Neutropenia ticlopidine

Ticlopidine is slightly more beneficial in stroke prevention than aspirin in both men and women.31,32 The usual recommended dosage is 250 mg orally twice daily. Ticlopidine is costly, and side effects include bone marrow suppression, rash, diarrhea, and an increased cholesterol level. Neutropenia is seen in approximately 2% of patients. Thrombotic thrombocytopenic... 

Ticlopidine is associated with neutropenia that requires frequent monitoring of the complete blood cell count during the first 3 months of use. For this reason, clopidogrel is the preferred thienopyridine for ACS and PCI patients. 

Ticlopidine can cause life-threatening hematological adverse reactions, including neutropenia/agranulocytosis and thrombotic thrombocytopenic purpura (TTP). Neutropenia/agranulocytosis Neutropenia defined as an absolute neutrophil count (ANC) less than 1,200 neutrophils/mm occurred in 50 of 2048 (2.4%) stroke patients who received ticlopidine in clinical trials. Neutropenia is calculated as follows ANC = WBC x % neutrophils. In 17 patients (0.8%) the neutrophil count was less than 450/mm. ... 

Because ticlopidine is associated with a risk of life-threatening blood dyscrasias including TTP and neutropenia/agranulocytosis (see Warnings), reserve for patients who are intolerant or allergic to aspirin therapy or who have failed aspirin therapy. 

Adverse reactions were relatively frequent, with more than 50% of patients reporting at least one. Most involved the Gl tract. Most adverse effects are mild, but 21% of patients discontinued therapy because of an adverse event, principally diarrhea, rash, nausea, vomiting, Gl pain, and neutropenia. Most adverse effects occur early in the course of treatment, but a new onset of adverse effects can occur after several months. Ticlopidine has been associated with a number of bleeding complications such as ecchymosis, epistaxis, hematuria, conjunctival hemorrhage,... 

Clopidogrel has fewer adverse effects than ticlopidine and is rarely associated with neutropenia. Thrombotic thrombocytopenic purpura associated with clopidogrel has been reported. Because of its superior side effect profile and dosing requirements, clopidogrel is preferred over ticlopidine. The antithrombotic effects of clopidogrel are dose-dependent within 5 hours after an oral loading dose of 300 mg, 80% of platelet activity will be inhibited. The maintenance dose of clopidogrel is 75 mg/d, which achieves maximum platelet inhibition. The duration of the antiplatelet effect is 7-10 days. 

In addition to the risk of bleeding, which will be detailed in the different studies, thienopyridines are able to cause skin disorders (rashes or prurit) and gastrointestinal disorders (diarrhea). In the CLASSICS study, these side effects were observed in 8.2% of patients treated with ticlopidine and in 3.5% of those taking clopidogrel treatment. The most serious problem was related to hematologic disorders neutropenia or thrombocytopenia. These disorders are much less frequent with clopidogrel than with ticlopidine 0.04% of neutropenia in the CAPRIE study and 0.05% in the CURE trial, Thrombotic thrombocytopenic purpura are exceptional one for 200,000 patients. 

Various other hematological complications have been observed during ticlopidine treatment (5). They include neutropenia, agranulocytosis, thrombocytopenia, aplastic anemia, pancytopenia, and thrombotic thrombocytopenic purpura (6). These reactions are potentially severe and some are fatal. Major bleeding is rare. Among 188 cases of hematological comphcations associated with ticlopidine and reported to the US Food and Drug Administration, 36 (19%) resulted in death (7). 

Haushofer A, Halbmayer WM, Prachar H. Neutropenia with ticlopidine plus aspirin. Lancet 1997 349(9050) 474-5. 

Farver DK, Hansen LA. Delayed neutropenia with ticlopidine. Ann Pharmacother 1994 28(12) 1344-6. 

Gur H, Wartenfeld R, Tanne D, Solomon F, Sidi Y. Ticlopidine-induced severe neutropenia. Postgrad Med J 1998 74(868) 126-7. 

The efficacy of clopidogrel as an antiplatelet agent in atherothrombotic disorders was demonstrated in the CAPRIE trial. In this study of more than 19,000 patients with a history of either myocardial infarction (MI), stroke, or peripheral arterial disease (PAD), clopidogrel 75 mg/day was compared with aspirin 325 mg/day for its ability to decrease MI, stroke, or cardiovascular death. In the final analysis, clopidogrel was slightly (8% relative risk reduction [RRR]) more effective than aspirin (p =. 043) and had a similar incidence of adverse effects. It is not associated with the blood dyscrasias (neutropenia) common with its congener, ticlopidine, and is used widely in patients with atherosclerosis. 

Ticlopidine is a thienopyridine antiplatelet agent, similar in structure and mechanism of action to clopidogrel. It has been shown to reduce the risk of stroke by 30% compared with placebo and by 21% compared with aspirin 325 mg/day inpatients at risk. The use of ticlopidine has been severely restricted by its side-effect profile, however. It causes bone marrow suppression, rash, diarrhea, and elevation of the serum cholesterol concentration. Neutropenia occurs in up to 2% of patients and generally is reversible. More problematic, however, is the increased risk of aplastic anemia and thrombotic thrombocytopenic purpura. Ticlopidine 250 mg twice daily is stiU available as an alternative in patients who fail or are intolerant of other therapies but is rarely needed. 

If the patient is unable to tolerate the drug identified in Question 6, he may be treated with clopidogrel. Relative to ticlopidine, clopidogrel (A) Has a shorter duration of action Is less likely to cause neutropenia Is more likely to induce antiplatelet antibodies Is more likely to precipitate serious bleeding Will have a greater antiplatelet effect... 

Ticlopidine and clopidogrel have similar mechanisms of action and therapeutic efficacy. The key difference between these two drugs is that clopidogrel is less likely to cause neutropenia and therefore does not require routine monitoring of blood cell counts during therapy. The answer is (B). 

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