Paroxysmal cold hemoglobinuria (PCH) is an autoimmune hemolytic anemia featured by complement-mediated intravascular hemolysis after cold exposure. It can present as an acute non-recurrent postinfectious event in children, or chronic relapsing episodes in adults with hematological malignancies or tertiary syphilis. Described by Julius Donath (1870–1950) and Karl Landsteiner (1868–1943) in 1904, PCH is one of the first clinical entities recognized as an autoimmune disorder. Signs and symptoms
Pediatric patients usually present with acute onset of hemolytic anemia with fatigue, exercise intolerance, pallor, jaundice, and hemoglobinuria, preceded by exposure to cold temperature and preceding viral-like illness. This may be complicated by acute renal failure due to nephrotoxic free hemoglobin and tubular obstruction. Although the disease may be fulminant during onset, the acute form generally follows a transient, self-limiting course.Chronic relapsing PCH manifests as episodic hemoglobinuria and anemic symptoms, usually milder than the acute form. While the classical syphilitic PCH becomes infrequent, paraneoplastic cause with underlying hematological malignancies especially in the elderly should be considered. Hepatosplenomegaly and adenomegaly are not pertinent to PCH, unless associated with underlying lymphoproliferative disorders. This form remains refractory if the underlying condition is not treated. Cause
Infectious agents are implicated in the acute form of PCH. Viral agents include measles, mumps, Epstein-Barr virus, cytomegalovirus, varicella-zoster virus, influenza virus, and adenovirus. Non-viral agents include Mycoplasma pneumoniae and Haemophilus influenzae. Chronic relapsing PCH is classically associated with syphilis, as well as hematological malignancies including non-Hodgkin lymphoma and myeloproliferative neoplasms. Pathophysiology
The exact pathogenesis is not fully elucidated.
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.