How to use Donath-Landsteiner test to diagnose paroxysmal cold haemoglobinuria (PCH)

Abstract

Paroxysmal cold haemoglobinuria (PCH) accounts for around a third of cases of autoimmune haemolytic anaemia in children. PCH is caused by an autoantibody that fixes complement to red cells at low temperatures and dissociates at warmer temperatures (a biphasic haemolysin), triggering complement-mediated intravascular haemolysis. Named the Donath-Landsteiner (D-L) antibody after its discoverers, it is usually formed in response to infection and demonstrates specificity for the ubiquitous red cell P-antigen. A D-L test can be used to detect the presence of the D-L autoantibody in the patients’ serum. Here we discuss the use of the D-L test in identifying PCH in a 2-year-old boy who presented with haemolytic anaemia. A summary of the key information can be found in the infographic.

A Case of Childhood Severe Paroxysmal Cold Hemoglobinuria with Acute Renal Failure Successfully Treated with Plasma Exchange and Eculizumab

“…e classic presentation of childhood PCH consists of pallor, jaundice, fevers, and hemoglobinuria [4,5]. Other symptoms can include abdominal pain, nausea, anorexia, myalgias, cough, confusion, and fatigue [2][3][4]. Our patient exhibited nearly all of these symptoms on initial presentation.…”

“…We present a child with hemolytic anemia and multiorgan dysfunction, ultimately diagnosed with PCH. Diagnosis can be delayed due to its ability to mimic numerous other processes and the di culty of obtaining con rmatory laboratory testing [1,2].…”

“…is disease process is typically self-resolving and rarely associated with severe renal injury requiring dialysis [1][2][3][4][5][6]7].…”

Neutrophilic erythrophagocytosis in a child with paroxysmal cold hamoglobinuria

“…This specialized test is performed in reference laboratories in the United Kingdom. The D‐L antibody is a biphasic, usually IgG antibody, that binds with the “P” antigen on red cells at low temperature and causes complement‐mediated lysis in red cells coated with C3 on rewarming [3]. Difficulty in maintaining the correct temperature during sample collection and handling will lead to a falsely negative result [3], and it is the most likely reason for this result in this case.…”

“…The D‐L antibody is a biphasic, usually IgG antibody, that binds with the “P” antigen on red cells at low temperature and causes complement‐mediated lysis in red cells coated with C3 on rewarming [3]. Difficulty in maintaining the correct temperature during sample collection and handling will lead to a falsely negative result [3], and it is the most likely reason for this result in this case. A negative D‐L antibody test should not dissuade the clinician from a diagnosis of PCH when the clinical features and other tests are otherwise supportive.…”