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Major forms include warm autoimmune hemolytic anemia, cold agglutinin disease, paroxysmal cold hemoglobinuria, and mixed AIHA. ",[68,74,78,82,86],{"key":69,"title":70,"html":71,"icon":72,"updatedAt":73},"","Overview","\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">AIHA is a group of immune-mediated hemolytic anemias in which antibodies target red blood cells and, in some cases, activate the complement system, causing shortened red blood cell survival.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">AIHA is classified according to the temperature at which the antibodies react most strongly and the underlying immune mechanism.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Warm autoimmune hemolytic anemia (wAIHA) is the most common form and is usually mediated by IgG antibodies that react near normal body temperature.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Cold agglutinin disease (CAD) is mainly mediated by cold-reactive IgM antibodies and complement activation. CAD has a distinct disease mechanism and treatment approach.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Paroxysmal cold hemoglobinuria (PCH) is another cold-reactive form of AIHA with a different mechanism and is more commonly seen in children following infections.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Mixed AIHA has features of both clinically significant warm and cold-reactive antibodies.\u003C\u002Fspan>\u003C\u002Fp>","⚕️","2026-10-09",{"key":69,"title":75,"html":76,"icon":77,"updatedAt":73},"Causes","\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">AIHA may be primary or secondary.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Primary AIHA means that no clear underlying condition is identified after evaluation. Secondary AIHA may be associated with:\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cul class=\" list-paddingleft-2\" style=\"list-style-type: disc;\">\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Autoimmune diseases such as systemic lupus erythematosus\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Lymphoid disorders such as lymphoma or chronic lymphocytic leukemia\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Certain infections\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Immunodeficiency\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Immune complications after hematopoietic stem cell transplantation\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Certain medications, including some antibiotics and other drugs\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003C\u002Ful>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">The associated conditions also vary by subtype.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">For example, CAD is often associated with a clonal B-cell disorder in the bone marrow, while secondary cold agglutinin syndromes may occur in association with infections or other diseases.\u003C\u002Fspan>\u003C\u002Fp>","🧬",{"key":69,"title":79,"html":80,"icon":81,"updatedAt":73},"Signs and Symptoms","\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Symptoms of AIHA result mainly from anemia and increased destruction of red blood cells and can range from mild to life-threatening.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Possible symptoms include:\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cul class=\" list-paddingleft-2\" style=\"list-style-type: disc;\">\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Fatigue and weakness\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Dizziness\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Rapid heartbeat or shortness of breath with activity\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Pale skin\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Yellowing of the skin or eyes\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Dark urine\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">An enlarged spleen\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Chest pain, breathing difficulty, or circulatory instability in severe anemia\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003C\u002Ful>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">wAIHA may develop gradually or present with rapid hemolysis. Some patients also develop immune thrombocytopenia, a combination known as Evans syndrome.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">In CAD, patients may also have cold-induced circulation symptoms such as bluish discoloration, pain, or numbness of the fingers, toes, ears, or nose. These symptoms often worsen with cold exposure.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">PCH may cause sudden intravascular hemolysis after cold exposure, sometimes accompanied by fever, chills, back pain, and hemoglobinuria.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Patients with active AIHA may also have an increased risk of thrombosis, particularly when hemolysis is severe.\u003C\u002Fspan>\u003C\u002Fp>","📋",{"key":69,"title":83,"html":84,"icon":85,"updatedAt":73},"Diagnosis","\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Diagnosis of AIHA requires evidence of both hemolysis and an immune cause.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Blood tests commonly include a complete blood count, reticulocyte count, bilirubin, lactate dehydrogenase (LDH), and haptoglobin.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Typical laboratory findings may include:\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cul class=\" list-paddingleft-2\" style=\"list-style-type: disc;\">\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Low hemoglobin\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Increased reticulocytes\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Increased indirect bilirubin\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Elevated LDH\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003Cli>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Reduced haptoglobin\u003C\u002Fspan>\u003C\u002Fp>\u003C\u002Fli>\u003C\u002Ful>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">However, not every patient meets the same fixed laboratory thresholds.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">The \u003Cstrong>direct antiglobulin test (DAT)\u003C\u002Fstrong> is a key diagnostic test. It detects IgG and\u002For complement components attached to red blood cells.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">DAT patterns can also help classify AIHA. wAIHA commonly shows IgG positivity, sometimes with complement, while CAD typically shows complement positivity.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Additional testing may include cold agglutinin titers for suspected CAD or Donath-Landsteiner antibody testing for suspected PCH.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">After AIHA is confirmed, further evaluation may be needed to look for an underlying autoimmune disease, infection, lymphoid disorder, medication trigger, or other cause.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Bone marrow testing is not required for every patient and is generally reserved for selected cases with unexplained cytopenias, suspected lymphoid disease, or diagnostic uncertainty.\u003C\u002Fspan>\u003C\u002Fp>","🩺",{"key":69,"title":87,"html":88,"icon":89,"updatedAt":73},"Treatment","\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Treatment depends strongly on the type of AIHA because wAIHA and CAD have different underlying mechanisms.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">When AIHA is secondary to another condition or medication, treatment of the underlying disorder or withdrawal of the suspected drug is also important.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cstrong>Warm AIHA\u003C\u002Fstrong>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cstrong>\u003Cbr\u002F>\u003C\u002Fstrong>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Corticosteroids remain the standard first-line treatment for wAIHA. Many patients respond initially, but relapse during or after steroid tapering is common, so reducing prolonged steroid exposure is an important treatment goal.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">For patients who do not respond adequately, become steroid-dependent, or relapse, \u003Cstrong>rituximab is now an important preferred second-line option\u003C\u002Fstrong>.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Other immunosuppressive therapies may be considered in selected patients. Splenectomy is still an option but is generally used later than in the past because other effective therapies are now available.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cstrong>Cold Agglutinin Disease\u003C\u002Fstrong>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cstrong>\u003Cbr\u002F>\u003C\u002Fstrong>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Treatment of CAD differs substantially from treatment of wAIHA.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Avoiding significant cold exposure remains helpful, but patients with symptomatic anemia, significant fatigue, or bothersome circulation symptoms may require drug therapy.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Corticosteroids are usually ineffective in CAD and are not routinely recommended.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Treatment may target the abnormal B-cell clone with therapies such as rituximab, or target complement-mediated hemolysis.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cstrong>Sutimlimab\u003C\u002Fstrong>, a monoclonal antibody targeting complement C1s, can rapidly reduce complement-mediated hemolysis and is approved for adults with CAD in several countries.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cstrong>Transfusion and Supportive Care\u003C\u002Fstrong>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cstrong>\u003Cbr\u002F>\u003C\u002Fstrong>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Red blood cell transfusion may be given when anemia is clinically significant.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">The decision to transfuse depends on symptoms, hemoglobin level and rate of decline, age, cardiovascular status, and overall clinical condition.\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">\u003Cbr\u002F>\u003C\u002Fspan>\u003C\u002Fp>\u003Cp style=\"margin: 7px 0;\">\u003Cspan style=\"font-size: 15px;\">Additional supportive care may include folate supplementation, prevention or treatment of thrombosis, and management of infections or other complications.\u003C\u002Fspan>\u003C\u002Fp>","💊",{"author":69,"reviewedBy":69,"lastReviewed":69,"datePublished":69,"citations":91,"disclaimer":69},[],false,1792294328401]