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Forum Name: Hematology Topics

Question: cold agglutinin disease- need specialist


 purple - Sun Nov 13, 2005 2:38 am

I have cold agglutinin disease with an unknown cause- titier 1:4096. Have tried Rituxan twice. Nobody knows what to do next. Any advice or specialists, anywhere in the country, with expertice in this area would be appreciated! I'm looking for someone that has treated many cases. I know this is rare and most doctors have not treated this.
 Dr. Safaa Mahmoud - Wed Jul 26, 2006 1:55 pm

User avatar Dear purple,

Cold agglutinins (capable of agglutinating RBCs) are immunoglobulin M (IgM) antibodies in the majority of cases, (less common [IgA] or [IgG]). These antibodies can result in RBC agglutination and destruction in the reticuloendothelial system (hemolytic anemia). Slowing of blood flow into the peripheral vessels results in a Raynaud like syndrome (acrocyanosis). Hemagglutination occurs mainly at 4°C and not at 37°C, hence the name cold agglutinins.

On exposure to cold, painful fingers and toes with purplish discoloration of the peripheral parts of the body including ears, nose, forehead and digits take place.
Classic chronic CAD is idiopathic, of unknown cause and symptoms occur on cold exposure with diverse degrees of severity.

Lymphoproliferative (includingB cell lymphomas), myeloma and autoimmune diseases may be associated with the production of IgM cold agglutinin.

Many blood tests are done to diagnose cold aggluitinination of RBCs. Specific tests include, the Direct Comb's test (DAT, direct antiglobulin test)

• In general treatment of the idiopathic form of the disease is conservative with protection from cold exposure, correction of any other aggrevating facors like anemia. The disease is of benign course showing periods of spontaneous exacerbation's and remissions.

Steroids are not very effective and may mask the diagnosis of an associated lymphoproliferative. Prednisone appears to be effective in cases with low cold agglutinin titer, and high thermal amplitude. Plasma pharesis is considered by some doctors in severe cases when other measures fail to induce remission of the symptoms but causes temporary relief.
Chemotherapy is generally avoided in the treatment of idiopathic Cold agglutination disease CAD. Benefits versus the long term effects of these agents should be considered while describing any of the chemotherapeutic agents. Chlorambucil has been used successfully in CAD.
• Patients with lymphomas and cold agglutinins are known to have a more chronic course. In such cases treatment of the underlying lymphoma with Cyclophosphamide, vincristine and fludarabine were all successful. In patients who fails on these different chemotheraputic regimens, rituxan has been effective in treating symptoms due to the cold agglutinins and refractory autoimmune hemolytic anemia.

I hope you find this infromation useful.
Best regards,

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