Sickle cell disease (SCD) is a genetic disorder that causes red blood cells to take the shape of a sickle or a letter “C.” Levels of hemoglobin, a protein that helps carry oxygen on red blood cells, are also typically low.

Red blood cells are typically round. When a person has SCD, abnormal types of hemoglobin cause their red blood cells to change shape. This change makes it harder for red blood cells to move through the body and carry oxygen throughout the body. Reduced oxygen and blood flow to vital organs, such as the kidneys, can cause pain and even life threatening illnesses.

Low hemoglobin is common in people with SCD and can cause anemia. Sickle cell anemia is a form of SCD.

Read on to learn more about how sickle cell anemia can affect the structure and levels of hemoglobin, as well as how doctors might diagnose and treat this disease.

Hemoglobin levels in people with SCD are typically in the range of 6–11 grams per deciliter (g/dL), whereas they are around 12 mg/dL in people without SCD.

Lower hemoglobin levels can make it more difficult for red blood cells to carry oxygen throughout the body. This can cause a wide range of symptoms, including pain and exhaustion. Over time, SCD may affect most organs, including the eyes, kidneys, and liver.

In addition to causing low hemoglobin levels, SCD changes the hemoglobin, causing cells to sickle. These cells die early.

Sickled cells are also more likely to stick together, which can increase the risk of dangerous blood clots and pulmonary embolism.

Does sickle cell trait affect hemoglobin levels?

When a person has sickle cell trait, it means that they carry one gene for SCD, not two. Sickle cell trait is usually a benign condition that does not affect health or hemoglobin levels.

Because people with sickle cell trait have only one gene that affects hemoglobin, they usually have enough normal hemoglobin to prevent them from developing symptoms.

Can physical activity affect hemoglobin levels?

When a person experiences intense physical stress — such as when they are in a high altitude location or when an untrained person works out with great intensity — some of their red blood cells may sickle.

As a result, a person may develop a life threatening complication called rhabdomyolysis, which damages muscles, causing them to break down and release harmful substances into the blood.

In sickle cell anemia, the hemoglobin protein is not normal. A genetic mutation within the HBB gene causes the hemoglobin to contain a chemical called valine instead of glutamic acid in protein chains that form hemoglobin. This damages red blood cells, causing them to sickle and die sooner than usual.

The HBB gene is responsible for forming beta-globin chains, which are a component of hemoglobin.

The premature death of red blood cells can mean that both hemoglobin and red blood cell levels are chronically low. So, in addition to having blood cells that stick together and carry oxygen less effectively, a person will not have enough red blood cells to effectively transport oxygen.

Changes in hemoglobin structure

Hemoglobin consists of four protein subunits: two subunits of alpha-globin and two of beta-globin.

In people with SCD, certain mutations within the HBB gene can change the structure of the hemoglobin. Specifically, mutations code for an abnormal version of beta-globin, or HbS. This might occur in only one of the two beta-globin subunits.

However, in sickle cell anemia, both beta-globin subunits of hemoglobin are replaced by abnormal HbS. This leads to the distortion of red blood cells and causes them to adopt a sickle shape.

In other types of SCD, the hemoglobin subunits may be replaced with other abnormal hemoglobin types, such as HbC. These can also change the shape of the red blood cells.

The type of SCD a person has will influence the symptoms they experience. The genes a person inherits determine the type of SCD they develop.

The most common types of SCD are:

  • Homozygous hemoglobin SS: The most common form of SCD, this variant means that a person inherits two copies of the “S” sickling gene — one from each parent. This is the most severe manifestation of SCD. Doctors call it sickle cell anemia.
  • Hemoglobin sickle cell disease: People with this milder type of SCD inherit one “S” sickling gene and one “C” sickling gene, which is another type of abnormal hemoglobin gene.
  • Hemoglobin sickle cell beta-thalassemia: This version of SCD means that a person gets one “S” sickling protein and one gene for beta-thalassemia, which is another type of abnormal hemoglobin. There are two subtypes: beta0-thalassemia, which is a more severe form, and beta+-thalassemia, which tends to be milder.

People with access to medical care usually get a diagnosis as newborns. The routine newborn screening in the United States looks for signs of hemoglobin anomalies using a drop of blood. This screening can help medical professionals diagnose SCD.

If a person did not have a newborn screening test or does not live in a country that provides this type of screening, they can undergo blood tests as an adult to detect SCD.

Quantifying hemoglobin

Some laboratory tests can separate the hemoglobin to look for the different variants and quantify them from blood samples. These tests include:

  • Hemoglobin electrophoresis: This technique can identify the different hemoglobin types.
  • High performance liquid chromatography: This technique also detects most hemoglobin types.
  • Isoelectric focusing: This is a very sensitive method of detection.

Although hematopoietic stem cell transplants show potential as a cure for SCD, they are not widely available. No cure is available to most people, which means that treatment mostly focuses on managing symptoms.

A doctor may recommend lifestyle management strategies to prevent some complications associated with the condition. These strategies may include:

  • drinking plenty of water
  • washing one’s hands often to reduce the risk of infection
  • avoiding high altitudes

Pain-relieving medication can help people with SCD manage episodes of pain, or pain crises. During a sickle cell crisis, a person may need to stay in the hospital. If their red blood cell and hemoglobin counts get very low, a person may need a blood transfusion.

It is important for people with SCD to stay up to date with vaccinations and to practice safe food handling because they have a higher risk of serious complications if they contract an infection.

SCD can cause numerous complications and may shorten a person’s life, especially if they do not have access to adequate medical care. Possible complications include:

In sickle cell anemia, a person’s hemoglobin levels are chronically low. This can cause several complications. However, the severity of complications varies from person to person and depends heavily on the type of SCD a person has.

It is important for all people with SCD to get quality medical care, maintain a healthy lifestyle, and know the signs of an emergency so they can seek prompt care when necessary.