T activation is the most common acquired polyagglutination, especially in children and infants. It is caused by removal of portions of glycophorin A and B chains on the surface of the red blood cell with exposure of “cryptantigens.” The cryptantigens render the cells more susceptible to agglutination by normal human plasma (which contains naturally occurring antibodies against the cryptantigens). Streptococcus pneumoniae, Clostridium perfringens, and Vibrio cholerae are most commonly involved (as well as the influenza virus). Most T activation is benign, causing occasional problems in the laboratory when typing or crossmatching, but numerous case reports of hemolysis after plasma transfusions to these patients exist. As a result, if a patient is diagnosed with T activation, they will usually receive only washed RBC and platelet products, and plasma transfusion is avoided when possible. T activation is separated from other forms of polyagglutination (such as Tn polyagglutination) in the laboratory through characteristic reactions with a panel of lectins.