Treatment of Cold Agglutinin Disease

Cold agglutinin disease (CAD) is a rare kind of anemia, a condition that happens when your body doesn’t have enough red blood cells. With CAD, when your body temperature drops below your normal body temperature, your immune system attacks and destroys healthy red blood cells.

Doctors treat CAD in several ways, depending on how severe it is and what’s causing it. With a mild case, you may not need treatment.

Stay Warm

Because CAD is triggered by cold temperatures, you need to keep your body warm. When the weather’s chilly:

  • Bundle up well when you go outdoors.
  • Give your head, hands, and feet extra protection.
  • Wear a scarf, hat, earmuffs, and gloves, and choose socks and shoes that keep your feet toasty.
  • Use space heaters.
  • If you live in a cold climate, go somewhere warmer in the winter if you can.
  • Stay away from cold foods and drinks.

In some cases, these steps may be all you need to keep CAD under control.


If keeping yourself warm doesn’t work well enough, your doctor can choose from several drugs:

  • Rituximab: One of the most common treatments for CAD, this can stop your immune system from attacking your red blood cells. Your medical team gives it to you directly into a vein through an IV that slowly drips it into your bloodstream. That could take 2 to 4 hours, and you might need one dose a week for several weeks.
  • Bendamustine. Your doctor might recommend this along with rituximab. It can prevent harmful cells from growing. You also get it through an IV that drips it into your vein. That usually takes 30 minutes to an hour. Your medical team might give it to you 2 days a month for 4 months.
  • Fludarabine. This is another drug that can work alongside rituximab. It attacks harmful cells so they can’t multiply. You get it either through an IV or in pills. Either way, you might get it 5 days in a row, then do the same thing a month later, and so on every month for as long as your doctor says.
  • Corticosteroids. In the past, doctors sometimes treated the condition with these, but studies show they don’t help much. And they involve such a big dose that they’re not necessarily safe.
  • Bortezomib. If nothing else works, your doctor might suggest this drug that’s used to treat a kind of cancer called multiple myeloma.

Blood Transfusion

Your medical team may have to give you blood now and then to shore up your supply. When your body can’t make enough healthy blood on its own, a transfusion makes sure you have what you need. This can be especially helpful during the winter. You’ll get the blood through an IV in your arm.

Filter Your Blood

If you have a dangerous flare-up, your medical team can use a machine to filter your blood and take out a certain kind of protein (called antibodies) that is causing the illness. Your doctor may call this plasmapheresis. It’s only a short-term fix in an emergency, though. It isn’t a cure.


Doctors used to think taking out your spleen helped fight cold agglutinin disease. But they don’t recommend it anymore. It rarely does any good because your spleen isn’t where the disease attacks your blood.

Clinical Trials

Researchers are working to find better ways to fight the disease. When they think a new treatment for an illness might help, they look for volunteers to try it in what’s called a clinical trial.

If you have cold agglutinin disease, you may be able to take part in one. Talk with your doctor to see if any are going on in your area and if one might be a good match for you.


  2. Genetic and Rare Diseases Information Center: “Cold agglutinin disease.”
  3. UpToDate: “Cold agglutinin disease.”
  4. British Journal of Haematology: “How I manage cold agglutinin disease.”
  5. American College of Rheumatology: “Rituximab (Rituxan and MabThera).”
  6. American Society of Hematology: “Cold agglutinin disease,” “Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial,” “Ask the Hematologist: Management Approach to Primary Cold Agglutinin Disease.”
  7. National Organization for Rare Diseases: “Anemia, Hemolytic, Cold Antibody.”
  8. Mayo Clinic: “Blood transfusion.”
  9. National Kidney Foundation: “Plasmapheresis and Blood-type Incompatible Kidney Transplant.”

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