Experts Share Guidelines for Diagnosis, Treatment of CAD, Other Autoimmune Hemolytic Anemias

Autoimmune hemolytic anemia (AIHA) experts gathered in Vienna, Austria, in November 2017 for the First International Consensus Meeting with the goal of summarizing current research into diagnosis and treatment of the rare genetic disorders.

Now, after three subsequent meetings at medical conferences, the researchers and physicians have published their conclusions and offered a unified approach to understanding AIHAs.

The goal for the consensus meeting was not to create a strict guideline for diagnosis and treatment, but to organize the various outlets of research into AIHAs (scientific studies, clinical trials, and more) with the hope of offering recommendations and providing a launching point for future avenues of research.

The recommendations were published in “Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting,” in the journal Blood Reviews.

AIHAs are a group of rare genetic disorders in which antibodies of the immune system attack and destroy red blood cells. AIHAs are largely grouped into two categories, warm and cold, depending on the ideal temperature for the autoimmune activity. Cold agglutinin disease (CAD) is the most common type of cold AIHA.

Researchers highlight two major diagnostic tests to diagnose AIHA. These include the Direct Antiglobulin Test (DAT) and Indirect Antiglobulin Test (IAT), both known as variants of the Coombs test. The DAT is used most often to diagnose AIHAs.

In the DAT, a sample of blood is collected from the patient, which is then washed of all components excluding the red blood cells. A protein called globulin is added to the sample, and if clumps form in the blood after, it means there were antibodies bound to the red blood cells, indicative of an AIHA. Different forms of globulin are needed to test for different forms of AIHA.

The drawback to the DAT is that it may lead to false positive or false negative results, hindering a correct diagnosis. However, modifications can be made to the DAT protocol, and additional laboratory tests can help supplement the DAT in a diagnosis of an AIHA.

The Blood Reviews article also outlines a number of potential causes for AIHA that may aid in diagnosis, including other disorders, in particular autoimmune diseases and some forms of cancer, recent blood transfusions or blood cell transplants, and side effects from other treatments. More than 150 different treatments have been associated with the development of AIHAs.

The researchers then focused on the various treatment options, which ultimately depend on the form of AIHA and the severity of symptoms. Some patients may have AIHA, but not present symptoms. The primary motivation for beginning AIHA treatment usually is the appearance of anemia symptoms.

If a patient has warm AIHA, the first line of treatment is always a corticosteroid such as prednisone. Sometimes, Rituxan (rituximab) also is prescribed initially, as it is designed to suppress autoimmune activity. However, it is used more often as a second line treatment if the patient stops responding to prednisone.

The next line of treatment is either is splenectomy, which is the surgical removal of the spleen, or a treatment with another agent designed to suppress autoimmune activity. Options include azathioprine, cyclosporine and mycophenolate. Other additional lines of therapy offered to warm AIHA patients include cyclophosphamide, danazol, or bortezomib. In some cases, a transplant of blood stem cells (called hematopoietic stem cells) has been administered for AIHA, but very little evidence supports the success of this technique in treating AIHA.

The line of treatment for cold AIHAs like CAD differs from the warm AIHAs. Rituxan is the most well-documented treatment for CAD patients, though recent evidence indicates that Rituxan in combination with the anti-cancer chemotherapy drug Treanda (bendamustine) has shown promising results in recent clinical studies.

There also are some ongoing clinical trials investigating the effectiveness of certain treatments that would bind to the red blood cells and prevent them from being attacked. Soliris (eculizumab) is an example of one treatment of this sort, and it is being investigated in CAD patients.

Due to the ongoing trials, the researchers cautiously advised that new information about therapies could replace what is contained in their article. “Future recommendations should be based on prospective clinical trials whenever possible,” they wrote.

The article further outlines treatment options for patients with more rare forms of AIHA, as well as emergency treatments and long-term supportive care options that focus on promoting red blood cell creation and managing symptoms.

Also outlined are various factors that are helpful in determining a patient’s long-term outlook. Thrombosis (the formation of clots that block blood vessels) is one such factor.

The researchers concluded that AIHA is very multi-faceted, and treating the disorder ultimately requires a coordinated effort. “We identified a need to establish an international AIHA network,” researchers wrote. Fortunately, an International Consensus Meeting is a good start.