Treatment options

discuss all pros and cons with your medical professionals.

SPECIAL NOTE: Please be aware that all treatments, including blood transfusions, can have side effects, some known and others yet to be discovered.

Treatments designed to lower the immune system in CAD patients can activate dormant viruses such as Cytomegalovirus, CMV, a type of herpes, or PML, Progressive Multifocal Leukoencephalopathy, or others. Also, some treatments can create an environment for new infections or viruses to arise. Before embarking on any treatment, we urge you to do as much research as you can on the web or library and to discuss all pros and cons with your medical professionals.

With CAD, no treatment is usually necessary when the patient’s degree of anemia is mild. Blood checks are essential as well as a daily dosage of folic acid and avoidance of exposure to cold.

Black Box Warning for Procrit, Epogen, and Aranesp

These erythropoietins are sometimes successful in raising hemoglobin levels in some with CAD but aggressive use of erthropoeisis-stimulating agents to raise hemoglobin to a target of 11g/dL or greater increases the risk of death, serious cardiovascular and thromboembolic reactions. If prescribed by your medical professional, remind him/her of the above warning and ask to use the smallest possible dose necessary to prevent the need for red blood cell tranfusions.

Splenectomy is usually effective in helping warm agglutinins but is an ineffective therapy for CAD.

Prior to the use of rituximab (see below), corticosteroids and immunosuppressive treatments, alkylating agents, and interferon had been used, with short-lived results and undesirable side effects.

Blood transfusions of washed red cells are sometimes necessary as a temporary measure when the hemoglobin gets very low – 7 or lower and the antibody titer is high. 

The blood should be warmed to prevent new red cells from being coated with antibodies.

Plasma exchange (also known as plasmapheresis or PP), which involves filtering blood to remove antibodies, is sometimes helpful when other treatments fail. This too is a short-lived measure.

Rituximab (Rituxan® or Mabthera®) is currently the treatment of choice. A round of treatment is normally four infusions that are given one per week for 4 weeks. Sometimes a second round of four infusions is prescribed. 

There is a risk with the initial dose due to the possibility of a serious allergic reaction. Medical facilities are well aware of this and take special precautions prior to the infusion.

Rituximab is a single agent monoclonal antibody designed to kill off the B-cells which make the antibodies that destroy the red cells. With the destruction of B-cells, the hemoglobin rises. In time, in most cases, the number of B-cells will again increase and it may become necessary to retreat with rituximab or another single agent monoclonal antibody.

One can have side-effects including fatigue following Rituxan. Please read the Stories Pages.

For those of you concerned about Rituxan (rituximab) reactions, there’s a test called HAMA (human anti-mouse antibodies) which can determine if patients have pre-existing human anti-mouse antibodies or developed them due to recent treatments with mAb (monoclonal antibodies) drugs such as Rituxan. 

Discuss with your medical professional.

Rituximab plus oral Cytoxan/Sendoxan (cyclophosphamide) and other immunosuppressive drugs are used in combination for some stubborn cases.

Rituximab plus oral fludarabine.

Rituximab plus oral Fludarabine is another treatment that has yielded promising results in a recently (2010) completed study by Sigborn Berentsen, M.D., PhD. and et al in Norway.

See our Links Page “High Response Rate and Durable Remissions Following Fludarabine and Rituximab Combination Therapy for Chronic Cold agglutinin Disease” where you can download this report.

There are potential side effects which need to be taken into account by your medical practitioner. Dr. Berentsen has said “As you will read, it is a considerably more aggressive therapy than Rituximab single agent and, therefore, potentially more toxic; and we will be cautious in using it in very old and frail patients (e.g., people over 80-85 suffering from other diseases at the same time).”

In the U.S., the research is being done through the NIH.

Rituxan Retreatment

Drs. Berentsen, Ulvestad, and Tjonnfjord write that in their experience with CAD patients, even repeated treatment with rituximab has been well tolerated. (see our Links page “B-Lymphocytes as targets for Therapy…” 2007).

According to recent published reports, there are several new single agent drugs like Rituxan which are either in clinical trials or have been approved for use in Non-Hodgkins Lymphoma, Multiple Myeloma, Chronic Lymphocytic Leukemia, Rheumatoid Arthritis, Lupus and other autoimmune diseases and may have application for CAD.


For those with CAD requiring heart surgery or any type of invasive surgery, you need to be certain to be kept warm and any fluids infused or any necessary procedures must be performed under warm temperature conditions. See the links page for a description of a heart bypass on a CADdy.


You need to be aware of the insidiousness of CMV (cytomegalovirus). It is a dormant virus that can affect those with a weakened immune system.

New Drugs for B-Cell Diseases


The current trend is away from chemotherapy and towards using monoclonal antibodies to treat Blood Cancers and Autoimmune Diseases. There are several new drugs in the pipelines, some approved already for blood cancers–B-Cell chronic lymphocytic leukmias, lymphomas, myelomas and some are showing promise in clinical trials.

These drugs may have potential application for refractory (relapsed) CAD and other autoimmune diseases such as rheumatoid arthritis and multiple sclerosis.

One is oral Imbruvica (ibrutinib) a BTK inhibitor, another is Zydelig (Idelalisib) tablets. Gazyva (obinutuzumab) (GA 101) and Arzerra (ofatumumab) (Hu-Max CD-20) a humanized monoclonal antibody most similar to Rituxan. As with many drugs, these have risks of severe toxicities and are not to be used except in stubborn or more severe cases and as determined by your medical professionals. Some have been tested to be used in combination with chemos and/or Rituxan. Rituxan is still the treatment of choice for CAD in addtion to folic acid and keeping warm.

There’s much information for you to learn about the above drugs on the internet.