Sickle Cell Disease: Understanding Your Pathology Report

Section Editor: Kamran Mirza MD PhD
July 5, 2026

Sickle cell disease is an inherited blood disorder that changes the shape and function of red blood cells. It is caused by a change in the gene that makes hemoglobin, the protein inside red blood cells that carries oxygen. People with sickle cell disease make an abnormal form of hemoglobin called hemoglobin S (HbS). When oxygen levels are low, hemoglobin S causes red blood cells to become stiff and curved, like a crescent or sickle. These sickled cells break down early, leading to a shortage of red blood cells (anemia), and they can block small blood vessels, causing pain and organ damage. Sickle cell disease is usually identified through blood tests that examine the different types of hemoglobin.

This article will help you understand the blood test and hemoglobin analysis results used to diagnose sickle cell disease, what each term means, and why it matters for your care.

What causes sickle cell disease?

Sickle cell disease is caused by a change (mutation) in the HBB gene, which provides the instructions for making part of the hemoglobin protein. This change leads the body to produce hemoglobin S instead of the usual adult hemoglobin (hemoglobin A). Sickle cell disease is inherited, which means it is passed down from parents to children. A person must inherit two abnormal hemoglobin genes, one from each parent, to have the disease. The exact type of sickle cell disease depends on the combination of genes inherited:

Hemoglobin SS (sickle cell anemia) — Two hemoglobin S genes. This is the most common and usually the most severe form.
Hemoglobin SC — One hemoglobin S gene and one hemoglobin C gene.
Hemoglobin S/beta-thalassemia — One hemoglobin S gene combined with a beta-thalassemia gene, which can be more or less severe depending on the type.

A person who inherits only one hemoglobin S gene, along with one normal gene, has sickle cell trait rather than sickle cell disease. This distinction is explained later in the article.

What are the symptoms of sickle cell disease?

The symptoms of sickle cell disease come from the breakdown of red blood cells and the blocking of small blood vessels by sickled cells. Common problems include ongoing anemia with fatigue and shortness of breath, episodes of severe pain called pain crises, and a higher risk of infections because the spleen is often damaged over time. Blocked blood vessels can also affect many organs, leading to complications involving the lungs, brain, kidneys, bones, and eyes. The severity varies widely from person to person, even among people with the same type of sickle cell disease.

How is the diagnosis made?

Sickle cell disease is diagnosed with blood tests, and in many countries it is first identified through newborn screening shortly after birth. The most important test is hemoglobin analysis, which separates and measures the different types of hemoglobin in the blood. This can be done using several laboratory methods, including hemoglobin electrophoresis, high-performance liquid chromatography (HPLC), and capillary electrophoresis. These methods all work by separating the hemoglobins so that each type can be identified and measured, and the results are reported as the percentage of each hemoglobin present.

A complete blood count (CBC) and a blood smear (a thin layer of blood examined under the microscope) are also part of the workup, and a simple screening test called the sickle solubility test may be used to detect whether hemoglobin S is present. The sickle solubility test can confirm that hemoglobin S is present, but it cannot measure how much is there or tell the difference between sickle cell disease and sickle cell trait, so it is always followed by hemoglobin analysis. In some cases, genetic testing of the HBB gene is performed to confirm the exact type of sickle cell disease, particularly when hemoglobin analysis cannot clearly separate two similar conditions, or for family planning and carrier testing.

What do the hemoglobin analysis and blood smear show?

The hemoglobin analysis report lists the different hemoglobins found in the blood and the percentage of each. In a healthy adult, most of the hemoglobin is hemoglobin A, with small amounts of hemoglobin A2 and hemoglobin F (fetal hemoglobin). In sickle cell disease, the pattern is different depending on the type:

Hemoglobin SS (sickle cell anemia) — Most of the hemoglobin is hemoglobin S, with little or no hemoglobin A, and a variable amount of hemoglobin F.
Hemoglobin SC — Roughly equal amounts of hemoglobin S and hemoglobin C, with no hemoglobin A.
Hemoglobin S/beta-thalassemia — Mostly hemoglobin S with reduced or absent hemoglobin A, depending on the type of beta-thalassemia gene.

The blood smear provides supporting clues. In sickle cell disease, the pathologist may see sickle-shaped red blood cells, target cells (red blood cells with a bullseye appearance, common in hemoglobin SC disease), and small dark spots inside red blood cells called Howell-Jolly bodies, which suggest that the spleen is no longer working normally. The complete blood count usually shows anemia (a low hemoglobin level), and the number of reticulocytes (young red blood cells) is often increased because the bone marrow is working hard to replace the cells that are breaking down.

What is sickle cell trait, and how is it different?

Sickle cell trait is not the same as sickle cell disease. A person with sickle cell trait has inherited one hemoglobin S gene and one normal hemoglobin gene. People with sickle cell trait are called carriers, and they usually have no symptoms and do not need treatment, because their red blood cells contain mostly normal hemoglobin A. On hemoglobin analysis, sickle cell trait shows more hemoglobin A than hemoglobin S, which is the opposite of the pattern seen in sickle cell anemia. Identifying sickle cell trait is still important, because two carriers can pass sickle cell disease to their children, and this information is useful for family planning. If your report shows sickle cell trait, your doctor or a genetic counselor can explain what it means for you and your family.

What happens after a diagnosis of sickle cell disease?

After sickle cell disease is diagnosed, care focuses on preventing complications, managing pain, and treating anemia. The type of sickle cell disease and the pattern of complications help guide several decisions:

Disease-modifying medicines — Hydroxyurea increases the amount of hemoglobin F, which reduces sickling and lowers the number of pain crises. Another medicine, L-glutamine, can also reduce the frequency of pain crises.
Preventing infections — Vaccinations and, in children, daily antibiotics help protect against serious infections caused by a poorly functioning spleen. Folic acid supports the production of new red blood cells.
Blood transfusions — Used to treat severe anemia and certain complications, and sometimes given regularly to lower the risk of stroke.
Potentially curative treatments — An allogeneic stem cell transplant, using blood-forming cells from a donor, can cure sickle cell disease. Newer gene therapies, which modify a person’s own blood-forming cells, have also become available for eligible patients.

Care is usually provided by a team with experience in sickle cell disease, and regular check-ups help monitor for complications and manage pain. Clinical trials of newer treatments may also be an option to discuss. Decisions about treatment are made by the care team together with the patient, based on the type of disease and the specific findings.

What is the prognosis for sickle cell disease?

Sickle cell disease is a lifelong condition, but the outlook has improved substantially with early diagnosis through newborn screening, vaccinations, hydroxyurea, and comprehensive care. Many people now live well into adulthood, although complications from blocked blood vessels and chronic anemia can still affect quality of life and life expectancy. Stem cell transplant and gene therapy offer the possibility of a cure for some people. Your outlook depends on the type of sickle cell disease, the complications you experience, and your overall care, which your health care team can explain in the context of your specific situation.

Questions to ask your doctor

What type of sickle cell disease do I have?
What did my hemoglobin analysis show, and what were the percentages of each hemoglobin?
Do I have sickle cell disease or sickle cell trait?
Was genetic testing done to confirm my exact type?
What did my blood count and blood smear show?
What complications should I watch for, and how can they be prevented?
Would hydroxyurea or another medicine be helpful for me?
Do I need vaccinations or antibiotics to prevent infections?
Am I a candidate for a stem cell transplant or gene therapy?
Should my family members be tested for sickle cell trait?
Are there clinical trials that I should consider?