The hallmark feature is the formation of polyclonal IgG autoantibody against the P antigen, which is a polysaccharide surface antigen on red cells in most humans. As a weak, biphasic antibody, it absorbs to the P antigen in the cold temperature as in the periphery in the primary phase, and fixes complement on recirculation to the core temperature in the secondary phase, resulting in intravascular hemolysis. Diagnosis
The purposes of laboratory investigations are to: 

Confirm the presence of intravascular hemolysis in terms of metabolic products of red cells and hematopoietic response. Establish the diagnosis of autoimmune hemolytic anemia and differentiate from other AIHA. Identify other supporting features as in hematopathological findings.For intravascular hemolysis, the laboratory parameters include increased serum free hemoglobin, lactate dehydrogenase, unconjugated bilirubin, and reduced haptoglobin. Urine tests may show elevated hemoglobinuria and hemosiderinuria in chronic cases. Reticulocytosis may not be apparent in the acute phase or when there is viral-induced myelosuppression.Once the clinical suspicion of autoimmune hemolytic anemia is made, direct antiglobulin test (DAT) or direct Coombs test is the first line of investigation to confirm the presence of warm autoantibodies. Testing with polyspecific and IgG-specific antiglobulin agents is usually negative, and that with C3-specific agent may be positive. On excluding warm autoimmune hemolytic anemia (WAIHA), the cold agglutinin titer should be examined for cold agglutinin disease (CAD). The diagnosis of PCH is suspected when both WAIHA and CAD are excluded. The complement level is usually low. Donath-Landsteiner test is the confirmatory test for PCH.
Supportive treatment includes rest, normothermia and transfusion when indicated. Intensive care for the development of acute kidney injury should be offered. Plasmapheresis is proposed to be an adjunctive measure to facilitate recovery. Steroids and other immunosuppressants are sometimes administered and the beneficial effect is uncertain. Immunotherapy is considered in refractory to corticosteroids and immunosuppression. Monoclonal antibodies e.g. rituximab (anti-CD20) and eculizumab (anti-C5) have been used but the therapeutic benefits are controversial. Antibiotic therapy should be given if syphilitic cause is confirmed, while investigations and management for hematological malignancies should be pursued in adult patients with unexplained PCH. Epidemiology
Estimated incidence of PCH is 0.4 per 100000 population, and the prevalence ranges from 1.6% to 40% in patients with autoimmune hemolytic anemia. The prevalence depends on the sensitivity of the immunologic methods applied. The age of onset is often <5 years in the pediatric population, with male predominance ranging from 2.5:1 to 5:1 in male-to-female ratio.The majority of PCH were accounted by congenital or tertiary syphilis in the early 1900s. Since the application of antibiotic therapy and prenatal screening, syphilitic PCH has become a rare entity. It is now increasingly recognized in pediatric patients with preceding viral-like illness. See also
Cold agglutinin disease
Cold sensitive antibody
Hemolytic anemia
List of hematologic conditions

References


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