Paroxysmal cold hemoglobinuria: a difficult diagnosis in adult patients

Abstract

Positive DL test results are rare and occur more commonly in children than adults. There was poor agreement among experts on the interpretation of a positive DL test in adults. These observations highlight the difficulties in establishing the diagnosis of PCH in adults and calls for scrutiny of current laboratory practice.

Case of Donath-Landsteiner haemolytic anaemia in an adult female

“…DLHA is a haemolytic anaemia caused by the presence of the D-L antibody, a specific cold-reacting immunoglobulin against the P or I antigen on the red blood cell surface 1. DLHA can either be idiopathic or secondary to infections, autoimmune conditions or malignancy.…”

“…D-L antibody is a biphasic IgG antibody that binds to the P antigen in the cold by fixing the early components of complement and causes complement mediated haemolysis as the temperature increases to 37°C. The antibody dissociates from the RBC’s at 37°C but the complement mediated haemolysis continues 1. In the D-L test, the patient’s serum is cooled down to 4°C to allow fixing of complement to the P antigen, followed by warming of the sample to 37°C.…”

“…In her case normal human serum was used as the source of complement and the test result came out positive making the diagnosis of DLHA or PCH. The patient was transfused with packed red blood cells (pRBCs) prior to D-L testing but some data from case series show that it does not seem to impact the results of D-L testing 1. Syphilis testing was negative.…”

Microangiopathy and acute kidney injury in paroxysmal cold hemoglobinuria: A challenge for management

“…PCH is a rare cause of autoimmune hemolytic anemia in adults, but may be the most common cause in children . PCH is caused by an antibody hemolysin that binds the P1 antigen on erythrocytes at low temperature, then triggers complement activation on rewarming to 37 ° C. 2 This is the basis of the Donath‐Landsteiner test: patient serum does not hemolyse reagent red cells at 37 ° C unless the mixture has already been incubated at 0 ° C. PCH in children is usually attributed to antecedent viral illness .…”

“…In adults this may be the case, but was historically related to secondary and tertiary syphilis . Other causes include malignancy and autoimmune disease . Presentation is with features of severe intravascular hemolysis—fever, rigors, jaundice, hemoglobinuria, and pallor.…”