Background: Haemolytic disease of the fetus and newborn (HDFN) is usually associated with IgG alloantibodies, which are active at body temperature, with cold-acting alloantibodies being rarely reported.
Case: A B Rh(D)positive child presented in 2014 at 2 weeks of age with severe haemolytic anaemia (haemoglobin 41g/L) and room temperature (RT) red cell agglutination. She was born following an uncomplicated pregnancy at 39 weeks to a B Rh(D)negative mother, although a weak (titre of 1:2), maternal anti-M had been detected. The direct antiglobulin test was negative, but the maternal anti-M was found, only active at RT. The neonate was transferred elsewhere and diagnosed with paroxysmal cold haemoglobinuria. She improved with phototherapy, M-negative blood transfusions and intravenous immunoglobulin.
During the subsequent pregnancy three years later the anti-M titre was monitored, reaching a titre of 1:16 at 36 weeks. Maternal blood demonstrated an antibody detectible at 4°C, 22°C and 30°C against both adult and cord M+, but not M- cells and not at 37°C (using saline method).
An O Rh(D)positive female was born at 39 weeks via caesarean section. She had a haemoglobin of 167g/L and cold red cell agglutination on her blood film at 6 hours of age. The direct antiglobulin test was positive with Anti-M and Anti-D being eluted from cord cells (the latter weak (2/4), attributed to prophylactic Anti-D given during pregnancy). Haemolysis ensued, requiring phototherapy and transfusions until day 45. Anaemia and agglutination resolved.
Discussion: Allo-antibodies are usually IgG, thus cross the placenta and are active at 37°C, whereas cold agglutinins are usually IgM autoantibodies and as they don’t readily enter fetal circulation, are rarely significant for neonates. This case demonstrates a unique low thermal range allo-anti-M that crossed the placenta to cause HDFN, but only post-delivery as the antibody had minimal activity at 37°C, but activity at RT. Anti-M antibodies are frequent in pregnancy and are of variable significance not predicted by titres.