Cefuroxime-Induced Thrombocytopenia?
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Spontaneous cure of osteitis fibrosa cystica 757 1 Norris EH. Primary hyperparathyroidism. Arch Pathol 1946; 6 Norton JA, Aurbach GD, Marx SJ, Doppman JL. Surgical 42: 261-73. management of hyperparathyroidism. In: De Groot LJ, ed. 2 Minisola S, Romagnoli E, Scarnecchia L, et al. Parathyroid Endocrinology. Philadelphia: WB Saunders, 1989; pp 1013- Postgrad Med J: first published as 10.1136/pgmj.72.854.757 on 1 December 1996. Downloaded from storm: immediate recognition and pathophysiological con- 31. siderations. Bone 1993; 14: 703-6. 7 Brown EM, Wilson RE, Thatcher JG, Marynick SP. 3 Howard JE, Follis RH, Yendt ER, Connor TB. Hyperpar- Abnormal calcium regulated PTH release in normal athyroidism. Case report illustrating spontaneous remission parathyroid tissue from patients with adenoma. Am Jf Med due to necrosis of adenoma. J Clin Endocninol Metab 1953; 1981; 71: 565-74. 13: 997-1008. 8 Peck WW, Higgins CB, Fisher MR, et al. Hyperparathyr- 4 Frost HM. Bone remodeUling and its relationship to metabolic oidism: comparison of MR imaging with radionuclide bone disease. Springfield IL: Charles C Thomas, 1973. scanning. Radiology 1987; 163: 415-20. 5 Aurbach GD, Marx SJ, Spiegal AM. Parathyroid hormone, 9 Lumb GA, Stanbury SW. Parathyroid function in human calcitonin and calciferols. In: Wilson JD, Foster DW, eds, vitamin D deficiency and vitamin D deficiency in primary Williams textbook of endocrinology. Philadelphia: WB Saun- hyperparathyroidism. Am J Med 1974; 56: 8335. ders, 1985. Cefuroxime-induced thrombocytopenia? Peter Aitken, SMN Zaidi Summary admission. Investigations included full blood We present the case of a 77-year-old man count, erythrocyte sedimentation rate, mid- who became thrombocytopenic whilst stream urine and urinary electrolytes, liver treated parenterally with cefuroxime in function tests, calcium, glucose, thyroid func- the absence of proven infection and re- tion tests, VDRTIPA, three sets of blood covered when the cefuroxime was discon- cultures, malarial parasites, a chest X-ray and tinued. an electrocardiogram. The significant preliminary result was Keywords: cefuroxime, thrombocytopenia growth ofa Staphylococcus species (unspecified) in one blood culture bottle. We commenced cefuroxime 750 mg tid parenterally. We re- Since 1966 there have been a number of case peated the full blood count on days one and reports suggesting a link between cephalospor- three of cefuroxime therapy and noted the in therapy and blood dyscrasias, especially platelet count to have fallen to 92 x 109/1. We http://pmj.bmj.com/ thrombocytopenia.1 In each case the causal considered this to be due to presumed infec- link remains unproven because of the presence tion or a side-effect of medication. On day five of confounding variables and the ethical posi- of cefuroxime therapy we received the final tion that precludes re-exposure of the sensitive microbiological report on the blood culture individual to confirm the cause and effect. An identifying the organism as Staphylococcus immunological mechanism has been described epidermidis, a contaminant skin commensal. in cefotetan-induced thrombocytopenia where We stopped cefuroxime and repeated the full on September 24, 2021 by guest. Protected copyright. potent IgG-cefotetan-dependent antiplatelet blood count days later, finding that the platelet antibodies were detected in the patient's count had risen to 164 x 109/l. Nine days later serum.2 An animal model in the dog has also it was 325 x 109/1. The diagnosis was now a been described.3 severe depressive episode. A course of electro- convulsive therapy was started on the day after Case report A 77-year-old man known to suffer from mild Alzheimer's disease and recurrent depressive Side-effects of cefuroxime disorder was admitted with a 10-day history of increasing anxiety and agitation and worsening * hypersensitivity reactions depression. Examination revealed marked psy- * overgrowth of susceptible organisms * gastrointestinal disturbance chomotor agitation, perseverations and verbal * pseudomembranous colitis stereotypies. His cognitive functioning had * haematological parameters altered, including Department of deteriorated. He appeared physically ill with a decreased haemoglobin concentration, Psychiatry, Farnham fluctuating conscious level, tachycardia, ta- leucopenia, neutropenia Road Hospital, chypnoea and profuse sweating. He remained * positive Coombs test Guildford, Surrey apyrexial. * transient rise in liver function tests GU2 5LX, UK * pain at injection site P Aitken We diagnosed acute confusional state (delir- * very rare reports of thrombocytopenia SMN Zaidi ium ICD 10) superimposed on mild dementia precipitating a relapse of his depressive dis- Accepted 7 February 1996 order. We started haloperidol 5 mg bid on Box 1 758 Aitken, Zaidi Drugs implicated in immune Learning points thrombocytopenial Postgrad Med J: first published as 10.1136/pgmj.72.854.757 on 1 December 1996. Downloaded from * severe depressive episode can be difficult to Drug-dependent platelet-activating IgG (Fc receptor differentiate from organic pathology, especially dependent) in the elderly Unfractionated heparin, low molecular weight * many drugs are implicated in immune heparin, pentosan polysulphate, chondroitin thrombocytopenia, including many commonly sulphate. prescribed antibiotics * cefuroxime appears capable of producing a Drug-dependent increase in platelet-associated moderately severe thrombocytopenia IgG (Fab-dependent, Fc-independent, binding to glycoproteins IIb/IIIa or IblIX or both) Quinine, quinidine, vancomycin. Box 3 Drug-dependent increase in platelet-associated IgG (glycoprotein localisation unknown) Ampicillin, cephamandole, chlorpheniramine, stopping cefuroxime. He received four treat- cimetidine, diazepam, digoxin, gold, ments over two weeks; the haloperidol was hydrochlorthiazide, mianserin, 'sulfa' antibiotics, then reduced and stopped. He made a com- penicillin, ranitidine, rifampicin. plete recovery. Probable drug-induced thrombocytopenia (established by drug rechallenge or drug-dependent Discussion phase 1 assay) Acetaminophen, acetazolamide, actinomycin, Early investigative results suggested a staphy- allyl-isopropyl-acetylcarbamide, alprenolol, lococcal infection which was treated blind with aminoglutethimide, amiodarone, antazoline, cefuroxime 750 mg tid parenterally for five aspirin, carbamazepine, cephalexin, cephalothin, chlorthalidone, chlorthiazide, danazol, days. When the platelet count was noted to be desferrioxamine, desipramine, falling, other causes of thrombocytopenia were difluoromethylornithine, digitoxin, diflunisal, considered. After the final microbiology report, diphenylhydantoin, ethchlorvynol, furosemide, an infective aetiology was less likely. Through- gentamycin, imipramine, iopanoic acid, out treatment with cefuroxime the clinical state levamisole, alpha-interferon, beta-inteferon, remained unchanged, as did the neutrophilia. lidocaine, mepabromate, methicillin, minoxidil, morphine, methyldopa, nomifensine, novobiocin, This made it less likely that the patient had an paraaminosalicylic acid, phenyl butazone, undiagnosed infection that responded to ce- oxprenolol, naladixic acid, pirenzipine, furoxime. The only concomitant drug therapy procainamide, spironolactone, stibophen. was haloperidol 5 mg bid, not known to cause thrombocytopenia. In the absence of a proven Possible drug-induced thrombocytopenia (no microbiological cause and with resolution on rechallenge or in vitro testing) Apalcillin, butobarbitone, captopril, stopping the cefuroxime we believe that the chlordiazepoxide/clidinium bromide, thrombocytopenia can only have been due to chlorpropamide, clinoril, clonazepam, the cephalosporin. We considered it unethical diatrizoate, diazoxide, etretinate, fenoprofen, to submit him to rechallenge. glibenclamide, heroin, indomethacin, isoniazid, Review of the literature reports cephalospor- http://pmj.bmj.com/ levodopa, lincomycin, nitroprusside, in and penicillin antibiotics to be implicated in oxyphenbutazone, oxytetracycline, pentamidine, piroxicam, primidone, sulindac, ticlopidine, immune thrombocytopenia by a drug-depen- tobramycin, tolbutamide, tolmetin, toluene. dent increase in platelet-associated IgG. We believe this case to be the first to implicate Drugs with high incidence of mild thrombocytopenia cefuroxime directly. and positive direct platelet-associated IgG Valproic acid, amrinone. on September 24, 2021 by guest. Protected copyright. Drug-induced lupus anticoagulant syndrome and thromboembolism Procainamide. Drug-induced haemolytic-uraemic syndrome Quinine, proguanil, penicillin, ampicillin. Drug-induced immune haemolytic anaemia with thrombocytopenia Diclofenac, doxepin, glafenine, nomifensine. Box 2 1 Hull RL, Brandon D. Thrombocytopenia possibly caused 4 ABPI Data Sheet Compendium: Cefuroxime, 1995-6, by structurally related third generation cephalosporins. p 656. DICP 1991; 25: 135-6. 5 Bloom AL, Forbes CD, Thomas DP, Tiddenham EGD, 2 Christie DJ, Lennon SS, Drew RL, Swinehart CD. (editors). Acquired platelet disorders: drugs implicated in Cefotetan-induced immunologic thrombocytopenia. Br J immune thrombocytopaenia: haemostasis and thrombosis, Haematol 1988; 70: 423-6. Vol 2. London: Churchill Livingstone, 1994; pp 776-8. 3 Bloom JC, Lewis HB, Sellers TS, Deldar A. The hematologic effects of cefonicid and cefazedone in the dog: a potential model of cephalosporin hematoxicity in man. Toxicol Appl Pharmacol 1987; 90: 135 - 42..