A 4-year-old boy presented with fever and chills for 3 days, and history of passing red urine. On examination, the child was pale, but had no icterus or lymphadenopathy. Liver and spleen were enlarged 3 cm and 2 cm, respectively below the costal margin. Initial investigations showed hemoglobin of 8 g/dL, total leukocyte count of 20.4×109 /L and platelet count of 160×109 /L. He was empirically treated with ceftriaxone and artesunate. Peripheral smear for malarial parasite, and cultures of blood and urine were sterile. On day 2 of admission, his hemoglobin dropped to 5 g/dL and creatinine increased from 0.5 mg/dL to 1.3 mg/dL. There was no evidence of bleeding from any site. Serum bilirubin was 2.7 mg/dL with an indirect component of 1.7 mg/dL. Aspartate transaminase (AST) was 187 U/L and alanine transaminase (ALT), 27 U/L. Peripheral smear demonstrated nucleated RBCs and micro-spherocytes with a reticulocyte count of 4.3%. Lactate dehydrogenase (LDH) was 3474 IU/L and urine for hemoglobin was positive. Direct Coombs test, glucose-6-phosphate dehydrogenase, high pressure liquid chromatography and anti-nuclear antibodies were negative. Hemoglobin continued to drop despite blood transfusions. He was treated with oral prednisolone (2 mg/kg/day) considering possibility of Coombs negative autoimmune hemolytic anemia. Child had normal serum ceruloplasmin and negative flow cytometric analysis for paroxysmal nocturnal hemoglobinuria. Complement C3 was normal and C4 was low (<5 mg/dL). Further evaluation for hemolysis revealed a positive Donath Landsteiner antibody. Child was diagnosed as having paroxysmal cold hemoglobinuria (PCH), and prednisolone was stopped. We could not perform tests for Ebstein-Barr virus (EBV) or mycoplasma in this child. Hemoglobin improved spontaneously with improvement in LDH (2690 U/L to1842 U/L) and creatinine (1.3 mg/dL to 0.3 mg/dL). He was discharged 10 days after admission with stable hemoglobin.

Demonstration of anti-P antibody is important for diagnosis. It is recommended to collect 3 aliquots of patient’s blood kept in pre-warmed tubes to prevent hemolysis. The test is considered as positive for Donath Landsteiner antibodies if hemolysis occurs only in the aliquot that was incubated initially at 0-4ºC for 30 min followed by incubation at 37ºC for 60 min.

PCH resolves spontaneously with most patients improving within one month without any specific therapy.　Patient should be kept warm; a blood warmer to be used during transfusion. P-negative blood has been used for transfusions in patients with PCH in whom hemolysis was severe and prolonged; however, its effectiveness is difficult to evaluate because of the unpredictable natural course of the disease. Corticosteroids are often administered to patients; however, the efficacy is not known [6]. Timely recognition of PCH will prevent initiation of unnecessary therapy and help in rapid resolution of hemolysis.

6. Heddle NM. Acute paroxysmal cold hemoglobinuria. Transfus Med Rev. 1989;3:219-29.