Cold Agglutinin Disease

Cold Agglutinin disease (CAD or CHAD) is a haematological disorder where the body produces an abnormal Immunoglobulin M which binds to red cells. In cold conditions - sometimes the peripheries are cold enough - this antibody causes red cells to clump and this can cause local vascular occlusion. CAD causes a number of problems for the laboratory. Although patients are often anaemic, they can mistakenly be registered by laboratory equipment as much more anaemic than they really are as the clupmed red cells can be ignored in the Haemoglobin/red cell calculation. CAD also causes problems for blood grouping - the forward group relies on the ability of crosslinking IgM to detect A and B sugars on red cells, however in the presence of a non-specific IgM binder everything reads positive, so it isn't possible to get an accurate forward group. The solution here is to process the group at strict 37.

On a blood film, which is usually procesed at room temperature, you see the appearance here - lots of clumped red cells and often a blue background hue. 

CAD is associated with a number of significant medical issues - including lymphoproliferative disorders, mycoplasma pneumonia or EBV infection. Treatment depends on the cause - if there is an identified cause, this is a secondary CAD and the treatment is to treat the underlying condition, or to support and manage conservatively until improved. Primary CAD can be managed by intermittent transfusion support or anti-B cell therapy such as Rituximab. Plasma echange can be used - but the IgM is often very high titre and so efficacy is uncertain.

Remember if you are giving blood...use a warmer, or the blood you give will clump as well. It's not a red cell problem, it's a plasma problem.