to traumatic injury or a medical condition, such as a ruptured blood vessel or tubal pregnancy. Severe hemorrhaging can quickly lead to life-threatening anemia and shock that requires prompt blood transfusions and fluid replacement. Chronic blood loss is more common and can occur with a variety of medical conditions. Examples include heavy menstrual periods, internal hemorrhoids and diverticulitis. People with chronic blood loss typically develop an iron deficiency, but this is due to iron loss through bleeding rather than a nutritional deficiency.
Reviewed and revised by: Tina M. St. John, M.D.