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)

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

Platelets play a critical role in the pathogenesis of atherothrombotic processes and inhibition of platelet aggregation by antiplatelet therapy is essential and really important in the acute coronary syndromes or in the setting of percutaneous coronary intervention. The first family of adenosine diphosphate P2Y12 receptors inhibiting drug is represented by thienopyridines and among these ticlopidine was the first approved by Food and Drug Administration; actually its use is discouraged because of its potential side effects (neutropenia, anemia, gastrointestinal distress and thrombotic thrombocytopenic purpura). The second generation of thienopyridines is represented by clopidogrel that has replaced ticlopidine in the clinical practice; clopidogrel has the largest clinical experience. Prasugrel represents the third generation. It inhibits platelet aggregation by irreversibly blocking the adenosine diphosphate P2Y12 receptor. Ticagrelor, Cangrelor and Enilogrel represent the last generation of thienopyridines. This review is focused on the effects of adenosine diphosphate P2Y12 inhibitors.
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PMID:P2Y12 inhibitors: pharmacologic mechanism and clinical relevance. 2296 29

Aspirin in combination with platelet P2Y12 receptor blocker has become the mainstay antiplatelet treatment strategy for the prevention of stent thrombosis. Ticlopidine was the first widely used P2Y12 receptor blockers, but clopidogrel has mostly replaced the use of ticlopidine due to its more favorable adverse event profile on bone marrow. However, when clopidogrel induced bone marrow toxicity occurs, little is known about the efficacy and safety of alternative treatments, and thus, in these cases, medical decisions may be very difficult. We report a case of clopidogrel-induced severe neutropenia in a patient treated with coronary stent and safety of alternative treatment with ticagrelor.
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PMID:Ticagrelor as an alternative in clopidogrel-associated neutropenia. 2443 37

Clopidogrel is a second generation of thienopyridine, which has antiplatelet effect by inhibiting P2Y12 receptor. Hematologic adverse effect is very uncommon during clopidogrel use, but some cases of clopidogrel-associated neutropenia were reported in the past decade. Until now, there was no summary data to delineate the clinical course and safe alternatives of this event. We report 2 cases of clopidogrel-associated neutropenia and review other 10 case reports from 2000 to 2014. The median onset of neutropenia was 22 days, and the recovery time was 4 days after receiving granulocyte-colony-stimulating factor. Bone marrow studies in 6 cases all showed hypocellular or toxic damage. Six cases used cilostazol, prasugrel, or ticagrelor as safe alternatives. Closely monitoring blood cell counts is highly suggested in the first month after using clopidogrel. Newer P2Y12 inhibitors, especially ticagrelor, could be effective and safe alternatives if patients had a history of clopidogrel-associated neutropenia.
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PMID:Clopidogrel-Associated Neutropenia: Case Report and Review of the Literature. 2578 70