Atorvastatin-induced severe thrombocytopenia.(Research Letters)Author/s: Maria Luisa Gonzalez-Ponte Atorvastatin, a new 3-hydroxy-3methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor, has been approved by the US Food and Drug Administration for treatment of primary hypercholesterolaemia and mixed dyslipidaemia.1 Like other statins, atorvastatin acts by inhibiting HMG-CoA reductase, which results in decreased serum concentrations of LDL cholesterol and, especially, triglycerides, more than the decrease caused by other HMG-CoA reductase inhibitors. The adverse-effect profile is similar to that of other statins, with no adverse events previously not reported for other statins.2 The most frequent adverse effects are constipation, flatulence, dyspepsia, abdominal pain, headache, and myalgia. Insomnia and minor rises in aminotransferase activity have also been reported.1-3 No cases of suspected statin-induced thrombocytopenia have been reported. We describe a patient who developed severe thrombocytopenia while on atorvastatin. A man aged 46 years was admitted in January, 1998, because of thrombocytopenic purpura. He had hypercholesterolaemia and hyperuricaemia, and had been given irregularly simvastatin, allopurinol, and colchicine in the previous year. In July, 1997, he underwent aortic valvular replacement and acenocoumarol and atenolol were started, as were allopurinol 300 mg per day and colchicine 1 mg per day. Serial blood analysis showed stable platelet counts. 2 months before admission, the patient had started atorvastatin 10 mg per day because of inadequate control of hypercholesterolaemia. Physical examination was unremarkable apart from widespread purpura, with a platelet count of 33109/L. International normalised ratio was 3.8 because of acenocoumarol, but the rest of coagulation results were normal. Atorvastatin and colchicine were discontinued. The bone-marrow assessment showed a normal haemopoiesis with an increased number of megakaryocytes. The patient was given packed platelets, intravenous methylprednisolone 1 mg/kg, and g-globulin 400 mg/kg for 5 days. His platelet count increased to 71x109/L, and the patient was discharged with acenocoumarol, allopurinol, atenolol, ranitidine, and prednisone. The next day, the patient reinstituted by himself atorvastatin and colchicine, and he was readmitted to the hospital 4 days later because of diseminated petechiae. His platelet count had fallen to 53109/L. Atorvastatin, acenocoumarol, allopurinol, and colchicine were discontinued. He was given another 5-day course of intravenous methylprednisolone and g-globulin, and platelets increased to 36x109/L. He was discharged with acenocoumarol, atenolol, ranitidine, and prednisone. His platelet count was within the normal range 1 month later, and remained normal after corticosteroids were withdrawn. Colchicine has been reinstituted in March because acute gouty arthritis and platelet count remains normal. Although it is impossible to exclude definitively allopurinol as an alternative causal agent, since there has not been rechallenge, various factors, such as the temporal relation between the initiation of atorvastatin and the onset of thrombocytopenia,4 in addition to the effects of the discontinuation and resumption of the drugs, are highly suggestive of atorvastatin-induced immune thrombocytopenia. Chemically atorvastatin, a single stereoisomer of a pyrrole derivative, is different from other statins.1,3 The fact that thrombocytopenia was not caused in this patient while on simvastatin suggests that this adverse reaction was not an effect of HMG-CoA-reductase inhibition, but an idiosyncratic reaction to atorvastatin or to one of its metabolites. Consequently, for a patient with such a reaction to atorvastatin and for whom the lipid-lowering effects of an HMG-CoA-reductase inhibitor are necessary, other statins could be cautiously used. |