Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person’s own red blood cells (RBCs) cause them to burst (lyse), leading to. Autoimmune hemolytic anemia (AIHA) is an uncommon disorder characterized by hemolysis mediated by autoantibodies directed against. Autoimmune hemolytic anemia is characterized by shortened red blood cell survival and a positive Coombs test. The responsible autoantibodies may be either.
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Autoimmune hemolytic anemia is characterized by shortened red blood cell survival and a positive Coombs test. The responsible autoantibodies may be either warm reactive or cold reactive. The rate of hemolysis and the severity of the anemia may vary from mild to severe and life-threatening. Diagnosis is made in the laboratory by the findings of anemia, reticulocytosis, a positive Coombs test, and specific serologic tests.
The prognosis is generally good but renal failure and death sometimes occur, especially in cases mediated by drugs. Autoimmune hemolytic anemia AIHA exhibits two important characteristics: In cryopathic hemolytic syndromes, cold-reactive autoantibodies exhibit affinity for RBCs optimally at temperatures below body temperature.
In adults, most of the cold-reactive antibodies are agglutinins of the IgM isotype. In children, cold hemolysins generally IgG are most common. Unusual patients with mixed AIHA exhibit both cold-reactive and warm-reactive autoantibodies [ 56 ]. Each of these types of AIHA may be sub-classified based on the presence or absence of underlying diseases.
In the absence of an underlying disease, the AIHA is termed primary or idiopathic. Rather, AIHA should be considered secondary only when i AIHA and the suspect disease occur together more frequently than by chance alone, ii AIHA remits with correction of the suspect disease, or iii the suspect disease causes immunologic aberration [ 3 ].
Certain drugs also mediate immune injury to RBCs. Three mechanisms are recognized and two of these involve elements of autoimmunity, in which autoantibodies recognize and bind to specific RBC epitopes in concert with drugs or their metabolites or in which the autoantibody binds to RBC epitopes without the presence of drug [ 7 ]. Classification of AIHA modified from [ 1 ]. Annual incidence of warm antibody AIHA is estimated at one per 75, population, occurring in people of all ages [ 3 ]. Primary warm antibody AIHA accounts for about half of the cases [ 34 ].
The presenting symptoms of warm antibody AIHA are commonly related to the anemia itself. Typically, onset of symptoms is insidious over months. Less often a patient may note sudden onset of symptoms of severe anemia and jaundice over a few days.
In secondary AIHA, the symptoms and signs of the underlying disease may overshadow the hemolytic anemia and associated features.
In idiopathic warm antibody AIHA with only mild anemia, the physical examination is usually unremarkable. Even patients with severe hemolysis may have only mild splenomegaly. In very severe cases, including those with acute onset, patients may present with fever, pallor, jaundice, fig.
Physical examination in warm antibody AIHA. Skin pallor, icterus and nailbed pallor in a patient with treatment-refractory warm AIHA, hemoglobin 4.
The Clinical Pictures of Autoimmune Hemolytic Anemia
Salama, with kind permission adalzh the patient. The prevalence is estimated at about 14 per million [ 8 ]. It is more common in women than in men [ 23 ]. Idiopathic primary chronic cold agglutinin disease has its peak incidence after age 50 years. This disorder is characterized by monoclonal IgM cold agglutinins and is considered a special form of monoclonal gammopathy or low-grade lymphoproliferative malignancy.
The majority of these patients exhibit clonal B-lymphocyte proliferation [ 8 ]. Other patients with established lymphoproliferative disorders may develop cold agglutinin disease as a manifestation of the lymphoma.
Diagnosis and treatment of autoimmune hemolytic anemia: classic approach and recent advances
Cases associated with symptomatic lymphoproliferative disorders are said to represent secondary cold agglutinin disease. Most patients with idiopathic cold agglutinin disease have chronic hemolytic anemia.
These patients usually possess cold agglutinins of high thermal amplitude, i. Other hemolirik exhibit episodic, acute hemolysis with hemoglobinuria induced by chilling.
In these patients, one tends to see antibodies with lower thermal amplitude requiring more severe chilling for the agglutinin to bind to RBCs.
Secondary cold he,olitik disease is seen in adolescents or young adults with Mycoplasma pneumoniae infections, infectious mononucleosis and, sometimes in children with chickenpox. It is a self-limited process. Most patients with mycoplasma pneumonia have high cold asalah titers, but clinical hemolytic anemia is unusual [ 9 ]. The hemolysis is self-limited, lasting weeks [ 3 ]. Hemolytic anemia in infectious mononucleosis develops within the first 3 weeks of illness [ 10 ]. Jaundice may be present.
Livedo reticularis is occasionally seen fig.
Acrocyanosis involving the fingers, toes, nose, and ears is caused by sludging of RBCs in the cutaneous microvasculature fig. Skin ulceration and necrosis are uncommon. Other physical findings are variable and depend upon the presence and nature of an underlying disease. Splenomegaly, a characteristic finding in lymphoproliferative diseases or infectious mononucleosis, may be observed in idiopathic cold agglutinin disease.
Physical examination in cold antibody AIHA. Cold agglutinin related acrocyanosis and paroxysmal hemolysis. Eur J Vasc Endovasc Surg, However, among children, Donath-Landsteiner hemolytic anemia accounts for almost one-third of cases [ 11 ].
Most childhood cases follow either specific viral infections or upper respiratory infections of undefined etiology [ 231112 ]. In paroxysmal cold hemoglobinuria, constitutional symptoms are prominent during a paroxysm. A few minutes to hours after cold exposure, the patient develops aching pains in the back or legs, abdominal cramps, and headaches. Chills and fever typically follow. Hemoglobinuria is observed shortly after onset of symptoms. The constitutional symptoms and hemoglobinuria generally last a few hours.
Raynaud phenomenon and cold urticaria sometimes occur during an attack; jaundice may follow. The incidence of drug-induced immune hemolytic anemia is about one per million. The great majority result from the second- and third-generation cephalosporins, cefotetan, and ceftriaxone [ 13 ].
A careful history of drug exposure should be elicited from all patients with hemolytic anemia or a positive DAT. The clinical picture is quite variable. As with other hemolytic anemias, the severity of symptoms depends upon the rate of hemolysis, which may be slow and mild or rapid and severe.
Acute renal failure and death may accompany severe hemolysis [ 141516 ]. Occasional patients have leukopenia and neutropenia [ 17 ]. Platelet counts are usually normal. Occasionally immune thrombocytopenia is seen in patients with warm antibody AIHA, a condition termed Evans syndrome [ 17 ]. Patients with paroxysmal cold hemoglobinuria exhibit a rapid fall in hematocrit during a paroxysm. During a paroxysm, leukopenia is noted early, followed by leukocytosis.
Consumption of complement proteins during hemolysis may lead to depression of complement levels. In drug-induced immune hemolytic anemia, the hematologic findings are similar to those of warm antibody AIHA at one end of a spectrum, or may be as severe as those seen in paroxysmal cold hemoglobinuria at the other end, depending on the mechanism of the drug-induced immune process.
Most patients exhibit anemia and reticulocytosis. The blood film exhibits several features common to all types of AIHA. Polychromasia represents reticulocytosis, reflecting an increased production and egress of reticulocytes from the marrow. Spherocytes are frequently seen, a finding that suggests the presence of either hereditary spherocytosis HS or an immune hemolytic process. Mild leukocytosis and neutrophilia are typical.
RBC autoagglutination may be seen in the blood film and in chilled anticoagulated blood from patients with cold-antibody AIHA fig. Blood films from patients with AIHA. Used with permission from Lichtman’s Atlas of Hematology, www. Note agglutination of RBCs.
The reticulocyte count usually is elevated.
The Clinical Pictures of Autoimmune Hemolytic Anemia
Nevertheless, early on, more than one-third of patients may exhibit transient reticulocytopenia [ 1819 ]. Reticulocytopenia also may be seen in patients with compromised marrow function, parvovirus infection, toxic chemicals, or nutritional deficiency.
Marrow examination is not necessary for the diagnosis, but usually reveals erythroid hyperplasia. Sometimes there is evidence of an underlying lymphoproliferative disorder. Increased unconjugated bilirubin is characteristic of hemolytic anemia.
Urinary urobilinogen is increased but bilirubin is not detected in the urine unless serum conjugated bilirubin is increased. Serum haptoglobin levels are low, and lactate dehydrogenase levels are increased. Hemoglobinuria is rare in warm antibody AIHA but is more common in patients with cold agglutinin disease, and especially hemilitik patients with paroxysmal cold hemoglobinuria adalxh with some types of drug-induced immune hemolytic anemia. A broad-spectrum antiglobulin reagent detects both immunoglobulin and complement components on patient RBCs.
More specific reagents which react selectively with IgG or with C3 are used to determine which sensitizing agents are present adxlah the RBCs. Monospecific antisera to IgM or IgA may be used in selected cases [ 1 ].
IgG alone, complement alone, and IgG plus complement. Each pattern is associated with active hemolysis. There are 3 principle causes for the negative DAT: IgG or complement sensitization below the threshold of detection of antiglobulin reagents; low-affinity IgG causing loss of cell-bound antibody during the cell washing steps before the direct antiglobulin reaction; sensitization with IgA or IgM antibodies which many commercial DAT reagents cannot detect because they contain only anti-IgG and anti-C3.