Paroxysmal cold hemoglobinuria requiring differentiation from thrombotic microangiopathy

Abstract

Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia triggered due to complement activation by Donath–Landsteiner (DL) antibodies, causing intravascular hemolysis. PCH generally occurs after an infection in children. It is transient and has a good prognosis, but it may result in acute kidney injury in severe cases. A 5-year-old girl developed fever, vomiting, and red-colored urine a few days after onset of common cold symptoms, suggesting nephritis. Subsequently, she developed jaundice, hemolytic anemia, increased inflammatory response, abnormal coagulation, hematuria, and proteinuria. Additionally, mild renal dysfunction was observed, and thus, thrombotic microangiopathy (TMA) was suspected. Her direct Coombs and DL tests yielded positive results, and the results of other tests ruled out TMA. Thus, she was diagnosed with PCH. Subsequently, she was treated conservatively and recovered by avoiding cold stimulation. Three months after the onset, DL antibodies were negative. In conclusion, severe intravascular hemolysis caused by PCH can lead to thrombosis; therefore, differentiation from TMA is crucial.