Introduction: Who Should Be Tested and When

If you or someone you know has sickle cell disease, regular diagnostic testing is an important part of staying healthy. In the United States, all newborn babies are screened for sickle cell disease as part of routine newborn screening programs. This early detection means that most people with the condition are diagnosed shortly after birth, often before symptoms appear. This gives doctors the chance to start preventive care early, which can reduce the risk of serious infections and other problems down the line.^[2]

However, diagnosis doesn’t stop after the initial newborn screening. For people already diagnosed with sickle cell disease, seeking medical evaluation becomes necessary whenever new or worsening symptoms appear. The most common reason people with this condition visit emergency departments is a painful episode known as a sickle cell crisis. This happens when crescent-shaped red blood cells clump together and block blood vessels, cutting off oxygen to tissues and organs.^[1]

If you have sickle cell disease, you should seek immediate medical attention when you experience sudden, severe pain that doesn’t respond to home treatment. Other warning signs include a high temperature above 38°C, severe vomiting or diarrhea, sudden breathing difficulties, a severe headache or dizziness, sudden confusion or drowsiness, weakness on one or both sides of the body, or sudden changes in vision. Any of these symptoms could signal a serious complication that requires urgent evaluation.^[7]

People without a known diagnosis should consider testing if they have a family history of sickle cell disease or if they belong to ethnic groups where the condition is more common, such as people with African or Caribbean family backgrounds. Blood tests can be carried out at any age to check for sickle cell disease or to find out if you’re a carrier of the gene that causes it.^[7]

Classic Diagnostic Methods for Sickle Cell Disease

Blood Tests to Identify Abnormal Hemoglobin

The main way doctors diagnose sickle cell disease is through a blood test that looks for abnormal hemoglobin—the protein inside red blood cells that carries oxygen. In people with sickle cell disease, this protein has an unusual form called hemoglobin S (HbS). When laboratory staff examine a blood sample, they can identify the presence of this abnormal hemoglobin and confirm the diagnosis.^[3]

In adults, blood samples are typically taken from a vein in the arm. For young children and babies, the blood sample is usually collected from a finger prick or heel stick. The sample then goes to a laboratory where it’s screened for the sickle cell form of hemoglobin. This same type of test can also tell whether someone is a carrier of the sickle cell gene, known as having sickle cell trait, which means they don’t have the disease themselves but could pass the gene to their children.^[11]

Genetic testing can also be used to confirm the diagnosis and determine the exact type of sickle cell disease a person has. There are several different types, including HbSS (the most common and usually most severe form), HbSC, and HbS beta thalassemia. Knowing which type you have helps doctors predict how severe your symptoms might be and plan the best treatment approach.^[5]

Evaluating a Sickle Cell Crisis

When someone with sickle cell disease comes to the hospital experiencing a crisis, doctors need to perform a thorough evaluation to determine how severe the episode is and whether there are any complications. This evaluation typically begins with a complete physical examination, during which the doctor will check for signs of pain, swelling, breathing difficulties, and other symptoms.^[1]

A full laboratory workup is usually necessary during a crisis. This includes several blood tests that help doctors understand what’s happening in your body. A complete blood count (CBC) measures the number and types of cells in your blood, which can show whether your red blood cell levels have dropped dangerously low. A comprehensive metabolic panel (CMP) checks how well your organs, especially your kidneys and liver, are functioning. Liver function tests provide additional details about whether the crisis is affecting your liver. A reticulocyte count measures how many young red blood cells your bone marrow is producing, which helps doctors understand whether your body is trying to replace damaged cells.^[1]

In some cases, doctors may also need to determine your blood type. This is particularly important if you might need a blood transfusion to help manage the crisis. Blood transfusions can increase the number of healthy red blood cells in your body, reducing symptoms and preventing complications.^[1]

Imaging Tests

Imaging tests help doctors see what’s happening inside your body during a sickle cell crisis. Different types of imaging can reveal whether sickled cells have caused damage to your bones, organs, or blood vessels. Common imaging tests include ultrasound, which uses sound waves to create pictures of your organs and blood vessels. Doctors might use a special type called Doppler ultrasound to check blood flow through your vessels.^[1]

Magnetic resonance imaging (MRI) creates detailed pictures using magnets and radio waves. This test is particularly useful for looking at soft tissues, organs, and blood vessels. It can help identify areas where blood flow has been blocked or where tissue damage has occurred. MRI scans don’t use radiation, making them safer for repeated use, especially in children who may need many scans over their lifetime.^[1]

Regular ultrasound exams are also used outside of crisis situations. For example, doctors may use a special ultrasound technique called transcranial Doppler ultrasonography to measure blood flow to the brain in children. This painless test can be performed in children as young as two years old and helps identify those at higher risk of stroke. If the test shows reduced blood flow, regular blood transfusions may be recommended to lower that risk.^[11]

Additional Diagnostic Evaluations

Beyond the basic tests done during a crisis, people with sickle cell disease need regular screening for various complications that can develop over time. For instance, yearly eye examinations starting at age ten are important to check for damage to the retina—the light-sensitive tissue at the back of the eye. Sickle cells can block tiny blood vessels in the eye, leading to vision problems if not detected and treated early. Ideally, these examinations should be done by an eye doctor who specializes in diseases of the retina.^[16]

Your healthcare provider may also recommend testing to assess how well your organs are working. This might include checking your kidney function, lung capacity, and heart health. Because sickle cells can damage these organs over time, regular monitoring helps catch problems before they become severe. These evaluations become part of your routine care, typically performed during your regular checkups every six to twelve months.^[1]

Diagnostics for Clinical Trial Qualification

If you’re considering joining a clinical trial to test new treatments for sickle cell disease, you’ll likely need to undergo additional diagnostic testing. Clinical trials have specific requirements about who can participate, and these requirements help researchers ensure that the treatment being studied is safe and that the results will be meaningful. The exact tests required depend on the specific trial, but there are some common evaluations that most studies need.^[14]

At a minimum, clinical trials for sickle cell disease usually require confirmation of your diagnosis through blood testing that identifies the presence of hemoglobin S. Researchers need to know exactly which type of sickle cell disease you have, because different types can respond differently to treatment. Genetic testing may be part of this confirmation process to determine whether you have HbSS, HbSC, or another form of the disease.^[3]

Most clinical trials also require baseline blood studies before you can enroll. These establish your starting point so researchers can track how the experimental treatment affects your condition over time. Baseline tests typically include a complete blood count to measure your hemoglobin levels and count different types of blood cells, liver function tests to check how well your liver is working, kidney function tests to assess your kidneys, and a reticulocyte count to see how actively your bone marrow is producing new red blood cells. These baseline values help researchers understand whether you’re a good candidate for the study and give them comparison points for measuring the treatment’s effects.^[12]

Some trials may require imaging studies as part of the screening process. For example, if the trial is testing a treatment aimed at preventing stroke, you might need an MRI or transcranial Doppler ultrasound to evaluate your current stroke risk. If the study focuses on preventing lung complications, you might need chest X-rays or lung function tests. These specialized tests help match patients to trials where they’re most likely to benefit from the experimental treatment.^[14]

Clinical trials may also track how often you experience painful crises. To do this, researchers might ask you to keep a diary of your pain episodes, including when they start, how long they last, where the pain is located, and what treatments you use. This information helps researchers understand whether the experimental treatment is reducing the frequency or severity of crises. Some studies provide participants with tools to record this information, such as smartphone apps or paper logs.^[17]

Throughout your participation in a clinical trial, you’ll undergo regular monitoring with many of the same tests used in routine care, but usually more frequently. The study team will carefully track any changes in your condition and watch for both positive effects of the treatment and any unwanted side effects. This close monitoring is one of the benefits of participating in research—you receive very careful medical attention throughout the study period.^[12]