Diagnosis is made by first ruling out other causes of hemolytic anemia, such as G6PD, thalassemia, sickle-cell disease. Clinical history is also important to elucidate any underlying illness or medications that may have led to the disease. Laboratory investigations are carried out to determine the etiology of the disease. Following confirmation of hemolysis (seen with laboratory markers of low hemoglobin, elevated LDH, decreased haptoglobin, and elevated unconjugated bilirubin), a direct antiglobulin test (DAT)(also known as a Coomb's test) is done to show auto-immune pathogenesis with antibodies, compliment or both on the erythrocyte surface. This is followed by a monospecific DAT that identifies the specific antibody and compliment types on the erythrocyte surface. In cold agglutinin disease, the monospecific DAT is by definition positive for the compliment molecule C3d but IgM may be negative as the molecule may detach at the time of testing. The diagnosis of cold agglutinin disease is confirmed with an elevated cold agglutinin titer. A bone marrow biopsy is used in<unk>  to identify a possible underlying lymphoproliferative disorder. Classification<unk>  can be classified as warm<unk>  or cold<unk> , which includes cold agglutinin disease and paroxysmal cold hemoglobinuria. These classifications are based on the characteristics of the autoantibodies involved in the pathogenesis of the disease. Each has a different underlying cause, management, and prognosis, making classification important when treating a patient with<unk> . ----<unk>  ::*Warm-antibody type :::*Primary :::*Secondary (lymphoproliferative disorders, autoimmune disorders) ::*Cold-antibody type (anemia) :::*Primary cold agglutinin disease :::*Secondary cold agglutinin syndrome ::::*Associated with malignant disease ::::*Acute, transient, infection-associated (acute cold antibody mediated<unk>  complicating Mycoplasma pneumoniae or viral infections) ::::*Chronic (lymphoproliferative disorders) ::*Paroxysmal cold hemoglobinuria :::*Idiopathic :::*Secondary ::::*Acute, transient (Infections other than syphilis) ::::*Chronic (syphilis) ::*Mixed cold- and warm-antibody type :::*Idiopathic :::*Secondary (lymphoproliferative disorders, autoimmune disorders) ::*Drug-induced immune hemolytic anemia :::*Autoimmune type :::*Drug absorption type :::*Neoantigen type Evidence for hemolysis The following findings may be present: * Increased red cell breakdown * Elevated serum bilirubin (unconjugated) * Excess urinary urobilinogen * Reduced plasma haptoglobin * Raised serum lactic dehydrogenase (LDH) * Hemosiderinuria * Methemalbuminemia * Spherocytosis * Increased red cell production: * Reticulocytosis * Erythroid hyperplasia of the bone marrow ;Specific investigations * Positive direct Coombs test
Autoimmune hemolytic anemia
Mixed autoimmune hemolytic anemia
Cold autoimmune hemolytic anemia
Acquired hemolytic anemia
Microangiopathic hemolytic anemia
Mechanical hemolytic anemia
Drug-induced nonautoimmune hemolytic anemia
Cryoglobulinemia