Two Case Studies and A Review of Paroxysmal Cold Hemoglobinuria

Red blood cell (RBC) autoantibodies are a relatively uncommon cause of anemia. However, autoimmune hemolytic anemia (AIHA) must be considered in the differential diagnosis of hemolytic anemias, especially if the patient has a concomitant lymphoproliferative disorder, autoimmune disease, or viral or mycoplasmal infection. Classifications of AIHA include warm AIHA, cold agglutinin syndrome, paroxysmal cold hemoglobinuria, mixed-type AIHA, and drug-induced AIHA. Characteristics of the autoantibodies are responsible for the various clinical entities. As a result, diagnosis is based on the clinical presentation and a serologic work-up. For each classification of AIHA, this review discusses the demographics, etiology, clinical presentation, laboratory evaluation, and treatment options. Copyright 2002 Wiley-Liss, Inc.

The cold antibody autoimmune hemolytic anemias (AIHAs) are primarily comprised of cold agglutinin syndrome (CAS) and paroxysmal cold hemoglobinuria (PCH) but, in addition, there are unusual instances in which patients satisfy the serologic criteria of both warm antibody AIHA and CAS ("mixed AIHA"). CAS characteristically occurs in middle-aged or elderly persons, often with signs and symptoms exacerbated by cold. The responsible antibody is of the IgM immunoglobulin class, is maximally reactive in the cold but with reactivity up to at least 30 degrees C. Therapy is often ineffective, but newer agents such as rituximab have been beneficial in some patients. PCH occurs primarily in children, often after an upper respiratory infection. The causative antibody is of the IgG immunoglobulin class and is a biphasic hemolysin that is demonstrated by incubation in the cold followed by incubation at 37 degrees C in the presence of complement. Acute attacks are frequently severe but the illness characteristically resolves spontaneously within a few days to several weeks after onset and rarely recurs. Treatment consists of supportive care, with transfusions frequently being needed.

Over eighty years have passed since Donath and Landsteiner identified the syndrome of PCH and reported an in vitro test for its diagnosis. The accuracy of their observations, and the usefulness of the DL procedure has persisted. PCH has been investigated over the years providing further information regarding antibody specificity and serological characteristics. However, the etiology of the syndrome remains to be elucidated. PCH, which was once thought to be rare and associated primarily with congenital syphilis, is not encountered as one of the most common causes of acute transient hemolytic anemia in young children.