Introduction 

Evans syndrome (ES) is an autoimmune condition that is very difficult to diagnose. In this condition, the immune system attacks the body’s own cells. The patient’s red blood cells (RBC), platelets, and sometimes white blood cells are attacked. These cells play a crucial role in carrying oxygen, preventing bleeding and fighting infection.¹ 

There is no single test that confirms the diagnosis. Instead, doctors have to rely on a combination of symptoms, diagnostic tests, as well as the exclusion of other similar conditions. The early detection and diagnosis of ES are extremely important, so treatment can be started as soon as possible and the effects of the condition can be stopped. 

What is evans syndrome?

To make sense of how Evans Syndrome is diagnosed, it helps to understand what the condition actually is. Rather than being a single disease, Evans Syndrome is essentially a blend of two autoimmune blood disorders: autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP).²

Autoimmune haemolytic anaemia

Red blood cells help carry oxygen around the body. In AIHA, the body mistakenly thinks that the red blood cells are foreign cells, and your immune system starts attacking them. Eventually, too many red blood cells will be destroyed, and the body will no longer be able to carry enough oxygen around the body. This can lead to symptoms such as tiredness, shortness of breath and jaundice.³

Immune thrombocytopenia

Platelets are essential to stop bleeding when you get a cut or bruise; they help the blood clot. However, in ITP, the immune system attacks and destroys platelets, similarly to AIHA. With fewer platelets, your blood cannot clot as well as it should, meaning that even small cuts or bumps will cause excessive bleeding or bruising. It is very common for you to experience more nosebleeds and bleeding gums than usual.⁴ 

The fact that both of these conditions need to overlap in order for you to be diagnosed with ES means that it is very rare. It can affect both children and adults, but it is more frequently observed in patients with primary immune deficiencies.⁵ 

Most individuals who are diagnosed with this condition have it for the rest of their lives (chronic) with periods of exacerbation and remission.⁶

Diagnostic criteria

Clinical signs and symptoms⁷

Signs of low platelets

• Unusual bruising 
• Tiny red or purple spots on the skin called petechiae
• Bleeding from the gums, nose or other mucous membranes 
• Heavy periods in women 

Signs of anaemia 

• Pale skin 
• Tiredness and weakness 
• Feeling lightheaded or dizzy 
• Shortness of breath 

Signs of red blood cell breakdown

• Yellowing of the skin and eyes, called jaundice 
• Dark yellow urine 

Laboratory tests

As mentioned above, the diagnosis of ES heavily relies on findings from numerous laboratory tests. This is because the signs and symptoms patients present with are very non-specific and can occur in countless other conditions. The tests will provide the team of specialists with a snapshot of what is going on inside the body and whether the results align with the diagnosis. 

It is vital to remember that there is not one specific test that will confirm a diagnosis. There has to be a pattern of results that will point towards ES whilst ruling out other conditions. 

Full blood count

This test measures the levels of many different components of blood, but the key ones to focus on, in this context, are the levels of red blood cells, platelets and white blood cells. The key findings will be the low levels of red blood cells and platelets. There may or may not be low levels of white blood cells alongside this.⁸

Reticulocyte count 

Reticulocytes can be described as ‘baby red blood cells’ that will develop into RBCs. In ES, patients will have a raised reticulocyte count as the body is constantly trying to replace the cells that are being attacked and destroyed.⁹ 

Lactate dehydrogenase

Lactate Dehydrogenase (LDH) is an enzyme that is produced when red blood cells break down. Doctors are looking for an increase in the LDH levels, which will signal to them that there is damage being done to RBCs.⁵

Bilirubin

This is another component that is released into the blood when RBCs break down. It is a yellow pigment, which can also present as jaundice on the patient's skin and eyes. A high level of bilirubin in the blood indicates that red blood cells are being broken down.¹⁰

Haptoglobin

When red blood cells are broken down, they release haemoglobin into the blood. This haemoglobin binds to haptoglobin. The compound is cleared by the liver, and as a result, the levels of haptoglobin will be low in patients with ES.¹⁰

Direct Antiglobulin Test (DAT)

This test is often called the Coombs test, and it is one of the most important tests when diagnosing ES. This test checks whether there are antibodies attached to the red blood cells. The test looks for antibodies made by the immune system that attach to red blood cells and mark them for destruction. A positive DAT suggests that the patient's immune system is attacking itself.²

Bone marrow examination 

The bone marrow is a soft and spongy tissue which is found in the bone, and this is where all of the blood cells are made. The examination will require doctors to take out a small sample of bone marrow, usually from the hip, and this is examined under a microscope. In a patient with ES, the sample will show that the bone marrow is active and still producing cells. Although this may indicate that there are no problems, if all the other results are positive, it shows the body is trying to quickly replace the other cells that are being destroyed.¹

Excluding other causes 

Many other conditions can mimic similar laboratory results to those seen in ES. Some of the main conditions that doctors check for are:¹⁰ 

• Infections such as HIV or Hepatitis 
• Other autoimmune diseases, such as systemic lupus erythematosus (SLE) 
• Blood cancers such as leukaemia or lymphoma 
• Chemotherapy 

What else could it be?

Sometimes the diagnostic process will suggest that there is no evidence of ES. However, if a patient is showing similar symptoms and has skewed blood results, there are a few possibilities of what the patient couldhave:¹⁰

Thrombotic microangiopathy

Tiny blood clots form in the blood vessels, using up platelets in the process. As red blood cells try to get past these clots, they will become damaged. The low platelet and RBC count mimics ES; however, the DAT will be negative as the RBCs are mechanically being broken down, unlike in ES, where they are destroyed by the immune system. 

Vitamin B12 deficiency

A lack of vitamin B12 can cause anaemia and sometimes low platelets. On blood tests, this can look confusing because the results sometimes suggest RBCs are breaking down, like in ES. However, the RBCs in vitamin B12 deficiency are much larger than normal. 

Myelodysplastic syndrome 

These are disorders where the bone marrow stops working properly. People with MDS may develop anaemia and low platelets, which can look a lot like ES. The difference is that in MDS, the body is not producing enough new red blood cells, and a bone marrow test can prove this. 

Summary

This condition is a rare and complex autoimmune condition. Doctors have to mainly rely on a combination of clinical signs and laboratory results. Low red blood cells and platelets, as well as high bilirubin and LDH, are indicative of a diagnosis. A bone marrow examination also usually reveals that blood cells are still being produced, which suggests the problem is that the cells are being destroyed, not a failure in production. Many other conditions can mimic these results, including infections, vitamin deficiencies and bone marrow disorders. This means that recognising these patterns early is vital so that treatment can begin as soon as possible.