Warm Reactive Autoantibodies: Clinical and Serologic Correlations

Abstract

Warm reactive autoantibodies are encountered relatively frequently in tertiary care hospitals. We studied 100 consecutive patients with warm autoantibodies to correlate their clinical and serologic features. Study patients (56 male, 44 female) had various diagnoses and a mean age of 53.5 years (range, 3-90 years). Autoimmune hemolysis was documented in 29 patients; 20 patients (69%) in this subset had diseases classically associated with warm autoimmune hemolytic anemia (hematologic and autoimmune disorders). All study patients demonstrated IgG on their RBCs (direct antiglobulin test [DAT] reactivity range, microscopic to 4+); 49 also demonstrated C3 (reactivity range, microscopic to 3+). The DAT for IgG was 2+ or more in 25 (86%) of 29 patients with hemolysis; the DAT for IgG was 1+ or less in 45 (63%) of 71 patients without hemolysis. In patients with hemolysis, 21 (72%) of 29 had a DAT reactive for C3. These findings may be useful in determining the clinical significance of warm autoantibodies and the extent to which patients should be followed up for hemolysis.

Warm Red Blood Cell Autoantibodies and the Direct Antiglobulin Test Revisited

“…Thus, while a DAT result of 2+ or greater in strength often is associated with hemolysis, the association is not 100% and significant numbers of patients do not demonstrate increased RBC destruction despite what appears to be significant antibody coating of RBCs. The majority of patients in the study by Wheeler et al 14 did not demonstrate hemolysis.…”

“…Although Wheeler et al 14 have not definitively answered the recurring question of the relationship to RBC-bound antibody and destruction, their study reminds us that patients with autoimmune hemolysis tend to be complicated cases-clinically and in the laboratory-and, in any individual patient, diagnosis and treatment will depend on close interaction with the transfusion medicine physician and the patient's physician. As noted by another observer, "Meaningful prediction of clinical severity requires the physician to synthesize assessments of the maximum possible number of the diverse factors that combine to cause autoimmune hemolysis in vivo."…”

Autoimmune Hemolytic Anemia and Red Blood Cell Autoantibodies

“…In a study categorizing 100 patients with warm autoantibodies, the most frequently associated clinical conditions were hematologic malignancies and autoimmune disorders followed by cardiac disease and nonhematologic malignancies. 2 …”

“…The strength of DAT agglutination can help because increased agglutination and the presence of complement has been suggested to correlate with the hemolysis. 2 The presence of both hemolysis and RBC autoantibodies does not always mean AIHA, and other causes of hemolysis, such as medications, microangiopathic hemolysis, or parasitemia, need to be considered. Because of the association of RBC autoantibodies with an underlying disorder, a new-onset RBC autoantibody may prompt a clinician to investigate, for example, for the presence of a lymphoproliferative disorder.…”

“…For example, 7.6% of all antibody workups at our institution involve RBC autoantibodies, which is similar to the 7% incidence reported elsewhere. 2 Although RBC autoantibodies are seen in patients of all ages, a general increase in incidence is observed with age, most dramatically in patients older than 50 years. 3 The RBC autoantibodies are generally classified as either warm RBC autoantibodies, if optimum reactivity with RBCs occurs at 378C, or cold RBC autoantibodies, if optimum reactivity with RBCs occurs at less than 308C.…”