Refractory Immune Hemolytic Anemia With A High Thermal Amplitude, Low Affinity IgG Anti-Pr _a Cold Autoantibody

Abstract

A 54 y.o. woman presented with acute Coombs-negative hemolytic anemia at an outside hospital where she received 25 RBC transfusions and did not respond to prednisone or splenectomy. On transfer to our hospital, routine DAT and IAT were weakly positive, occasionally negative. When a modified "cold" antiglobulin test was employed, the result was strongly positive for IgG, weakly positive for C3d. Cold agglutinin titer was 32, and the Donath-Landsteiner test was negative. The autoantibody exhibited Pra specificity. The patient failed IV-IgG, high dose IV pulse steroids and cyclophosphamide, and continued to require daily transfusions. She responded 21 days after receiving daily plasma exchange (x3), with pulse cyclophosphamide on the third day, followed by escalating daily oral cyclophosphamide.

Life‐threatening hemolytic anemia due to an autoanti‐Pr cold agglutinin: evidence that glycophorin A antibodies may induce lipid bilayer exposure and cation permeability independent of agglutination

“…The hemolysis was not associated with activation of complement by either the classic or the alternative pathways despite the patient's serum containing complement responsive to activation by both pathways. The immunoglobulin isotypes of the anti-Pr CAs in patients with severe or fatal hemolysis have varied: monoclonal 2,19,20 and polyclonal IgG, 21 an IgA (D. Roelcke, personal communication, 1999), and five due to IgM. 3,5,8,[22][23][24] Evidence for complement activation was reported in some patients, 22,23 variable in some patients, 19,21 and not reported in others.…”

“…The immunoglobulin isotypes of the anti-Pr CAs in patients with severe or fatal hemolysis have varied: monoclonal 2,19,20 and polyclonal IgG, 21 an IgA (D. Roelcke, personal communication, 1999), and five due to IgM. 3,5,8,[22][23][24] Evidence for complement activation was reported in some patients, 22,23 variable in some patients, 19,21 and not reported in others. 2,20,24 The use of the fluorescent probe Fluo-3 to estimate intracellular Ca 2+ and the large gradient of Ca 2+ across the membrane of RBCs permits rapid 25 These authors, furthermore, showed that binding of this PE to cinnamycin interfered with cell division.…”

Synchronization of plasma exchange and cyclophosphamide in severe and refractory autoimmune hemolytic anemia

“…The auto-antibody was a polyclonal IgG, of high thermal amplitude, low affinity, and with Pra specificity, titer 1:4,000. A detailed description of the serologic investigations was reported by Ramos et al [14]. During her first 74 days of hospitalization she required an average of one red cell transfusion (PRC) daily.…”

Autoimmune hemolytic anemia caused by IgG λ‐monotypic cold agglutinins of anti‐Pr specificity after rubella infection

“…IgG CAs are rare. Ten cases were reviewed in 1990, 14 and an additional case was reported in 1992 15 . At least 5 of the 11 patients had severe hemolysis (Hb <7 g/dL), and 3 had a negative DAT.…”