Doctors can classify hemolytic anemia as warm or cold depending on the temperature at which the relevant antibodies are reactive. Warm subtypes are far more common, though symptoms and treatment are similar.

Hemolytic anemia is a type of blood cell disorder in which your body destroys red blood cells more quickly than it can produce new ones.

The severity and onset can vary, but common symptoms include weakness, fatigue, and enlargement of the liver and spleen.

If you’ve recently received a diagnosis of hemolytic anemia, a doctor may have classified it as “warm” or “cold.” These two types of autoimmune-related hemolytic anemia usually develop in adulthood.

Keep reading to learn the differences between the two subtypes, including their symptoms, treatment options, and overall outlook.

Hemolysis is your body’s natural process of removing old or dysfunctional red blood cells. Certain health conditions, medications, or recent infections can sometimes cause hemolysis to go into overdrive, destroying more red blood cells than it should. This can cause anemia.

Some cases of hemolytic anemia are autoimmune, meaning that they develop when your immune system mistakenly attacks healthy red blood cells. Unlike inherited hemolytic anemia, autoimmune forms typically develop in adulthood.

Doctors may classify autoimmune hemolytic anemia as either “warm” or “cold.”

Warm subtypes create autoantibodies when your body temperature is 98.6ºF (37ºC) or higher. These autoantibodies attach to red blood cells and destroy them. Warm antibody hemolytic anemia (wAIHA or WAHA) is the most common subtype, affecting an estimated 1 to 3 out of 100,000 adults in the United States.

Cold hemolytic anemia, on the other hand, destroys red blood cells at temperatures between 32ºF to 39ºF (0ºC to 4ºC). Also known as cold agglutinin disease (CAD), this type of hemolytic anemia is rarer.

Symptoms of hemolytic anemia may include:

  • weakness
  • fatigue
  • pale skin
  • shortness of breath
  • dizziness
  • heart palpitations

Overall, the symptoms of warm and cold hemolytic anemia are similar and largely the same as those of anemia more generally.

There are a few exceptions. For example, hemolysis triggered by cold temperatures may cause cold fingers and toes, which may turn red, purple, or brown depending on your natural skin tone. CAD can also cause cold sweats.

WAHA is more likely than cold types to cause the skin and white of your eyes to turn yellow (jaundice) and your urine to turn dark.

To diagnose anemia, a doctor will perform a complete blood count (CBC). They’ll usually combine this with a peripheral blood smear which allows them to examine the appearance of red blood cells under a microscope.

Additional tests to indicate hemolysis include LDH, bilirubin, and haptoglobin tests. Doctors will likely order a direct antiglobulin test (aka DAT or Coombs test) to determine if hemolysis is due to an immune process.

Distinguishing between warm and cold hemolytic anemia is complicated, and requires the identification of specific immunoglobulins through a DAT.

Given the autoimmune nature of warm and cold hemolytic anemia, both subtypes require treatment to stop the immune system from creating antibodies that destroy red blood cells. Treatments are similar across both subtypes.

Most people respond to first-line treatments for hemolytic anemia, such as medications like prednisone, a steroid.

However, in more severe cases that don’t respond to steroids, a doctor might recommend second-line treatments, including:

  • monoclonal antibodies, such as rituximab (Rituxan)
  • immunosuppressive medications, such as azathioprine or cyclosporine
  • surgery to remove the spleen (splenectomy)

Other treatment measures may include:

Given the autoimmune nature of both warm and cold hemolytic anemia, it’s important for a doctor to diagnose these conditions accurately and for you to follow their recommended treatment plan.

Both warm and cold hemolytic anemia are treatable. When left untreated, these conditions may be fatal. According to a 2023 review, about 3% to 20% of people with WAHA die within 4 years, though a link to hemolysis is not always clear.

Unlike other types of hemolytic anemia, autoimmune forms also have higher rates of relapse.

Both warm and cold hemolytic anemia may increase your risk of developing blood clots.

What is the difference between a warm antibody and a cold antibody?

Warm antibodies react best at temperatures close to body temperature (98.6ºF or 37ºC). Cold antibodies react best at temperatures below body temperature. In the case of cold autoimmune hemolytic anemia, the antibodies tend to react around 32ºF to 39ºF (0ºC to 4ºC).

Which is more serious — warm or cold hemolytic anemia?

Both warm and cold hemolytic anemia are serious conditions that may be fatal if left untreated. However, warm hemolytic anemia is more serious because the disease activates at regular body temperatures.

Which is more common — warm or cold hemolytic anemia?

Warm hemolytic anemia is more common than cold subtypes. While WAHA affects up to 3 in every 100,000 adults, CAD affects 0.48 to 1.9 per every million people per year, depending on climate.

Both warm and cold hemolytic anemias are autoimmune and develop when your immune system attacks your red blood cells.

While the overall symptoms and treatment measures are largely the same with both types of hemolytic anemias, the onset varies. Warm subtypes occur at body temperature, while cold hemolytic anemia occurs when exposed to cold temperatures.

Given the similarities between the two conditions, only a doctor can run the appropriate tests to give a definitive diagnosis. If you’re experiencing symptoms of anemia or are concerned about a prior diagnosis, consider talking with them about a diagnosis, treatment, or management plan.