Elderly female, Group O Positive with a negative antibody screen received three single unit (OPOS) leuko-reduced red cell transfusions two weeks apart with no untoward effects. One week after last single unit transfusion, received two units (OPOS)on an outpatient basis and was discharged. One week later, received two units (OPOS) and experienced a febrile reaction with hemoglobinuria; she was admitted for a transfusion reaction workup. Post reaction sample was hemolyzed with a negative antibody screen and negative DAT. Full crossmatches performed with pre and post samples were compatible. Eluate was negative. Sample drawn immediately after(#1) reaction and one 24 hours post(#2) was referred to reference laboratory. Sample #1 acid eluate demonstrated Anti-D in saline; microscopic to weak positive with all cells in PEG, showing no specificity, unable to determine if anti-D is allo-or autoantibody. Serum hemolysis resolved in 24 hours. One week later admitted and transfused with two units ONEG leukoreduced red cells and again experienced a febrile hemolytic episode; DAT pre and post negative-hemolysis resolves in 24 hours. Two days later receives one unit (ONEG) washed red cells; no reaction or hemolysis. Next day, receives one unit (ONEG) washed red cells and experiences hemoglobinuria and post sample hemolyzed; again DAT negative. Finally, one week later, receives one unit (ONEG) washed red cells thru the blood warmer with no post hemoglobinuria or serum hemolysis.HELP!