Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ticlopidine, an adenosine diphosphate receptor blocker, is widely used to prevent subacute stent thrombosis after percutaneous coronary intervention. Along with neutropenia and thrombotic thrombocytopenic purpura, cholestatic hepatitis is one of the most serious potential side-effects of ticlopidine therapy. Four patients with prolonged jaundice after ticlopidine therapy, including one fatal case, are presented. Alternative antithrombotic therapy for subsequent percutaneous coronary intervention is also described. Clopidogrel therapy was found to be safe and effective in two patients with a history of ticlopidine-related cholestatic hepatitis.
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PMID:Prolonged jaundice following percutaneous coronary intervention and ticlopidine therapy. 1186 96

In patients with transient ischemic attack (TIA) or ischemic stroke of noncardiac origin, antiplatelet drugs are able to decrease the risk of stroke by 11% to 15%, and decrease the risk of stroke, myocardial infarction (MI), and vascular death by 15% to 22%. Aspirin leads to a moderate but significant reduction of stroke, MI, and vascular death in patients with TIA and ischemic stroke. Low doses are as effective as high doses, but are better tolerated in terms of gastrointestinal side effects. The recommended aspirin dose, therefore, is between 50 and 325 mg. Bleeding complications are not dose-dependent, and also occur with the lowest doses. The combination of aspirin (25 mg twice daily) with slow-release dipyridamole (200 mg twice daily) is superior compared with aspirin alone for stroke prevention. Ticlopidine is effective in secondary stroke prevention in patients with TIA and stroke. For some end points, it is superior to aspirin. Due to its side-effect profile (neutropenia, thrombotic thrombocytopenic purpura ), ticlopidine should be given to patients who are intolerant of aspirin. Prospective trials have not indicated whether ticlopidine is suggested for patients who have recurrent cerebrovascular events while on aspirin. Clopidogrel has a better safety profile than ticlopidine. Although not investigated in patients with TIA, clopidogrel should also be effective in these patients assuming the same pathophysiology than in patients with stroke. Clopidogrel is second-line treatment in patients intolerant for aspirin, and first-line treatment for patients with stroke and peripheral arterial disease or MI. A frequent clinical problem is patients who are already on aspirin because of coronary heart disease or a prior cerebral ischemic event, and then suffer a first or recurrent TIA or stroke. No single clinical trial has investigated this problem. Therefore, recommendations are not evidence-based. Possible strategies include the following: continue aspirin, add dipyridamole, add clopidogrel, switch to ticlopidine or clopidogrel, or switch to anticoagulation with an International Normalized Ratio (INR) of 2.0 to 3.0. The combination of low-dose warfarin and aspirin was never studied in the secondary prevention of stroke. In patients with a cardiac source of embolism, anticoagulation is recommended with an INR of 2.0 to 3.0. At the present time, anticoagulation with an INR between 3.0 and 4.5 cannot be recommended for patients with noncardiac TIA or stroke. Anticoagulation with an INR between 3.0 and 4.5 carries a high bleeding risk. Whether anticoagulation with lower INR is safe and effective is not yet known. Treatment of vascular risk factors should also be performed in secondary stroke prevention.
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PMID:Antithrombotic Secondary Prevention After Stroke. 1219 15

The thienopyridines, ticlopidine and clopidogrel, are antiplatelet drugs. They are prodrugs and are metabolised in the liver to active metabolites that are non-competitive antagonists of the platelet adenosine diphosphate receptor, P2Y12. Inhibition of platelet aggregation by these drugs is delayed until 24-48 h after administration, with maximal inhibition achieved after 3-5 days. Recovery of platelet function after drug withdrawal is slow (7-14 days). Ticlopidine and clopidogrel are effective in preventing atherothrombotic events in cardiovascular, cerebrovascular and peripheral vascular disease. Gastrointestinal side effects and skin rashes are common. However, neutropenia and thrombotic thrombocytopenic purpura are significant and sometimes fatal adverse effects of ticlopidine. Clopidogrel appears to offer several advantages over ticlopidine: a more rapid onset of action and a lower incidence of neutropenia and thrombotic thrombocytopenic purpura.A combination of clopidogrel and aspirin has become standard for antithrombotic therapy in cardiovascular disease. The anaesthetic considerations of patients taking the thienopyridine compounds are discussed.
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PMID:The thienopyridine derivatives (platelet adenosine diphosphate receptor antagonists), pharmacology and clinical developments. 1284 38

Clopidogrel, an ideal treatment for prevention of subacute stent thrombosis, may not be feasible to use in every patient. Ticlopidine (plus aspirin) is a very good alternative, although the risks of life threatening neutropenia should mandate regular monitoring of blood counts. It is proposed that patients undergoing angioplasty and stenting should carry a warning card in an effort to make the public and general practitioners aware that antiplatelet treatment after angioplasty plays an important part in ensuring successful outcome.
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PMID:Clopidogrel induced urticarial rash in a patient with left main stem percutaneous coronary intervention: management issues. 1496 75

Patients experiencing stroke or transient ischemic attack (TIA) are at high risk for recurrent (secondary) strokes, which comprise 29% of all strokes in the United States. Current recommendations for prevention of secondary stroke from the American College of Chest Physicians (ACCP) call for the broad use of platelet antiaggregation (antiplatelet) agents for patients with a history of noncardioembolic stroke or TIA. Five agents--aspirin, ticlopidine, clopidogrel, extended-release dipyridamole (ER-DP), and triflusal--have demonstrated efficacy in large-scale clinical studies in the prevention of recurrent vascular events and/or stroke in patients with a history of stroke. The results of the following studies are reviewed and compared: the Swedish Aspirin Low-Dose Trial (SALT), the United Kingdom Transient Ischaemic Attack (UK-TIA) Aspirin Trial, Dutch Transient Ischemic Attack (Dutch TIA) study (aspirin), the Canadian American Ticlopidine Study (CATS), the Ticlopidine Aspirin Stroke Study (TASS), the African American Antiplatelet Stroke Prevention Study (AAASPS) (ticlopidine), the Clopidogrel versus Aspirin in Patients at Risk of Recurrent Ischemic Events (CAPRIE) trial, the Management of Atherothrombosis With Clopidogrel in High-Risk Patients study (MATCH) (clopidogrel), the second European Stroke Prevention Study (ESPS2) (aspirin plus ER-DP), and the Triflusal versus Aspirin in Cerebral Infarction Prevention (TACIP) study. In comparative monotherapy studies of patients with previous stroke, ticlopidine demonstrates statistically significant improved efficacy over aspirin, and clopidogrel demonstrates nonsignificant slight improvement over aspirin for the prevention of ischemic cardiac and cerebrovascular events; however, the adverse event profile of ticlopidine (including rash, diarrhea, and neutropenia) will probably limit its long-term use. Among combination approaches, only aspirin plus ER-DP has demonstrated statistically significant, clinically meaningful additive benefit over monotherapy with each agent. Clopidogrel plus aspirin did not significantly improve preventive efficacy and increased the risk of serious side effects, including life-threatening bleeding episodes. The 15,500-patient PRoFESS (the Prevention Regimen for Effectively Avoiding Second Strokes) study, with results expected in 2008, will directly compare aspirin plus ER-DP with clopidogrel monotherapy for the prevention of recurrent stroke and should provide statistically robust estimates of comparative efficacy for the development of improved recommendations.
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PMID:Review of antiplatelet therapy in secondary prevention of cerebrovascular events: a need for direct comparisons between antiplatelet agents. 1621 Dec 3

Large multi-center clinical trials have indicated significant clinical benefits for patients with atherosclerotic vascular diseases receiving clopidogrel therapy. Clopidogrel efficacy has been proven in cardiac and extracardiac vascular diseases. Thus, the popularity of using clopidogrel is likely to increase in the near future. However, clopidogrel therapy may be accompanied by rare life-threatening adverse events. An increasing body of evidence show that clopidogrel is associated with aplastic anemia, thrombocytopenia and neutropenia. Interestingly, the majority of multi-center clinical trials have reported bleeding as the major side effect of clopidogrel therapy and failed to detect the actual incidence of other serious hematological side effects. Highlighting the potential adverse events of clopidogrel therapy in large clinical trials is therefore essential if we are to learn any lessons from having ignored the reporting of serious adverse side effects of a closely related drug (ticlopidine) in its large clinical trials.
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PMID:Non-bleeding side effects of clopidogrel: have large multi-center clinical trials underestimated their incidence? 1691 20

Clopidogrel is used as a frontline antiplatelet agent in patients with coronary artery disease, cerebrovascular disease, and peripheral vascular disease. Hematologic complications and bleeding have been the most feared outcome of antithrombotic and antiplatelet agents. Among the thienopyridines, clopidogrel is considered to be a safer alternative to ticlopidine due to its decreased incidence of hematologic adverse effects. Although thrombotic thrombocytopenia purpura is the most reported hematologic adverse effect of clopidogrel; neutropenia, acquired hemophilia, isolated thrombocytopenia or idiopathic immune thrombocytopenia, and thrombotic thrombocytopenia purpura with hemolytic uremic syndrome are other rare yet recognized hematologic adverse effects of clopidogrel. Patients treated with clopidogrel should be carefully monitored for hematologic adverse effects especially in the first 2 to 3 months after initiation of therapy. Early recognition and prompt initiation of treatment can be life saving in patients who have hematologic adverse effects to clopidogrel. We have drafted this review by performing literature search using Medline, Pubmed, and EMBASE search engine with relevant search words for all reported hematologic adverse effects and manifestations of clopidogrel and their management.
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PMID:Hematologic adverse effects of clopidogrel. 1730 78

The antiplatelet drug clopidogrel is an oral thienopyridine derivative that has been extensively used for the treatment and secondary prevention of a variety of cardiovascular diseases. Although clopidogrel is well tolerated by most patients, rare but serious hypersensitivity reactions have been documented, including cutaneous reactions and angioedema. An alternative thienopyridine that may be substituted for clopidogrel is ticlopidine; however, deleterious side effects from ticlopidine may occur, including diarrhea, neutropenia, and thrombocytopenia purpura, and cross-reactivity has been documented between these two thienopyridines. In cases of bare-metal stent deployment, cilostazol may be a safe and effective alternative; however, limited therapeutic data are available. In such cases, providers may need to administer a clopidogrel desensitization protocol; three clopidogrel desensitization protocols have been published. We describe a 58-year-old man who developed a generalized diffuse rash along his abdomen within 2 weeks of exposure to clopidogrel after drug-eluting stent placement. Clopidogrel was discontinued, and ticlopidine was begun. The rash resolved within 3 days of clopidogrel discontinuation. Using the Naranjo adverse drug reaction probability scale, we determined that the probability of clopidogrel causing the rash was probable (score of 8). Ticlopidine was subsequently discontinued due to severe diarrhea. Because of the patient's implanted stent and high risk for possible thrombosis, an 8-hour clopidogrel desensitization protocol was devised and successfully used in this patient, who continued to receive clopidogrel over the next year without rash recurrence. Based on our experience and the literature reviewed, administration of a clopidogrel desensitization protocol in patients with a history of isolated cutaneous hypersensitivity reactions, including angioedema, to clopidogrel can be a safe therapeutic alternative to ticlopidine or cilostazol.
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PMID:Clopidogrel desensitization: case report and review of published protocols. 1822 71

Clopidogrel has mostly replaced the use of ticlopidine due to its more favourable hematologic adverse event profile. Prasugrel is the newest thienopyridine approved for use in Canada. This case describes a patient who was diagnosed with an acute coronary syndrome and treated with bare metal stenting of his coronary artery. He was discharged home on clopidogrel therapy. Two weeks later he presented with severe neutropenia. Clopidogrel was discontinued and prasugrel was initiated. Neutrophil count gradually increased and returned to normal. In patients with neutropenia associated with clopidogrel therapy, prasugrel may be considered as an alternative.
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PMID:Prasugrel as an alternative for clopidogrel-associated neutropenia. 2179 65

Dual antiplatelet therapy with aspirin plus thienopyridines has become the standard treatment of patients undergoing coronary stenting. Clopidogrel has mostly replaced the use of ticlopidine due to its more favourable adverse event profile. However, also the use of clopidogrel is not without side effects. Clopidogrel major adverse events are represented by marrow suppression, manifesting with aplastic anaemia, thrombocytopenia and neutropenia. When clopidogrel toxicity occurs, there are few and unsubstantiated alternative treatments and thus, in these cases, medical decisions may be very difficult. We report a case of clopidogrel-induced bone marrow toxicity manifesting with severe neutropenia in a patient treated with multiple coronary stents and provide suggestions for an alternative treatment.
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PMID:Clopidogrel-induced neutropenia after coronary stenting: is cilostazol a good alternative? 2186 Jul 99


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