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Paroxysmal cold hemoglobinuria

Author
Carlo Brugnara, MD
Section Editor
Stanley L Schrier, MD
Deputy Editor
Jennifer S Tirnauer, MD

INTRODUCTION

Paroxysmal cold hemoglobinuria (PCH) was one of the first hematologic syndromes to be recognized clinically. The association between red to brown urine (quickly recognized as hemoglobinuria) being passed following exposure to cold was established by 1872. The recognition that this syndrome was often seen in patients with syphilis soon followed and the demonstration of an antibody as the cause came in 1904, from the studies of Donath and Landsteiner [1].

This topic review will discuss the major features of PCH. The more common cold agglutinin syndromes are discussed separately. (See "Pathogenesis of autoimmune hemolytic anemia: Cold agglutinin disease" and "Cold agglutinin disease".)

PATHOPHYSIOLOGY

The antibody in PCH is a cold-reacting IgG. It is always polyclonal. Unlike cold-reacting IgM, it does not cause red cell agglutination but, similar to cold-reacting IgM, it is able to fix complement readily. The maximum temperature at which these antibodies are able to interact (ie, their thermal amplitude) varies greatly from patient to patient, as is also the case with the IgM cold agglutinins.

The mechanism of hemolysis in PCH is similar to that in cold agglutinin disease. As the blood circulates to the periphery, it cools, and the antibody and the first two components of complement are fixed to the RBC surface. The complement cascade is completed only when the RBC are subsequently warmed to 37°C. For reasons that are not clearly understood, perhaps because the antigen is located on the RBC membrane surface, these antibodies are quite efficient in bringing about direct lysis by complement; this results in intravascular hemolysis, hemoglobinuria, and hemosiderinuria. (See 'Antibody specificity' below and "Diagnosis of hemolytic anemia in the adult", section on 'Intravascular hemolysis'.)

Antibody specificity — The antigen with which the antibody in PCH interacts is the P antigen, a polysaccharide that is usually affixed to a ceramide moiety on the surface of the red cell [2]. This antibody will cause hemolysis in almost all subjects, since only rare individuals have red cells lacking the P antigen (the pp or Tj(a) - phenotype). Of interest, the P antigen structure is also a binding site for parvovirus, one strain of which (B19) causes transient pure red aplasia [3]. (See "Clinical manifestations and diagnosis of parvovirus B19 infection" and "Red blood cell antigens and antibodies", section on 'Lewis, P1P(K), GLOB, and I blood group systems'.)

              

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Literature review current through: Nov 2016. | This topic last updated: Wed Nov 04 00:00:00 GMT+00:00 2015.
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References
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