Autoimmune Hemolytic Anemia Induced by Diclofenac

TO THE EDITOR: Diclofenac, a nonsteroidal antiinflammatory drug, rarely has been associated with hematologic ad~erse reactions. I v:e describe a case of severe diclofenac-induced autoimmune hemolytic anemia (AIHA) with acute renal failure. ., . A 64-year-old womanwasadmitted withseverehemo~ytlc anemia. ~I.ve days before admissionshe experiencedan episodeof backpam an~ a P~yslCIan prescribed diclofenac. Shedeniedtakinganyotherdrugs.Aftertakingdiclofenac the patientbeganto experience nausea. vomiting, abdominal pain,jaundice, anddark urine. The patient had a history of osteoarthritis. Two years before admission,an episode of AIHAoccurred afterseveral daysof ingesting diclofenac. She wasdischargedwith instructions to nevertake diclo~enac thereafter. O~er 1 ye~ of fo.llow-up.her hemoglobin concentration remained normaland direct antiglobulin tests(DA1') werenegative. On physical examination at the time of admission, she appeared pale and jaundiced butherabdomen wasnormal. Herhemoglobin was51 gIL.whiteblood cell count 32 x 109/L. and platelets261 x J09/L. Serumurea nitrogenwas 66.S mmollLof urea(IS7 mg/dL), creatinine 539 umol/l, (6.1 rng/dl.), totalbilirubin 75.S pmol/L (4.43 mg/dl.), lactate dehydrogenase 2000 U/L. and haptoglobin <O.IS gIL«IS mg/dL). DATwas strongly positive. coatedwithimmunoglobulin G and complement C3d.An indirect antiglobulin testand an antibody elution test werepositive. However. antibody specificity against redbloodcellantigens could notbe established. She was treatedwith prednisone60 mg/d,as well as large amountsof fluids and high-dose furosemide. However. her renal functiondeteriorated and the hemoglobin decreased to41 gIL(4.1 g/dL).Hemodialysis was initiated and continued for4 days.After5 unitsof packedredbloodcells were transfused. her renal function beganto improve. The patient'shemoglobin increased to SO gILand laboratoryindices of hemolysis stabilized within a weekof admission; DATbecame negative. One monthfollowing discharge, all laboratory indiceshad returned to normal and DAT was negative. Over6 monthsof follow-up, her hemoglobin and renal function havebeennormal andDAT hasremained negative. AIHA is an uncommon adverse reaction to diclofenac. Only I welldocumented case of AIHA after ingestion ofdiclofenac has been reported in the English literature. This patient's severe AIHA was associated with thrombocytopenia. Our patient had a history of diclofenac-associated AIHA 2 years before the reported abrupt episode, which suggested that prior immunization may have induced a more severe hemolysis with acute renal failure. In contrast to the previous report, our patient's platelet count was normal. There are 3 mechanisms of drug-induced AIHA: (I) drug adsorption on red blood cells, (2) immune-complex formation, and (3) induction of autoimmunity or drug-induced, warm antibody type AIHA.3 In our patient, as with the previous report, serologic test results were consistent with mechanism 3. This type of autoantibody reacts only with red blood cells and has no activity against the offending drug; alpha-methyldopa is the prototype. The serologic findings are indistinguishable from those arising in many cases of spontaneous AIHA. In conclusion, we emphasize the potentially severe nature of diclofenac-induced AIHA, and suggest that autoantibody induction is the mechanism of diclofenac-associated AIHA.