[1] It can present as an acute non-recurrent postinfectious event in children, or chronic relapsing episodes in adults with hematological malignancies or tertiary syphilis.
[3][4][5][6] For example, there was a case study reporting that autoimmune hemolytic anemia where an IgA Donath–Landsteiner denoted as [D-L] antibody appeared to cause Donath–Landsteiner cold hemoglobinuria.
[9][10] Chronic relapsing PCH manifests as episodic hemoglobinuria and anemic symptoms, usually milder than the acute form.
[1] While the classical syphilitic PCH becomes infrequent, paraneoplastic cause with underlying hematological malignancies especially in the elderly should be considered.
[citation needed] Signs and symptoms of DHLA is tied to an abrupt onset of hemoglobinuria subsequent to cold exposure.
[3] Exact signs and symptoms of DLHA are anemia-alike[3] (dyspnea, palpitations, fatigue, pallor and hemolysis-alike[3] (jaundice, dark urine and pain).
Some signs and symptoms indicate a medical emergency and that the patients with DLHA require to be hospitalized:[11] Infectious agents are implicated in the acute form of PCH.
Chronic relapsing PCH is classically associated with syphilis, as well as hematological malignancies including non-Hodgkin lymphoma and myeloproliferative neoplasms.
As a weak, biphasic antibody, it adsorbs on to the P antigen in the cold temperature as in the peripheral circulation in the body in the primary phase, and fixes initial components (up to C2) of the classical complement pathway.
Upon recirculation to the core temperature of 37°C in the secondary phase, Anti-P autoantibody dissociates itself from the red blood cell, however, complement components remain bound and rest of the classic complement cascade proceeds till the formation of membrane attack complex (MAC) that disrupts red cell membrane resulting in intravascular hemolysis.
[16] The causative agent of DLHA is a cold-active immunoglobulin commonly denoted as the D–L autoantibody which demonstrates bi-phasic hemolysin capability of causing serious hemolysis even when the titer detection is low, which is because of its capacity to detach itself from the lysed RBCs and consequently bind intact erythrocytes according to the temperature changes.
[6] Complement activation and consequent hemolysis would become reality if and only if binding-RBCs has travelled to the core part of the body at a warmer temperature around 37 °C (99 °F).
[3] Given the fact that hemoglobinuria as well as a personal history of exposure to cold temperatures are not always present, the diagnosis heavily relies on laboratory testing.
[16] It involves the cooling of the patient's serum to 4°C to allow the absorption of anti-P autoantibodies to the red cells, followed by warming to 37°C to activate complement fixation and hemolysis.
Neutrophil erythrophagocytosis is suggestive of PCH, while the absence of red cell agglutination as in CAD or microspherocytosis in WAIHA should also be noted.
The laboratory test results will reveal evaluations like anisocytosis, nucleated red blood cells, poikilocytosis, polychromasia, spherocytosis, and erythrophagocytosis by neutrophils.
[3] Anti-immunoglobulin G (anti-Ig) often disassociates itself from the surface of red blood cells under warm degrees of temperatures.
Each has a different underlying cause, management, and prognosis, making classification important when treating a patient with AIHA.
[29][30][31] 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.
[32] Long-term mild hemolytic anemia has been reported for several children who were in the likelihood of recurrence on exposure to any kind of cold or with illness.
[32] Case studies of those with recurrent DLHA suggest that repeated episodes of the hemolysis should not be regarded as false positive because the chances do truly exist when the patient has a D-L antibody to an antigen other than anti-P.[33][6] Chronic syphilis-associated DLHA resolves when the underlying disease receives appropriate treatment.