Hemolytic anemia

Causes and who gets it

In inherited causes, the problem is usually in the red blood cell itself:

• Cell membrane disorders: In hereditary spherocytosis, red blood cells lose their flexibility, become ball-shaped and are destroyed in the spleen.
• Enzyme deficiencies: In G6PD deficiency, fava beans, some medicines or infections can trigger sudden breakdown. Pyruvate kinase deficiency leads to ongoing breakdown.
• Hemoglobin disorders: Sickle cell disease and thalassemia.

Acquired causes are:

• Autoimmune hemolytic anemia: The immune system makes antibodies against its own red blood cells. It affects about 1 in 100,000 people each year. In half of cases it occurs alongside another disease such as lymphoma, an infection or lupus.
• Warm type: The antibody acts at body temperature; about two thirds of cases are this type.
• Cold type: The antibody attaches to red blood cells at low temperatures. Cold agglutinin disease mostly occurs in middle-aged and older people; it can also develop after mycoplasma pneumonia.
• Medicines: Some antibiotics (especially cephalosporins) and anti-inflammatory painkillers rarely cause breakdown.
• Infections such as malaria, an artificial heart valve, a mismatched blood transfusion
• Clots in small blood vessels: TTP (thrombotic thrombocytopenic purpura) and HUS (hemolytic uremic syndrome)
• PNH (paroxysmal nocturnal hemoglobinuria): A rare disease caused by a gene change that develops later in life in the bone marrow

Symptoms

Mild hemolytic anemia may cause no symptoms. Symptoms are due to the anemia and to the breakdown itself:

• Tiredness, weakness, dizziness
• Pale skin
• A pounding heartbeat and shortness of breath with activity
• Jaundice: yellowing of the skin and the whites of the eyes
• Dark urine, the color of tea or cola
• Pain in the upper left abdomen, or feeling full quickly, due to an enlarged spleen

In long-lasting (chronic) hemolysis, gallstones can form; they develop in about half of people with hereditary spherocytosis. In the cold type, the fingers and toes, the tip of the nose or the ears can turn purplish-blue in the cold. Severe, untreated hemolysis can lead to heart rhythm problems and heart failure.

Diagnosis and tests

Your doctor will ask about your medicines, any blood transfusions in recent months, and whether anyone in your family has anemia, jaundice, gallstones or an enlarged spleen. The following tests are ordered:

• Complete blood count and reticulocyte count: A reticulocyte is a young red blood cell that has just left the bone marrow; the count usually rises in hemolysis.
• Peripheral blood smear: Blood is examined under a microscope. The shape of the red blood cells gives clues to the cause; fragmented red blood cells suggest clots in small blood vessels.
• Bilirubin (especially indirect), LDH and haptoglobin: In hemolysis, bilirubin and LDH rise and haptoglobin falls. In mild breakdown they can be normal.
• Direct antiglobulin (Coombs) test: Looks for antibodies or complement (part of the immune system) stuck to the surface of red blood cells. A positive result suggests breakdown caused by the immune system.
• If needed: G6PD and pyruvate kinase enzyme tests, hemoglobin electrophoresis or HPLC, flow cytometry for PNH (a test that measures proteins on the cell surface), urine tests, and sometimes a bone marrow examination.

Treatment approach

Treatment is chosen according to the cause and severity. In some patients whose condition is mild and stable, monitoring is enough.

• Removing the trigger: If a medicine is causing the breakdown, your doctor will stop or change it; improvement often begins within 1–2 weeks. Do not stop your medicines on your own.
• Warm autoimmune hemolytic anemia: The first option is corticosteroids, which suppress the immune system; about 8 in 10 patients respond. If the response is not enough or the disease comes back, biologic medicines that target B cells, other immunosuppressants or removal of the spleen are considered.
• Cold type: The main measure is protecting yourself from the cold. If symptoms are severe, biologic medicines may be used; removing the spleen usually does not help.
• Blood transfusion: May be needed for severe anemia. In the autoimmune type, finding suitable blood can take time; in a life-threatening situation the transfusion is not delayed.
• Folic acid: In chronic hemolysis, your doctor may recommend a supplement.
• Removal of the spleen (splenectomy): Because the spleen destroys abnormal red blood cells, it is considered in selected patients.

Emergencies such as TTP are treated in hospital with plasma exchange.

Everyday life and follow-up

• Gallstones: Pain under the right ribs or in the middle of the abdomen that lasts more than 30 minutes may be due to gallstones; see a doctor. For sudden severe pain, a high fever or yellowing, go to the emergency department.
• If your spleen has been removed: The risk of a serious infection is small but lifelong. Ask your doctor about pneumococcal, flu and meningitis vaccines; preventive antibiotics may be recommended. Carry a card that shows your condition.
• Cold type: Keep your head, hands and feet warm in the cold. Before surgery, tell the team about your condition.
• Clots: Hemolysis increases the risk of a clot in a vein, especially during flare-ups. If you have pain and swelling in one leg, see a doctor the same day.
• Check-ups: Do not miss your blood counts. If you take corticosteroids for a long time, talk to your doctor about protecting your bones and stomach.

Pregnancy, children and special situations

Pregnancy: Autoimmune hemolytic anemia is rare in pregnancy; it occurs in about 1 in 140,000 pregnancies. In the mother, the condition often improves after birth. Warm-type antibodies can pass to the baby and cause anemia and jaundice in the days or weeks after birth. Care is provided jointly by hematology and obstetrics specialists. If a low platelet count occurs together with hemolysis, serious pregnancy-specific conditions are also looked for.

Blood group incompatibility between mother and baby: If the mother’s blood group is different from the baby’s, the mother can develop antibodies that destroy the baby’s red blood cells. The most severe form is Rh (D) incompatibility; it can often be prevented with blood tests during pregnancy and an anti-D injection that prevents antibodies from forming.

Children: Autoimmune hemolytic anemia in children is most common under age 5 and is usually short-lived. Anemia and jaundice in a newborn can be linked to blood group incompatibility or to inherited hemolytic anemias.

In Türkiye

For adults, the assessment can start with a family doctor (aile hekimi) or an internal medicine specialist, and for children with a pediatrician; if needed, you will be referred to hematology or pediatric hematology. The Türk Hematoloji Derneği (Turkish Society of Hematology) notes that, in a child with anemia, a family history of anemia, gallstones, an enlarged spleen and marriage between relatives is important for the diagnosis.

Law No. 3960 of 1993 on Combating Hereditary Blood Diseases covers inherited blood diseases such as thalassemia, sickle cell anemia and red blood cell enzyme diseases. Premarital hemoglobinopathy screening has been carried out in all 81 provinces since 2018.

Related pages