Table 1.

Cold-antibody mediated autoimmune hemolytic anemias.

Entity	Etiology	Autoantibody properties	Ig class	Complement activation	Predominant type of hemolysis	Incidence
Cold agglutinin disease (CAD)	Primary (low-grade LPD)	Cold agglutinins, anti-I (rarely anti-Pr or anti-IH)	IgM	Classical pathway ++, terminal pathway (+)	Extravascular	Uncommon, mainly elderly people
Cold agglutinin syndrome (CAS)	Secondary (Mycoplasma, EBV; aggressive lymphoma)	Cold agglutinins, anti-I or anti-i (rarely anti-IH?)	IgM or IgG	Classical pathway ++, terminal pathway (+)	Extravascular	Rare, any age
Paroxysmal cold hemoglobin-uria (PCH)	Children: Mostly postviral. Adults: Tertiary syphilis or hematologic malignancy.	Non-agglutinating biphasic Ab, anti-P	IgG	Classical pathway +++, terminal pathway +++	Intravascular	Rare in children, ultra-rare in adults

Ab, antibody; EBV, Epstein-Barr virus; Ig, immunoglobulin; LPD, lymphoproliferative disorder.

Based on data from Sokol et al. (1), Berentsen and Tjønnfjord (2), Jäger et al. (3), Barcellini et al. (4), Randen et al. (5), and Shanbhag and Spivak (6).