A three-year-old female child presented at the casualty department. She had been unwell with tonsillitis for the past week. A full blood count revealed the following results:
Hb 67 g/L, WBC 24.2 x 109/L and platelets 452 x 109/L.
The blood film was leucoerythroblastic with a reticulocytosis and a moderate number of spherocytes. There was an absolute neutrophilia of 14.0 x 109/L. A preliminary diagnosis of autoimmune haemolysis was made. A direct antiglobulin test (DAT) was performed with a positive result. The LDH was raised at 666 IU/L demonstrating acute haemolysis. Urinalysis revealed dark brown urine with a small number of red cells.
As this was an acute presentation (the child was well two weeks previously) the possibility of paroxysmal cold haemoglobinuria (PCH) was considered. A Donath-Landsteiner test was performed and the result was positive.
PCH is a disease characterised by the sudden presence of haemoglobin in the urine after exposure to cold temperatures. It occurs mostly in young children under the age of five years. There is a male to female ratio of 2:1 to 5:1.
In 1904 Julius Donath and Karl Landsteiner described an autoimmune haemolytic anaemia characterised by the presence of a biphasic antibody that attaches to red cells in the cold inducing haemolysis when the red cells are subsequently warmed. The Donath- Landsteiner (D-L) antibody is a polyclonal IgG binding to various red cell antigens such as I, i, p and P on the red cell surface. The P antigen is its primary target. This polyclonal IgG anti-P autoantibody binds to red blood cell surface antigens in the cold. When the blood returns to the warmer central circulation, the red cells are lysed with complement, causing intravascular haemolysis. The attachment of C3d on the red cells results in a positive DAT. The resultant blood picture is that of a normochromic normocytic anaemia with spherocytes, reticulocytes, especially in the recovery phase, auto agglutination and nucleated red cells. Monocytes and granulocytes sometimes show erythrophagocytosis.
The Donath-Landsteiner (D-L) antibody test is performed as follows:
The method involves preparing three tubes: 1) the patient’s serum, 2) a mixture of patient’s serum and normal serum and 3) normal serum. To each tube is added P-positive red cells at 4℃. After 30 minutes the tubes are then heated to 37℃ and observed visually for haemolysis, indicative of a positive result.
PCH is associated with upper respiratory and gastrointestinal symptoms. It may occur following measles, mumps, influenza, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, adenovirus, parvovirus B19, Coxsackie A9, Haemophilus influenzae, Mycoplasma pneumoniae and Klebsiella pneumoniae. It also may occur post vaccination for measles.
PCH is a self-limiting disease. If promptly diagnosed and appropriately treated with supportive care, most patients recover within days to a few weeks. Supportive treatment may include pre-warmed packed red blood cells as well as steroids although steroids have not been shown to shorten the course of the disease.
The patient in this case study was transfused warm packed red blood cells. She remains well.