Paroxysmal cold hemoglobinuria (PCH)

Rare form of autoimmune hemolytic disorder in adults with massive hemolysis following cold exposure.

Related process more common seen in children or young adults associated with acute but self-limited hemolysis following several viral syndromes.

Donath-Landsteiner cold reactive autoantibody responsible for complement mediated hemolysis.

The Donath-Landsteiner antibody binds to its antigen at temperatures below essential body temperature, but activation of the classical complement pathway occurs after warming to 37°C in the central circulation: The terminal complement cascade is activated and hemolysis that occurs is predominantly intravascular.

Serum antibody demonstrated by the biphasic Donath-Landsteiner hemolysis test and is almost always an anti-P autoantibody.

Associated with congenital and tertiary syphilis and is therefore less common today.

During chilling induced by infectious agents the Donath-Landsteiner antibody and early acting complement components bind to red blood cells in blood flowing through skin capillaries and then when cells reenter the central circulation lysis of cells occur by the terminal complement sequence.

Donath-Landsteiner antibody dissociates from RBC’s at 37º C but prior to that it initiates the complement pathway.

Constitutes 2-5% of autoimmune hemolytic anemias.

Among children account for about 32% of cases of immune hemolytic anemia.

It is a rare disease that occurs almost exclusively contemporarily as a post viral complication in children.

No racial or genetic risk factors.

During hemolysis, a few minutes to several hours after exposure to cold patients present with aching back, legs, abdominal cramping, and headaches followed by chills and fever.

During hemolytic episode hemoglobinuria may occur and last a few hours.

Raynaud’s phenomena and cold urticaria may occur as may delayed jaundice.

Hemoglobinuria seen early during the attack causing dark, red or brown urine due to the presence of hemoglobin or methemoglobin.

Hemoglobin levels often fall rapidly during an acute severe attack.

Laboratory changes include reticulocytosis, hemoglobinemia, and hyperbilirubinemia.

Serum complement levels are usually decreased during an acute attack reflecting rapid consumption.

Spherocytosis and erythrophagocytosis may occur and be seen on blood smears.

Leukopenia and leucocytosis may be seen in the early and late phases, respectively.

Direct antiglobulin test is usually positive during and shortly after the acute process as a result of red blood cell coating with C3d complement fragments.

Donath-Landsteiner antibody is a nonagglutinating IgG that binds to red blood cells during cold and readily unbinds during room temperature.

Antibody is detected when the patient’s serum is incubated with RBC’s initially at 4ºC and mixture warmed to 37ºC with intense hemolysis indicated.

Donath-Landsteiner antibody has specificity for the P blood group antigen.

Donath-Landsteiner titers rarely exceed 1:16.

Must be distinguished from chronic cold agglutinin disease which is manifested by episodic hemoglobinuria and hemolysis.

Patients with cold agglutinin disease usually have much higher titers of cold agglutinins.

Most cases self-limited and can be prevented by avoiding exposure to cold.

Steroids and splenectomy are not useful treatments.

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