Donath Landsteiner Antibody

Paroxysmal cold hemoglobinuria (PCH) is a rare form of autoimmune hemolytic anemia. It was characteristically associated with syphilis in the past, but nowadays is more often associated with acute viral infections. PCH accounts for up to 40% of autoimmune hemolytic anemia cases in younger children. Most childhood cases have a clear history of a previous upper respiratory infection.

PCH is often transient, but intravascular hemolysis can be severe in the acute phase. Blood transfusion may be required in some cases. It is not necessary to transfuse P antigen-negative red blood cells. Donor units of red blood cells do not need to be washed to remove residual complement. In life-threatening disease, plasma exchange may temporarily reduce hemolysis. Steroid therapy should be reserved for severe or persistent disease.

Patients usually have a positive direct antiglobulin test (DAT) with C3d. The autoantibody that causes this syndrome is called the Donath Landsteiner antibody.  It is also referred to as a biphasic cold hemolysin, because it binds to red blood cells only at cold temperatures and causes complement mediated hemolysis only after warming to body temperature. The autoantibody often has specificity for the P blood group antigen.

The Donath Landsteiner test is performed by drawing two tubes of blood. One is immediately incubated at 37^o C for one hour. The second tube is immediately incubated in an ice bath for 30 minutes and then transferred to a 37^o C water bath for an additional 30 minutes. Both tubes are then centrifuged and examined for hemolysis. If the serum of the tube incubated in the cold is hemoglobin-tinged and the serum of the tube that remained at 37^o C is clear, the patient has a Donath Landsteiner antibody. If both the cold and warm incubated tubes are hemolyzed, no conclusion can be drawn about the presence of a Donath Landsteiner antibody.  

If one tube of blood is not strictly maintained at 37°C from collection through testing, anti-P antibodies may autoadsorb onto autologous red blood cells and give a falsely negative test result.  False positive results may occur if the patient has a cold autoantibody.

Reference value is a negative result. 

Specimen requirement is two 4-mL pediatric red top tubes immediately incubated in an ice bath and a 37^o C water bath.

References

Hill QA et al. The diagnosis and management of primary autoimmune haemolytic anemia, Brit J Haematol, 2017;176:395-411.

Parker V, Tormey CA. The Direct Antiglobulin Test: Indications, Interpretation, and Pitfalls, Arch Pathology Lab Med, 2017;141:305-310.