Clinique d'Hématologie and
1 Département d'Immunologie, Hématologie et Transfusion, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
SIR, Rofecoxib is a selective cyclooxygenase (COX)-2 inhibitor that has little or no effect on the COX-1 isoenzyme at doses up to 1000 mg/day. Compared with traditional non-steroidal anti-inflammatory drug (NSAID) therapy, rofecoxib has a significantly lower incidence of gastrointestinal adverse events. The most common adverse events are nausea, dizziness and headache [1]. We report the first case of thrombocytopenia after rofecoxib treatment.
A 66-yr-old man was referred to our hospital on 14 November 2000 with a disseminated petechial rash and epistaxis. His medical history included psoriasis. He did not take any medication. The patient had visited his family physician 7 days earlier for pain in the shoulders and the hips that he had had for 2 months, and was placed on rofecoxib 12.5 mg/day orally. The platelet count at the onset of treatment was normal. Blood samples disclosed only moderate signs of inflammation. Rofecoxib was taken from 7 November to 11 November 2000 and was stopped spontaneously by the patient because of the occurrence of purpura. The patient did not take non-prescription drugs, such as acetaminophen or remedies including quinine. After epistaxis and bleeding in the mouth had occurred, the patient was hospitalized. Clinical examination showed haemorrhagic bullae in the mouth. No lymphadenopathy or hepatosplenomegaly was observed. Blood tests revealed a white blood cell count of 11x103/mm3, haemoglobin 15.8 g/dl and a platelet count of 1x103/mm3. Coagulation studies were normal. Renal and liver function tests were normal. There was an important inflammatory syndrome. Autoimmune serologies were negative. A platelet antibody test of the serum using the MAIPA (monoclonal antibody immobilization of platelet antigens) test was negative. Direct tests on the platelets could not be done because of the severe thrombocytopenia. There was no serological evidence of recent viral infection. A bone marrow aspirate was normal. Ultrasound examination of the spleen was normal. Rofecoxib was suspected to be the causative agent. Despite therapy with methyl prednisone 1 mg/kg/day and human immunoglobulin 1 g/kg administered on days 1 and 3, the patient presented severe melena on day 4 of hospitalization, when his platelet count was still 1x103/mm3. Gastroduodenoscopy disclosed severe grade 3 oesophagitis. The patient was transferred to the intensive care unit, where a course of five plasmaphereses with plasma exchange was performed from day 4 until day 8 of hospitalization. The platelet count increased to 4x103/mm3 on day 8 and 262x103/mm3 on day 10 of hospitalization. Complaints of arthralgias and the biological signs of inflammation disappeared rapidly. Methyl prednisone was progressively reduced. The platelet count was normal 21 months after rofecoxib had been discontinued and no evidence of other causes of thrombocytopenia became clinically evident. Complaints of pain in the shoulders and the hips accompanied by an inflammatory syndrome reappeared when corticoids were stopped. A diagnosis of polymyalgia rheumatica was made.
Thrombocytopenia is a rare but classic complication of therapy with NSAIDs. NSAIDs accounted for 49 of 309 (15.8%) cases of drug-induced thrombocytopenia reported to the Danish Committee on Adverse Drug Reactions between 1968 and the end of 1991 [2] and for eight of 247 (3.2%) cases of definite or probable `drug-induced thrombocytopenia' in a systematic review of published case reports [3].
As no data on assays for drug-dependent antiplatelet antibodies are available, other criteria are needed in order to make the diagnosis of drug-induced thrombocytopenia. George et al. [3] proposed criteria to evaluate evidence for a causal relationship of drugs to thrombocytopenia. In the present case, therapy with rofecoxib preceded thrombocytopenia, recovery from thrombocytopenia was complete and sustained after discontinuation of rofecoxib, rofecoxib was the only drug used before the onset of the thrombocytopenia, and other causes of thrombocytopenia were excluded. According to the criteria of George et al., the causal relationship between rofecoxib and thrombocytopenia was thus probable. The severity of the thrombocytopenia prevented us from rechallenging the patient with rofecoxib to establish a definite relationship. The primary treatment for drug-induced thrombocytopenia is to discontinue the suspected causative agent. As in this case, patients experiencing life-threatening bleeding may benefit from intravenous immunoglobulin therapy, plasmapheresis or platelet transfusions [4]. Although corticosteroids seem inefficient, it is recommended that severe symptomatic cases of drug-induced thrombocytopenia should be treated as idiopathic thrombocytopenic purpura because of the difficult initial differentiation between the two conditions [2]. In conclusion, we report the first case of severe life-threatening rofecoxib-induced thrombocytopenia.
Notes
Correspondence to: A. Kentos, Clinique d'Hématologie, ULB-Hôpital Erasme, 808, Route de Lennik, B-1070 Bruxelles, Belgium. E-mail: akentos{at}ulb.ac.be
References
|