A Case of Paroxysmal Cold Hemoglobinuria Possessing Moderate Paroxysmal Nocturnal Hemoglobinuria-Type Erythrocytes

Abstract

BACKGROUND Paroxysmal cold hemoglobinuria (PCH) is an autoimmune hemolytic disease caused by the Donath-Landsteiner (DL) antibody. Paroxysmal nocturnal hemoglobinuria (PNH) is a non-autoimmune hemolytic disease that is caused by a dysfunction in the synthesis of the glycosyl phosphatidylinositol anchor protein, resulting in the deregulation of the complement cascade and hypersensitivity for a hemolytic attack against erythrocytes. The mechanisms of these 2 hemolytic diseases are distinct. If PCH and PNH coexist in a patient, it is difficult to perform a differential diagnosis. We introduce a case of PCH that had DL antibodies and large PNH-type clones. CASE REPORT An 82-year-old female patient was referred to our hospital because of anemia. Initial workup revealed a negative antiglobulin test and a positive DL test. For the differential diagnosis, we surveyed the population of cells that had PNH-type clones, which revealed erythrocyte PNH clones (19.6%) and granulocyte PNH clones (73.3%). During the patient's clinical course, mild hemolysis persisted without any attack. The percentage of the PNH-type erythrocytes was not obviously changed, and the DL antibody was detected 8 months after the initial admission. We determined that the persistent mild anemia was caused by concomitant diseases of PCH and PNH, although determining which of the 2 hemolytic systems was primarily responsible for the anemia was difficult. CONCLUSIONS When considering the differential diagnosis for hemolytic diseases, an adequate combination of laboratory tests for hemolysis is required.

Figure 1.

(A) The bone marrow findings from the bone marrow aspiration (×600, hematoxylin and eosin staining). Erythroid hyperplasia with megaloblastic change was observed. (B) Erythrocyte paroxysmal nocturnal hemoglobinuria (PNH) clones. Erythrocyte PNH clones are expressed as the total of Type II (partial deficiency) and Type III (complete deficiency) clones. (C) Granulocyte PNH clones. Granulocyte PNH clones are expressed as the total of Type II (partial deficiency) and Type III (complete deficiency) clones.

Figure 2.

Clinical course. The population of erythrocyte and granulocyte paroxysmal nocturnal hemoglobinuria (PNH) clones is presented by percentage. DAT – direct antiglobulin test; DL test – Donath-Landsteiner test; Hb – hemoglobin; LD – lactate dehydrogenase; RBC – transfusion of red blood cells