Hemoglobin

Hemoglobin (abbreviated Hgb or Hb) is the protein molecule in red blood cells that carries oxygen from the lungs to the body's tissues and returns carbon dioxide from the tissues back to the lungs.

Hgb is made up of four protein molecules (globulin chains) that are connected.

• The normal adult hemoglobin molecule contains two alpha-globulin chains and two beta-globulin chains.
• In fetuses and infants, beta chains are not common and the hemoglobin molecule is made up of two alpha chains and two gamma chains.
• As the infant grows, the gamma chains are gradually replaced by beta chains, forming the adult hemoglobin structure.

Each globulin chain contains an important iron-containing porphyrin compound termed heme. Embedded within the heme compound is an iron atom that is vital in transporting oxygen and carbon dioxide in our blood. The iron contained in hemoglobin is also responsible for the red color of blood.

It also plays an important role in maintaining the shape of the red blood cells. In their natural shape, red blood cells are round with narrow centers resembling a donut without a hole in the middle. Abnormal hemoglobin structure can, therefore, disrupt the shape of red blood cells and impede their function and flow through blood vessels.

Hemoglobin is usually measured as a part of the routine complete blood count (CBC) test from a blood sample. The hemoglobin level is expressed as the amount of hemoglobin in grams (gm) per deciliter (dL) of whole blood, a deciliter being 100 milliliters.

Several methods exist for measuring hemoglobin, most of which are done currently by automated machines designed to perform different tests on blood. Within the machine, the red blood cells are broken down to get the hemoglobin into a solution. The free hemoglobin is exposed to a chemical containing cyanide that binds tightly with the hemoglobin molecule to form cyanomethemoglobin. By shining a light through the solution and measuring how much light is absorbed (specifically at a wavelength of 540 nanometers), the amount of hemoglobin can be determined.

Normal hemoglobin levels depend on the age and, beginning in adolescence, the gender of the person. Hemoglobin normal range values are:

All of these values from a hemoglobin blood test may vary slightly between laboratories. Some laboratories do not differentiate between adult and "after middle age" hemoglobin values. Pregnant females are advised to avoid both high and low hemoglobin levels to avoid increased risks of stillbirths (high hemoglobin – above the hemoglobin normal range) and premature birth or low-birth-weight babies (low hemoglobin – below the hemoglobin normal range).

Low levels of hemoglobin indicate the presence of anemia, and the reason for the anemia should be determined. While values for hemoglobin in the normal range can vary slightly between different laboratories and instruments; in general, values lower than the normal levels indicated above warrant further medical investigation.

A low hemoglobin level is referred to as anemia or low red blood count. A lower-than-normal number of red blood cells is referred to as anemia and hemoglobin levels reflect this number. There are many reasons (causes) for anemia.

What causes low hemoglobin levels?

Some of the more common causes of anemia include:

• Loss of blood (traumatic injury, surgery, bleeding, colon cancer, or stomach ulcer)
• Nutritional deficiency (iron, vitamin B12, folate)
• Bone marrow problems (replacement of bone marrow by cancer)
• Suppression by red blood cell synthesis by chemotherapy drugs
• Kidney failure
• Abnormal hemoglobin structure (sickle cell anemia or thalassemia)

In inflammatory conditions including certain chronic diseases, there may be a normal or sometimes increased amount of iron in the body but a low level of hemoglobin in the blood. Inflammation may prevent the use of stored iron to make enough healthy red blood cells, leading to anemia.

This condition is referred to as anemia of inflammation or anemia of chronic disease (ACD). This type of anemia occurs in people who have conditions such as infections, autoimmune diseases, cancer, and chronic kidney disease (CKD). 

When you have anemia, either your body doesn’t have enough red blood cells or your red blood cells are not functioning well. If your red blood cells can’t get enough oxygen to the rest of your body, you may have symptoms such as:

• Fatigue: Even with mild anemia, you may feel very tired and weak. Fatigue is often one of the first symptoms of anemia.
• Pale skin and gums: Another early symptom of anemia is skin and gums that are paler than usual or yellowish.
• Temperature issues: As anemia worsens, it can cause increased sweating or cold hands and feet.
• Dizziness: Moderate anemia can make you feel dizzy (like the room is spinning) or lightheaded (like you might pass out).
• Rapid heart rate: Fewer red blood cells mean your heart has to pump harder than usual to get enough oxygen to all the parts of your body, so your pulse may be faster. Severe anemia can even cause an irregular heartbeat.
• Tinnitus: Someone with tinnitus hears sounds in their ears even when it is silent. When your heart has to work harder to get blood to your brain, you may hear the increased blood flow through your inner ear. Tinnitus is often described as “ringing in the ears,” but people with anemia may hear more of a pounding or whooshing sound.
• Headache: Moderate to severe anemia can cause frequent headaches. Like the other symptoms listed here, headaches have other causes and don’t necessarily mean you have anemia.
• Shortness of breath: Moderate anemia can make you breathe faster than normal. When anemia becomes severe, you may feel like you can’t catch your breath or experience chest pain.

Higher than normal hemoglobin levels can be seen in people living at high altitudes and in people who smoke. Dehydration produces a falsely high hemoglobin measurement that disappears when the proper fluid balance is restored.

What causes high hemoglobin levels?

Some other infrequent causes are high hemoglobin levels include:

• Advanced lung disease (for example, emphysema)
• Certain tumors
• A disorder of the bone marrow known as polycythemia rubra vera, and
• Abuse of the drug erythropoietin (Epogen) by athletes for blood doping purposes (increasing the amount of oxygen available to the body by chemically raising the production of red blood cells)

Picture of Sickle Cell Red Blood Cell and Healthy Red Blood Cells

Sickle cell disease is a genetic condition in which the quality of hemoglobin is defective. This condition can cause abnormal hemoglobin that can result in abnormally shaped (sickled) red blood cells (see illustration). These abnormal red blood cells cannot easily pass through small blood vessels leading to inadequate oxygen for the tissues of the body.

Sickle cells also have a shorter life span than normal red blood cells (10 to 20 days compared to 120 days). This rapid turnover may result in inadequate time to replace the red blood cells and may result in anemia.

In sickle cell anemia, one defective hemoglobin gene is inherited from each parent. If only one gene is inherited from one parent, then the condition is milder and referred to as sickle cell trait.

Symptoms of sickle cell anemia vary depending on its severity. Patients with sickle cell trait may experience mild if any, symptoms at all. In sickle cell disease, symptoms are more significant, especially in episodes of acute crisis. These symptoms can include:

• Generalized body aches and pain
• Chest pain
• Bone pain
• Shortness of breath
• Ulceration of the skin
• Fatigue
• Strokes
• Blindness
• Delayed growth and puberty

A thalassemia is a group of hereditary conditions with quantitative hemoglobin deficiency. The body's failure to make globulin molecules will lead to a compensatory mechanism to make other less compatible globulin molecules. The different types of thalassemia are defined based on what type of globulin molecule is deficient. The severity of these conditions depends on the type of deficient globulin chain, the number of deficient globulins, and the severity of the underproduction. Mild disease may only present as mild anemia whereas severe deficiency may not be compatible with life.

Hemoglobin A1c or glycosylated hemoglobin is a rough indication of blood sugar control in people with diabetes mellitus over the preceding 3 months. As more glucose (blood sugar) circulates in the blood daily, more glucose is bound to the circulating hemoglobin. Normal hemoglobin A1c levels range between 4% to 5.9%. As this number reaches 6% or greater, it signifies a higher than normal level of blood glucose over the preceding 3 months.

What does it mean when your hemoglobin A1C is high?

A hemoglobin A1c of 6% roughly correlates with an average blood sugar level of 135 mg/dL (milligrams per deciliters) over the previous 3 months. Each 1% increase in hemoglobin A1c above 6% represents an average blood sugar of approximately 35 mg/dL over 135 mg/dL. For example, a hemoglobin A1c measurement of 7% corresponds to an average blood sugar level of 170 mg/dL in the previous 3 months.

If you have diabetes, a high hemoglobin A1C means that you are more likely to experience complications including:

• Problems with eyesight
• Heart disease
• Stroke
• Kidney disease
• Nerve damage

The hemoglobin A1c measurement is also important in screening for diabetes. People with an A1C greater than 6% are at high risk of developing diabetes in the next 5 years. Identifying them is critical because research shows that two interventions can lower their chances of developing diabetes. Lifestyle changes can reduce the risk by 50%. Using the drug metformin can reduce it by 30%. 

There are several ways to increase hemoglobin levels in the treatment of anemia. In general, low levels that need to be increased are caused by three circumstances:

• Decreased red blood cell production (for example, altered bone marrow hemoglobin production, iron deficiency)
• Increased red blood cell destruction (for example, liver disease)
• By blood loss (for example, trauma from a gunshot or knife wound)

Addressing these underlying causes of low hemoglobin levels initially determines what method to use to increase hemoglobin levels.

How can I raise my hemoglobin level quickly?

Methods to increase hemoglobin levels are varied and their use depends on the underlying problems. Some of the ways to increase levels  include:

• Transfusing red blood cells, which is the fastest way to treat anemia but is reserved for severe cases
• Receiving erythropoietin (a hormone used to stimulate red blood cell production in individuals with decreased red blood cell production or increased red cell destruction)
• Taking iron supplements
• Increasing the intake of iron-rich foods (eggs, spinach, artichokes, beans, lean meats, and seafood) and foods rich in cofactors (such as vitamin B6, folic acid, vitamin B12, and vitamin C) is important for maintaining normal hemoglobin levels. Such foods include fish, vegetables, nuts, cereals, peas, and citrus fruits.

How quickly does IV iron increase hemoglobin?

Individuals should not take oral or receive intravenous (IV) iron supplements or other treatments for low hemoglobin levels without first discussing such treatments with their physician, as side effects from these treatments and/or excess iron intake may cause additional problems. Also, iron supplements should be kept away from children because iron poisoning in young children can be fatal. Intravenous iron supplementation can raise hemoglobin levels typically within a few weeks and are sometimes considered before surgery in people with iron deficiency anemia.

Certain foods can be consumed to increase iron intake to treat people with anemia, but abnormally high levels of hemoglobin (as seen in smokers and those living at high altitude as well as people with certain medical conditions) do not typically result from an iron-rich diet. In addition to iron-rich foods, foods that have high folate, vitamin B12, or vitamin B6 content may also help increase hemoglobin levels. Foods that contain vitamin A, vitamin C, or beta-carotene may help the body absorb iron better.

Food that may help increase hemoglobin levels include:

1. Iron-rich foods: Meat, fish, soy, eggs, dried fruits, broccoli, leafy greens, green beans, nuts, and seeds
2. Vitamin C-rich foods: Oranges, lemons, kiwi, strawberries, papaya, bell pepper, broccoli, grapefruit, tomato, black currant, Brussels sprouts, and potatoes
3. Folate-rich foods: Beef, leafy greens, rice, peanuts, black-eyed peas, kidney beans, avocados, sprouts, wheat germ, bananas, broccoli, and chicken liver
4. Apples and pomegranates
5. Brown rice
6. Dark chocolate
7. Nettle tea

Other tips to increase levels:

1. Avoid iron-blockers: Coffee, tea, cola drinks, wine, and beer
2. Take iron supplements

“POC” refers to “point of care.” A POC test is one that is done on a machine at the site of care that yields a rapid result, rather than sending the blood sample to a reference laboratory for measurement. If a healthcare team needs the results of a hemoglobin blood test right away, they will order a hemoglobin point-of-care (POC).