Paroxysmal cold hemoglobinuria due to an IgA Donath–Landsteiner antibody

Abstract

Paroxysmal cold hemoglobinuria (PCH) is an autoimmune hemolytic anemia (AIHA) characterized by the presence of a Donath-Landsteiner (D-L) antibody. PCH occurs most commonly in young children and is associated with acute, often self-limited hemolytic anemia. The D-L antibody is classically a biphasic IgG anti-P autoantibody identified by the D-L test. Rare case reports confirm the existence of IgM D-L antibodies. We report the case of a 2-year-old male diagnosed with acute AIHA and found to have PCH caused by an IgA D-L antibody. The clinical course and treatment of this condition, which has not been reported previously, are described.

Kids, colds, and complement: paroxysmal cold hemoglobinuria

“…It should also be noted that both PCH episodes were accompanied by reticulocytopenia during the first 2 to 4 days . Severe anemia with a low or normal reticulocyte count has been documented in many PCH cases . In one study, a third of children (8/25) less than 6 years of age had low or normal reticulocyte counts despite a mean Hb level of 6.3 g/dL (range, 4‐9 g/dL) .…”

“…A more recent article demonstrated direct binding of PCH serum to purified globoside and RBC neutral GSLs by thin‐layer chromatography . Although anti‐P IgG is the most common antibody encountered in PCH, there are PCH cases with biphasic IgM and IgA antibodies, and other carbohydrate specificities (I, i, HI, Pr) …”

“…Despite recent infection, PCH is not associated with an increase in cold agglutinin titers . Peripheral blood findings include spherocytosis and autoagglutination or rouleaux in 50% and 17% to 25% of cases, respectively . RBC‐neutrophil rosettes and erythrophagocytosis by neutrophils, which are usually cited as pathognomonic findings for PCH, are encountered infrequently (9%) …”

“…In both episodes, the patient had a prior URI, followed by hemolysis a few weeks later. While many laboratories (including my own) confine DL testing to P+ RBCs, the authors performed the DL test with a five‐cell panel that included I– and P– (p) RBCs. In both episodes, they were able to demonstrate an autoanti‐P.…”

Donath-Landsteiner test

“…Some case reports, however, show these antibodies having IgM and IgA class specificities. 6,7 Initially, at cold temperatures, the antibodies bind to RBCs, causing complement (C3) to irreversibly bind to the RBCs at the same time. As this complex is warmed to 37°C, activation of the complement cascade leads to intravascular hemolysis of RBCs when the autoantibody dissociates.…”