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Nonfatal aplastic anemia associated with clopidogrel/Klopidogrel ile iliskili olumcul olmayan aplastik anemi.

Thienopyridines inhibit the adenosine 5'-diphosphate P2Y12 receptor on platelets. These drugs reduce the overall rate of thromboembolic events in patients with atherosclerotic vascular disease after stent implantation. Ticlopidine is a first-generation thienopyridine. The use of ticlopidine has two major limitations, which are its safety profile and its inability to induce platelet inhibition rapidly. Thus, clopidogrel, a second-generation thienopyridine, has largely replaced ticlopidine. Clopidogrel therapy may also be accompanied by rare life-threatening side effects (1). Clopidogrel may be found to be associated with severe bone marrow suppression manifested as bone marrow failure (2), aplastic anemia, thrombocytopenia, neutropenia. We present a case of aplastic anemia caused by clopidogrel.

A 55-year-old man with acute coronary syndrome underwent bare metal stent implantation to target lesion in the circumflex coronary artery on May, 2008. He was started on clopidogrel (300 mg loading followed by 75 mg daily) for at least 12 months. His baseline hematologic findings were normal at that time. Eleven months after the introduction of clopidogrel, he was evaluated in our out-patient cardiology clinic because of mainly fatigue. He denied angina. At last, on his clinical and laboratory assessment, hematologic findings revealed severe pancytopenia. His hemoglobin level was 8.4 g/dL, erythrocyte count--2.4 x [10.sup.l2]/L, white-cell count--2.8 x [10.sup.9]/L (neutrophils 62%, lymphocytes 31%, monocytes 6%, and eosinophils 1%), and platelets count--31 x [10.sup.9]/L. Bone marrow examination findings demonstrated severe hypoplasia of all three lineages without fibrosis. Results of cytogenetic analysis were normal (46, XY with no structural anomaly) and a Ham test was negative. There was no evidence of autoimmune disorders, hepatitis, parvovirus infection or other viral infections and other drugs use such as angiotensin-converting enzyme inhibitors. The serum levels of vitamin B12 and folic acid were normal. Ultrasound examination did not disclose splenomegaly or lymphadenopathy. Aplastic anemia was diagnosed, and resolved fourteen days after stopping clopidogrel. His symptoms were rapidly relieved.

The incidence of thrombocytopenia and neutropenia induced by clopidogrel was reported to be 0.26 and 0.10%, respectively in CAPRIE study (3). The mechanism of aplastic anemia induced by clopidogrel is not well understood (possibilities include cumulative toxicity or idiosyncratic reaction) (4). In a previous report, it was suggested that aplastic anemia occurred within 5 months of starting clopidogrel (5). In our case, aplastic anemia occurred within 11 months of starting clopidogrel.

As a result, clopidogrel may be a potential cause of aplastic anemia irrespective ofthe duration of treatment, though rarely seen. Therefore, careful clinical and hematological monitoring should be carried out in the course of treatment with clopidogrel.

doi: 10.5152/akd.2010.075

References

(1.) CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348:1329-39.

(2.) Chemnitz J, Sohngen D, Schulz A, Diehl V, Scheid C. Fatal toxic bone marrow failure associated with clopidogrel. Eur J Haematol 2003; 71:473-4.

(3.) Harker LA, Boissel JR Pilgrim AJ, Gent M. Comparative safety and tolerability of clopidogrel and aspirin: results from CAPRIE. Clopidogrel versus aspirin in patients at risk of ischemic events. Drug Saf 1999; 21: 32535.

(4.) Andres E, Perrin AE, Alt M, Goichot B, Schlienger JL. Febrile pancytopenia associated with clopidogrel. Arch Intern Med 2001; 161:125.

(5.) Trivier JM, Caron J, Mathieu M, Cambiar N, Rose C. Fatal aplastic anemia associated with clopidogrel. Lancet 2001; 357: 446.

Address for Correspondence / Yazisma adresi: Dr. Omer Uz Department of Cardiology, Haydarpasa Giilhane Military Medical School, Istanbul, Turkey. Phone: +90 216 542 34 65 Fax: +90 216 348 78 80 E-mail: homeruz@yahoo.com

Omer Uz, Ejder Kardesoglu, Mustafa Aparci, Omer Yiginer, Zafer Isilak, Namik Ozmen

From Department of Cardiology, Haydarpasa Giilhane Military Medical School, Istanbul, Turkey
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Article Details
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Title Annotation:Letters to the Editor/Editore Mektuplar
Author:Uz, Omer; Kardesoglu, Ejder; Aparci, Mustafa; Yiginer, Omer; Isilak, Zafer; Ozmen, Namik
Publication:The Anatolian Journal of Cardiology (Anadolu Kardiyoloji Dergisi)
Article Type:Letter to the editor
Date:Jun 1, 2010
Words:622
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