Hemolytic Anemia: When Red Blood Cells Are Destroyed Too Quickly

How hemolysis causes anemia

The bone marrow can increase red cell production up to about 6 to 8 times normal. Anemia develops when destruction exceeds this capacity. Destruction can happen:

• inside blood vessels (intravascular), releasing hemoglobin into the blood and urine, which turns urine dark
• in the spleen and liver (extravascular), where damaged or antibody-coated cells are removed; this is more common and often causes an enlarged spleen

Breakdown of hemoglobin produces bilirubin, which causes jaundice and can form gallstones.

Causes

Inherited

Acquired

• Autoimmune hemolytic anemia: antibodies attack red cells. Warm type is linked to lupus, lymphoma, chronic lymphocytic leukemia or medicines; cold agglutinin type to infections such as mycoplasma and to lymphoproliferative disorders.
• Drug-induced: penicillins, cephalosporins, quinine, dapsone, rasburicase and others.
• Infections: malaria, babesiosis, clostridium, severe sepsis.
• Microangiopathic hemolytic anemia: red cells shredded in small vessels, as in TTP, HUS, DIC, HELLP syndrome and malignant hypertension.
• Mechanical: artificial heart valves, long-distance running ("march hemoglobinuria").
• Transfusion reactions and Rh or ABO incompatibility in newborns.
• Paroxysmal nocturnal hemoglobinuria: a rare acquired stem cell disorder.
• Toxins: snake venom, lead, copper (Wilson disease).

Symptoms

• tiredness, weakness and shortness of breath on exertion
• pale skin
• jaundice: yellow skin or whites of the eyes
• dark urine, tea- or cola-colored
• fast heartbeat
• enlarged spleen causing left upper belly fullness
• gallstones
• leg ulcers in some inherited types

Symptoms may come on gradually or suddenly, as in a hemolytic crisis.

Diagnosis

Blood tests confirm hemolysis and help find the cause:

Further tests include hemoglobin electrophoresis, G6PD and other enzyme assays, flow cytometry for PNH and membrane studies.

Treatment

Treatment depends on the cause:

• Autoimmune (warm): steroids first, then rituximab or other immunosuppressants; splenectomy in some cases.
• Cold agglutinin disease: keeping warm, rituximab-based treatment, and sutimlimab, a complement inhibitor.
• Drug-induced: stopping the drug.
• G6PD deficiency: avoiding triggers such as fava beans and certain medicines.
• Hereditary spherocytosis: folic acid; splenectomy for moderate to severe disease.
• Sickle cell disease and thalassemia: specialist care including hydroxyurea, transfusions, iron chelation and newer therapies, and in some cases gene therapy or stem cell transplant.
• TTP: emergency plasma exchange and other therapies.
• Supportive care: blood transfusion for severe anemia, folic acid supplements, treatment of gallstones.

Outlook

The outlook varies widely with the cause. Many people with mild inherited forms live normal lives. Acquired forms often resolve once the trigger is removed or the immune process is controlled. Some, such as TTP, are life-threatening without urgent treatment.

Frequently asked questions

What causes hemolytic anemia?

It can be inherited, as in sickle cell disease, thalassemia, hereditary spherocytosis and G6PD deficiency, or acquired from autoimmune conditions, certain medicines, infections, transfusion reactions, mechanical heart valves or conditions such as TTP and HUS.

What are the signs of hemolytic anemia?

Signs include tiredness, shortness of breath, pale skin, yellowing of the skin and eyes, dark urine, a fast heartbeat and an enlarged spleen. Blood tests typically show low hemoglobin, high reticulocytes, high bilirubin and LDH, and low haptoglobin.

Is hemolytic anemia serious?

It can range from mild to life-threatening. Mild forms may need no treatment, while sudden severe hemolysis, TTP or HUS are emergencies. The seriousness depends on the cause and how quickly red cells are destroyed.

Can hemolytic anemia be cured?

Acquired forms can often be cured by removing the trigger, treating an infection or controlling the immune response. Inherited forms are usually lifelong but manageable, and some, such as sickle cell disease, can now be cured with stem cell transplant or gene therapy in selected people.