What is Paediatric Evans Syndrome? 

Paediatric Evans Syndrome is a rare disorder that affects the blood and immune system of children of any age group. Clinically, a child affected with the syndrome will be fatigued, may display a yellow colouring of the skin and eyes (jaundice), a paleness to their skin or inner eyelids and gums (pallor) and bleeding from the mucosal linings of the body, like the mouth, nose and gums.¹

Specifically, to be diagnosed with paediatric Evans Syndrome, the child will be experiencing concurrent or sequential occurrences of autoimmune haemolytic anaemia and immune thrombocytopenia in the absence of an underlying aetiology. This means they have lower numbers of red blood cells or platelets than they should, without an underlying condition being the cause of this.² Treating Evans syndrome is essentially based on the treatments available for autoimmune haemolytic anaemia and immune thrombocytopenia. As the management of these two conditions is being improved, it causes the mortality rate associated with both conditions to be lower than the mortality rate of an isolated case of Evans syndrome. This suggests the need to improve the way that Evans Syndrome is being managed.³

Autoimmune haemolytic anaemia 

Autoimmune haemolytic anaemia means that a person has fewer red blood cells than they should. Essentially, the body is producing autoantibodies (antibodies against our own helpful cells) that target red blood cells and destroy them. This is a problem because it leads to anaemia. Our red blood cells have a really important job: to carry oxygen around our bodies and drop it off. When we don’t have enough red blood cells or the ones we do have are not very healthy, it means that the oxygen isn’t being transported around the body properly. The term ‘haemolytic’ means the haem (red blood cells) cells are lysed (broken). Autoimmune haemolytic anaemia can be categorised into warm, cold or mixed subtypes. This is based on the temperature at which those autoantibodies are most active. The most common subtype is warm. If you read more about autoimmune haemolytic anaemia, it is often abbreviated to AIHA in scientific literature. If there is a letter (w/c/m) in front of this, that is referring to the subtype.^4,5

Immune thrombocytopenia 

Immune thrombocytopenia means that a person has fewer platelets than they should. Platelets are small pieces of cells; they are one of the components of our blood with the specific job of helping stop bleeding by forming clots. When someone has a low platelet count, they are likely to bruise more easily, have nosebleeds, or bleed for longer than most other people if they cut themselves. This is termed thrombo (clot, from the Greek 'thrombos' – referring to platelets) – 'cyto' (cell) – 'penia' (lack of or reduced). The reason for this reduction in platelets is often due to them being destroyed or not enough being made. Scientists have worked out that this is sometimes because antibodies (part of our immune system) react with glycoproteins (sugar molecules stuck to the outside of proteins) on the surface of the platelets, meaning they don’t survive for as long as they should. Alternatively, the reduction in platelet quantity can be caused by damage to a cell type called megakaryocytes (found within the bone marrow), which become platelets as they mature. When treating people with immune thrombocytopenia, the main goals are to reduce and prevent severe episodes of bleeding and give the individual the best health-related quality of life that we can.^6,7

Available treatments 

There are a variety of treatments to be discussed in relation to Paediatric Evans Syndrome. The main ones are highlighted below. It should be noted that there are other less commonly used treatments, including mycophenolate mofetil and cyclosporine, as well as other third-line treatments such as cyclophosphamide, alemtuzumab, thrombopoietin-receptor agonists and haemopoietic stem cell transplants.¹

Corticosteroids 

Corticosteroids are a type of medicine which mimic the hormones that our bodies naturally make, and in this case, they help to make the immune system less overactive, meaning those autoantibodies are less able to attack the red blood cells. This should result in reduced depletion of red blood cells and platelets.¹ When treating Pediatric Evans Syndrome, the corticosteroid most often used is Prednisone. Corticosteroids should only be used for up to three to four weeks because of the associated side effects. Side effects include insomnia, weight gain and an increased risk of infection.³

Intravenous Immunoglobulin 

Intravenous immunoglobulin is a treatment which involves injecting the patient directly into their vein with antibodies. In Evans Syndrome, this injection of antibodies helps to increase the levels of both red blood cells and platelets. There are different types of antibodies, and for intravenous immunoglobulin treatment, it is normally IgG antibodies that are used. These IgG antibodies help to block a certain receptor on the surface of the immune cell macrophages, stopping them from being able to target and deplete red blood cells and platelets.^1,3

Rituximab 

Rituximab is a monoclonal antibody therapy, meaning it is a type of protein made by scientists in the lab. It has been engineered to target CD20, found on the surface of immune cells. This means that it also helps to calm down the overactive immune system seen in patients with Evans Syndrome. When rituximab binds to CD20, this marks those immune cells for destruction, which is good for Evans syndrome because it means the immune cell can no longer produce autoantibodies.¹

Splenectomy 

A splenectomy is when the spleen is surgically removed. The spleen is an organ in our bodies which filters blood, removing any old or damaged blood cells, and also houses our immune cells, which produce and interact with autoantibodies. So when the spleen is removed, less red blood cells and platelets will be destroyed. This helps to reduce the autoimmune haemolytic anaemia and immune thrombocytopenia; in addition, fewer autoantibodies can be produced. As you can imagine, a splenectomy is mostly only considered as a treatment option if other treatments outlined above have not been successful.³

Treatment challenges 

Data availability 

Unfortunately, there is a lack of data describing the effectiveness of Rituximab and splenectomy. This is because the syndrome is rare, and that makes it tricky for researchers to recruit enough patients for a clinical trial which is large enough to be valuable. To make it even more challenging, different patients are affected in different ways! This means that a lot of the understanding we do have about treatments for Evans syndrome comes from retrospective studies or specific case studies, which are not as useful to us on a larger scale.³

Complications of corticosteroids 

There are, unfortunately, a whole host of complications associated with corticosteroid treatment. For example, it can cause part of a bone to die due to a loss of blood supply to the area, which is known as avascular necrosis; gastrointestinal bleeding, which is the bleeding from any part of the digestive system; heart attack or heart failure; strokes and other brain-related issues due to problems with blood flow to the brain; and eye problems such as glaucoma or cataracts, which can result in vision loss.⁸

Infection 

When a child has a total splenectomy, this increases the risk of having an overwhelming infection afterwards. This is a life-threatening infection which progresses really quickly, often only taking hours to become serious. The infection can get severe, it becomes sepsis, which can lead to organ failure and even death.⁹ In addition, a splenectomy can increase the chances of hepatocellular carcinoma, a type of cancer.¹⁰

Thrombosis risk 

Thrombosis is the medical term for a blood clot; this is where platelets, red blood cells and a protein called fibrin combine to create a lump within a blood vessel. People with Evans syndrome already have an increased risk of thrombosis; with autoimmune haemolytic anaemia we already know that the red blood cells get destroyed, this leaves lots of fragments floating around in the bloodstream. These fragments are called pro-coagulants- this means they increase the thickening of the blood and the chances of a blood clot forming. Importantly, many of the treatments for Evans syndrome also increase the risk of thrombosis. Intravenous immunoglobulin increases blood thickness, slowing circulation and increasing the chances of a clot forming, as well as activating platelets, which are part of clot formation; corticosteroids increase blood pressure, which increases thrombosis risk; the spleen is supposed to filter out excess pro-coagulant particles, so after a splenectomy the risk of thrombosis is also increased.^11,12

Summary 

Pediatric Evans Syndrome is a rare and complex autoimmune disorder that remains a significant challenge in paediatric haematology. By definition, it involves the combination of autoimmune haemolytic anaemia and immune thrombocytopenia, leading to fatigue, pallor, jaundice, and an increased risk of bleeding. While treatment options such as corticosteroids, intravenous immunoglobulin, rituximab, and splenectomy are available, each carries important limitations and risks. Corticosteroids cannot be used long-term due to severe side effects, rituximab and splenectomy lack high-quality trial data, and both splenectomy and immunosuppressive therapies leave patients more vulnerable to life-threatening infections. Additionally, Evans Syndrome itself, together with its treatments, increases the risk of thrombosis, further complicating management. Because of its rarity and variability, research into Evans Syndrome is limited, resulting in uncertainty over the best treatment strategies. Continued international collaboration, patient registries, and clinical research are therefore vital to improve outcomes and quality of life for children affected by this condition.