Autoimmune Cytopenias

How autoimmune cytopenias happen

Normally the immune system targets germs. In autoimmune cytopenias, antibodies or immune cells attach to blood cells, which are then removed by the spleen and liver or destroyed in the bloodstream. The bone marrow often works harder to compensate, but cannot keep up. In some cases, the immune system also slows production in the marrow.

Types

Types of AIHA

• Warm AIHA: the most common; antibodies (usually IgG) act at body temperature.
• Cold agglutinin disease: antibodies (usually IgM) act in the cold, causing fingers and toes to turn blue or numb in cold weather, with anemia.

Causes

• Primary (idiopathic): no underlying cause is found, which is common in ITP in children and adults.
• Autoimmune diseases: lupus, rheumatoid arthritis and autoimmune thyroid disease.
• Blood cancers: chronic lymphocytic leukemia and lymphoma, especially in older adults.
• Infections: viral infections in children (ITP after chickenpox or other viruses), HIV, hepatitis C, H. pylori, Epstein-Barr virus and Mycoplasma (cold agglutinins).
• Immune deficiencies: common variable immunodeficiency and inherited immune dysregulation syndromes, especially in Evans syndrome.
• Medicines: certain antibiotics, quinine, heparin, some cancer immunotherapy medicines (checkpoint inhibitors) and others.
• After stem cell transplant.
• Pregnancy can trigger or worsen ITP.

Symptoms

Low platelets

• Bruising easily or without injury
• Petechiae: pinpoint red or purple spots, often on the lower legs
• Nosebleeds, bleeding gums and heavy periods
• Blood in urine or stools (rarer)

Low red cells (hemolysis)

• Fatigue, weakness and breathlessness
• Pale skin and a fast heartbeat
• Yellow skin or eyes (jaundice) and dark urine
• An enlarged spleen

Low neutrophils

• Frequent or severe bacterial infections
• Mouth ulcers and gum inflammation
• Fever, which can be the only sign of serious infection

Diagnosis

• Complete blood count with a blood film to look at cell shapes
• Reticulocyte count (young red cells), bilirubin, LDH and haptoglobin for hemolysis
• Direct antiglobulin test (DAT or Coombs test): confirms antibodies on red cells in AIHA
• Tests to exclude other causes of low counts: vitamin B12 and folate, liver function, HIV and hepatitis tests
• Tests for underlying disease: antinuclear antibodies for lupus, immunoglobulin levels, flow cytometry for lymphoma or CLL, CT scan
• Bone marrow biopsy when the cause is unclear or a marrow disorder is suspected

Treatment

Treatment depends on the type, severity and cause. Mild ITP with platelet counts above about 30,000 per microliter and no bleeding is often monitored without treatment.

• Corticosteroids such as prednisone are usually first-line for ITP and warm AIHA.
• IV immunoglobulin (IVIG) for a rapid rise in platelets, for example with bleeding or before surgery.
• Rituximab, which removes antibody-producing B cells, for relapsing or steroid-resistant disease and cold agglutinin disease.
• Thrombopoietin receptor agonists (eltrombopag, romiplostim, avatrombopag) to boost platelet production in ITP.
• Fostamatinib for chronic ITP.
• Sutimlimab, a complement inhibitor, for cold agglutinin disease.
• Immunosuppressants such as mycophenolate, azathioprine or sirolimus, often used in Evans syndrome.
• G-CSF injections to raise neutrophils when infections are severe.
• Splenectomy for selected people with chronic ITP or warm AIHA not responding to medicines.
• Transfusions in emergencies, plus folic acid supplements in hemolysis.
• Treating the cause, such as lymphoma, CLL, lupus or H. pylori.

Day-to-day precautions

• Avoid aspirin, ibuprofen and other NSAIDs when platelets are low, unless your hematologist advises otherwise.
• Avoid contact sports with very low platelets.
• In cold agglutinin disease, keep warm, especially hands and feet.
• With neutropenia, treat any fever as urgent.
• Wear medical ID if you have chronic disease or have had a splenectomy, and keep vaccinations up to date.

Outlook

ITP in children usually resolves within weeks to months. In adults it often becomes chronic but is controllable. Warm AIHA responds to steroids in most people, though relapses are common. Evans syndrome tends to be chronic and relapsing and needs long-term specialist care.

Frequently asked questions

What are autoimmune cytopenias?

They are conditions in which the immune system destroys the body's own blood cells, lowering platelet, red cell or white cell counts. The main types are immune thrombocytopenia, autoimmune hemolytic anemia and autoimmune neutropenia. Evans syndrome is when more than one type occurs.

What is Evans syndrome?

Evans syndrome is a rare autoimmune condition in which the immune system destroys both red blood cells and platelets, and sometimes white cells. It tends to be chronic, with flares and remissions. It is sometimes linked to immune deficiency or lupus and needs care from a hematologist.

Are autoimmune cytopenias serious?

They range from mild and self-limiting to life-threatening. Very low platelets can cause serious bleeding, severe hemolysis can strain the heart, and very low neutrophils raise the risk of dangerous infections. With treatment, most people are well controlled.

Can autoimmune cytopenias be cured?

Some resolve completely, especially ITP in children and cytopenias caused by a medicine or infection. Chronic forms in adults are usually controlled rather than cured, though some people achieve long remissions after rituximab or splenectomy.