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Aplastic Anemia Following Acetazolamide Therapy
NOTES, CASES, INSTRUMENTS APLASTIC ANEMIA FOLLOWING ACETAZOLAMIDE T H E R A P Y MARVIN J. LÜBECK, M.D.
Denver, Colorado Acetazolamide (Diamox), a carbonic anhydrase inhibitor, is used widely in the treat ment of glaucoma. As a sulfonamide, it can produce hematopoietic suppression. Five such cases have been previously reported. To these cases is added one of aplastic anemia resulting in death following the use of aceta zolamide. C A S E REPORT
A 66-year-old man was seen on February 4, 1969, with a history of right eye pain and redness for one week. There was no history of allergy. Ocular examination revealed corrected vision, right: light projection, and left: 20/40. Intraocular pressure by applanation was, right: SO mm Hg., and left: 30 mm Hg. Gonioscopy showed a closed angle in the right eye and a very narrow angle in the left. Tangent screen visual field of the left eye was normal with a 2-mm test object at 1-m testing distance. The patient was treated with 4% pilocarpine eyedrops, 500 mg of acetazolamide immediately, followed by 250 mg four times a day, and oral glycerine. On February 26, peripheral iridectomy was performed on the right eye. Postoperatively, he received topical atropine and neomycin-polymyxindexamethasone (Maxitrol) to the right eye, and pilocarpine to the left. During this hospitalization, the WBC count was 7400 mm3, and the hemoglobin was 13.9 g/100 ce.
days with lincomycin without response. Penicillin had been started the day prior to admission. The patient denied using any other medications, except for the pilocarpine eyedrops and acetazolamide. He had been retired for two years and had had no ex posure to toxic materials. He stated that he had had progressive weight loss over the previous one to two years. Physical examination revealed dry lips with cracks and bleeding at the corners. The tongue was dry and partly covered by yellow-brown material. A purulent tonsillitis was present. There was no bleeding from the gums. There were areas of ecchymosis of the skin of the arms and legs. Admission temperature was 102°F (rectally). WBC count was 1000 with 22 segs, 4 stabs, 70 lympho cytes, and 4 monocytes. Platelets were decreased. Hemoglobin was 12.5 g/100 ml. Prednisone and methyltestosterone were started. Parenteral fluids and a unit of blood were given. On June 19, fol lowing hydration, WBC was 700, hemoglobin was 9.7, and platelet count was 6500/mm3. Bone mar row was reported as markedly hypoplastic with no evidence of megakaryocytes. Reticulocyte count was 0.1%. There were occasional aggregates of cells of the granulocytic series with a shift to the immature side and a maturation arrest. A few red cell pre cursors were noted with maturation arrest. Lym phocytes and plasma cells were not remarkable. The bone marrow and peripheral blood findings were felt to be consistent with a diagnosis of aplastic anemia. The patient continued to receive prednisone, methyltestosterone, and whole blood, but died on June 21, 1969. Permission for necropsy was denied. COMMENT
This patient had no known exposure to toxic substances, and had been taking no On March 8, 1969, acetazolamide, 125 mg four systemic medications other than acetazola times a day, was instituted. On March 22, this was mide. There would therefore appear to be a increased to 250 mg four times a day. On May 10, relationship between the acetazolamide and this was changed to a 500 mg (Sequel) twice a day, and the topical neomycin-polymyxin-dexamethasone his aplastic anemia. Acetazolamide has been a was discontinued. most valuable drug in the treatment of glau On June 7, 1969, the patient complained of some coma. It has been reported to induce myopia, loss of appetite and headache. On June 17, he was admitted to the hospital. His family doctor had renal colic, and gouty arthritis, none a threat been treating him for acute tonsillitis for three to life. Kristinsson 1 wrote of a man who died of cholestatic jaundice considered com From the Section of Ophthalmology, Department patible with drug intoxication after receiving of Surgery, University of Colorado School of Medicine. Presented before the Colorado Ophthal- 13 g of acetazolamide in 26 days. There have mological Society November 15, 1969. been five previously reported cases of hema Reprint requests to Marvin J. Lübeck, M.D., 3865 Cherry Creek North Drive, Denver, Colorado topoietic suppression. Pearson, Binder, and Neber2 reported a case in a patient who had 80209. 684
VOL. 69, NO. 4
NOTES, CASES, INSTRUMENTS
received the drug in a dose of 250 mg daily irregularly for three months, and who recov ered after discontinuation of the drug and treatment with penicillin, streptomycin, and ACTH. The patient described by Under wood3 died. He had received 250 mg of acetazolamide daily for one month. In Hoff man's 4 case, the patient had 250 mg of acetazolamide five days weekly for about seven weeks, developed agranulocytosis, and died. Two patients have been reported to develop thrombocytopenia, one by Reisner and Morgan 5 after three weeks of acetazolamide and one by Bertino, Rodman, and Myerson" after only nine days of acetazolamide. Most of these cases received small doses of acetazolamide for a short duration com pared to the dosage and duration employed in many glaucoma patients. It would thus seem that this is a toxic effect of acetazola mide that is not dose-related. It is currently believed that sulfonamide-induced hematopoietic suppression is the result of an abnor mal immunologie reaction. This raises the question as to the desirability of blood stud ies in patients being started on acetazola mide therapy, particularly during the early weeks of its use.
685
J. D. : Fatal agranulocytosis associated with aceta zolamide. New Eng. J. Med. 262:242, 1960. 5. Reisner, E. H., and Morgan, M.D. : Thrombo cytopenia following acetazolamide therapy. J.A.M.A. 160:206, 1956. 6. Bertino, J. R., Rodman, T., and Myerson, R. M. : Thrombocytopenia and renal lesions associated with acetazolamide therapy. Arch. Int. Med. 99:1006, 1957.
SPONGE H O L D E R FOR CRYOEXTRACTION M. HARVEY RUBIN,
M.D.
Chapel Hill, North Carolina
REFERENCES
Techniques of cryoextraction in cataract surgery have made lens removal in many cases less complicated. However, serious problems still exist, such as the inadvertent inclusion of the iris in the ice ball as it forms between the instrument and lens. At tempts have been made to prevent this acci dent by the use of iris retractors. Many iris retractors, both plastic and metal, are avail able. These vary in shape and size, from a double-end Teflon retractor to a disk-shaped steel instrument. Any of these, however, may tear, disinsert or avulse the iris, as well as make possible the rupture of the lens cap sule or vitreous face. A safer approach to this problem, which eliminates the conventional iris retractors, is the use of a cellulose sponge. This method initially introduced by Kristensen 1 of Den mark and later by Small,2 as well as Jepson and Wetzig, 3 utilizes a triangular piece of cellulose sponge supported by a hemostat or a forceps. An instrument to hold a sponge for this purpose consists of a locking-type forceps*
1. Kristinsson, A.: Fatal reaction to acetazola mide. Brit. J. Ophth. 51:348,1967. 2. Pearson, J. R., Binder, C. I., and Neber, J. : Agranulocytosis following Diamox therapy. J.A.M.A. 157:339, 19SS. 3. Underwood, L. C. : Fatal bone marrow depres sion after treatment with acetazolamide. J.A.M.A. 161:1477, 19S6. 4. Hoffman, F. G., Zimmerman, S. L., and Reese,
From the Division of Ophthalmology, University of North Carolina School of Medicine, Chapel Hill, North Carolina. Reprint requests to M. Harvey Rubin, M.D., 1311 North Elm Street, Greensboro, North Carolina 27401. * Locking-type forceps and cellulose sponges are manufactured by Edward Week and Company, Inc., New York, New York.
SUMMARY
A case report is presented of a fatal aplastic anemia following the use of acetazo lamide in the treatment of glaucoma. This patient received approximately 116 g of acetazolamide over a period of four and onehalf months. Hematopoietic suppression has been known to occur with sulfonamide com pounds. This is thought to be an abnormal immunologie reaction that is not dose-related.
Denver, Colorado Acetazolamide (Diamox), a carbonic anhydrase inhibitor, is used widely in the treat ment of glaucoma. As a sulfonamide, it can produce hematopoietic suppression. Five such cases have been previously reported. To these cases is added one of aplastic anemia resulting in death following the use of aceta zolamide. C A S E REPORT
A 66-year-old man was seen on February 4, 1969, with a history of right eye pain and redness for one week. There was no history of allergy. Ocular examination revealed corrected vision, right: light projection, and left: 20/40. Intraocular pressure by applanation was, right: SO mm Hg., and left: 30 mm Hg. Gonioscopy showed a closed angle in the right eye and a very narrow angle in the left. Tangent screen visual field of the left eye was normal with a 2-mm test object at 1-m testing distance. The patient was treated with 4% pilocarpine eyedrops, 500 mg of acetazolamide immediately, followed by 250 mg four times a day, and oral glycerine. On February 26, peripheral iridectomy was performed on the right eye. Postoperatively, he received topical atropine and neomycin-polymyxindexamethasone (Maxitrol) to the right eye, and pilocarpine to the left. During this hospitalization, the WBC count was 7400 mm3, and the hemoglobin was 13.9 g/100 ce.
days with lincomycin without response. Penicillin had been started the day prior to admission. The patient denied using any other medications, except for the pilocarpine eyedrops and acetazolamide. He had been retired for two years and had had no ex posure to toxic materials. He stated that he had had progressive weight loss over the previous one to two years. Physical examination revealed dry lips with cracks and bleeding at the corners. The tongue was dry and partly covered by yellow-brown material. A purulent tonsillitis was present. There was no bleeding from the gums. There were areas of ecchymosis of the skin of the arms and legs. Admission temperature was 102°F (rectally). WBC count was 1000 with 22 segs, 4 stabs, 70 lympho cytes, and 4 monocytes. Platelets were decreased. Hemoglobin was 12.5 g/100 ml. Prednisone and methyltestosterone were started. Parenteral fluids and a unit of blood were given. On June 19, fol lowing hydration, WBC was 700, hemoglobin was 9.7, and platelet count was 6500/mm3. Bone mar row was reported as markedly hypoplastic with no evidence of megakaryocytes. Reticulocyte count was 0.1%. There were occasional aggregates of cells of the granulocytic series with a shift to the immature side and a maturation arrest. A few red cell pre cursors were noted with maturation arrest. Lym phocytes and plasma cells were not remarkable. The bone marrow and peripheral blood findings were felt to be consistent with a diagnosis of aplastic anemia. The patient continued to receive prednisone, methyltestosterone, and whole blood, but died on June 21, 1969. Permission for necropsy was denied. COMMENT
This patient had no known exposure to toxic substances, and had been taking no On March 8, 1969, acetazolamide, 125 mg four systemic medications other than acetazola times a day, was instituted. On March 22, this was mide. There would therefore appear to be a increased to 250 mg four times a day. On May 10, relationship between the acetazolamide and this was changed to a 500 mg (Sequel) twice a day, and the topical neomycin-polymyxin-dexamethasone his aplastic anemia. Acetazolamide has been a was discontinued. most valuable drug in the treatment of glau On June 7, 1969, the patient complained of some coma. It has been reported to induce myopia, loss of appetite and headache. On June 17, he was admitted to the hospital. His family doctor had renal colic, and gouty arthritis, none a threat been treating him for acute tonsillitis for three to life. Kristinsson 1 wrote of a man who died of cholestatic jaundice considered com From the Section of Ophthalmology, Department patible with drug intoxication after receiving of Surgery, University of Colorado School of Medicine. Presented before the Colorado Ophthal- 13 g of acetazolamide in 26 days. There have mological Society November 15, 1969. been five previously reported cases of hema Reprint requests to Marvin J. Lübeck, M.D., 3865 Cherry Creek North Drive, Denver, Colorado topoietic suppression. Pearson, Binder, and Neber2 reported a case in a patient who had 80209. 684
VOL. 69, NO. 4
NOTES, CASES, INSTRUMENTS
received the drug in a dose of 250 mg daily irregularly for three months, and who recov ered after discontinuation of the drug and treatment with penicillin, streptomycin, and ACTH. The patient described by Under wood3 died. He had received 250 mg of acetazolamide daily for one month. In Hoff man's 4 case, the patient had 250 mg of acetazolamide five days weekly for about seven weeks, developed agranulocytosis, and died. Two patients have been reported to develop thrombocytopenia, one by Reisner and Morgan 5 after three weeks of acetazolamide and one by Bertino, Rodman, and Myerson" after only nine days of acetazolamide. Most of these cases received small doses of acetazolamide for a short duration com pared to the dosage and duration employed in many glaucoma patients. It would thus seem that this is a toxic effect of acetazola mide that is not dose-related. It is currently believed that sulfonamide-induced hematopoietic suppression is the result of an abnor mal immunologie reaction. This raises the question as to the desirability of blood stud ies in patients being started on acetazola mide therapy, particularly during the early weeks of its use.
685
J. D. : Fatal agranulocytosis associated with aceta zolamide. New Eng. J. Med. 262:242, 1960. 5. Reisner, E. H., and Morgan, M.D. : Thrombo cytopenia following acetazolamide therapy. J.A.M.A. 160:206, 1956. 6. Bertino, J. R., Rodman, T., and Myerson, R. M. : Thrombocytopenia and renal lesions associated with acetazolamide therapy. Arch. Int. Med. 99:1006, 1957.
SPONGE H O L D E R FOR CRYOEXTRACTION M. HARVEY RUBIN,
M.D.
Chapel Hill, North Carolina
REFERENCES
Techniques of cryoextraction in cataract surgery have made lens removal in many cases less complicated. However, serious problems still exist, such as the inadvertent inclusion of the iris in the ice ball as it forms between the instrument and lens. At tempts have been made to prevent this acci dent by the use of iris retractors. Many iris retractors, both plastic and metal, are avail able. These vary in shape and size, from a double-end Teflon retractor to a disk-shaped steel instrument. Any of these, however, may tear, disinsert or avulse the iris, as well as make possible the rupture of the lens cap sule or vitreous face. A safer approach to this problem, which eliminates the conventional iris retractors, is the use of a cellulose sponge. This method initially introduced by Kristensen 1 of Den mark and later by Small,2 as well as Jepson and Wetzig, 3 utilizes a triangular piece of cellulose sponge supported by a hemostat or a forceps. An instrument to hold a sponge for this purpose consists of a locking-type forceps*
1. Kristinsson, A.: Fatal reaction to acetazola mide. Brit. J. Ophth. 51:348,1967. 2. Pearson, J. R., Binder, C. I., and Neber, J. : Agranulocytosis following Diamox therapy. J.A.M.A. 157:339, 19SS. 3. Underwood, L. C. : Fatal bone marrow depres sion after treatment with acetazolamide. J.A.M.A. 161:1477, 19S6. 4. Hoffman, F. G., Zimmerman, S. L., and Reese,
From the Division of Ophthalmology, University of North Carolina School of Medicine, Chapel Hill, North Carolina. Reprint requests to M. Harvey Rubin, M.D., 1311 North Elm Street, Greensboro, North Carolina 27401. * Locking-type forceps and cellulose sponges are manufactured by Edward Week and Company, Inc., New York, New York.
SUMMARY
A case report is presented of a fatal aplastic anemia following the use of acetazo lamide in the treatment of glaucoma. This patient received approximately 116 g of acetazolamide over a period of four and onehalf months. Hematopoietic suppression has been known to occur with sulfonamide com pounds. This is thought to be an abnormal immunologie reaction that is not dose-related.