Platelet Glycoprotein IIb/IIIa Inhibitors

Nurden, Alan T.; Poujol, Christel; Durrieu-Jaïs, C; Nurden, Paquita

doi:10.1161/01.atv.19.12.2835

Cited by 55 publications

(42 citation statements)

References 50 publications

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“…[1][2][3][4][5] Currently, the chimeric human mouse monoclonal antibody fragment abciximab (ReoPro, Centocor, Inc), the cyclic heptapeptide eptifibatide (Integrilin, COR Therapeutics, Inc), and the nonpeptide tyrosine derivative tirofiban (Aggrastat, Merck & Co) are GP IIb/IIIa antagonists approved for such use. Because differences between these drugs exist in chemical structure, pharmacokinetics, 6 and the parameters underlying dose-finding studies, current clinical regimens may not have identical pharmacodynamic profiles. For example, tirofiban has been dosed to achieve Ͼ90% inhibition of platelet aggregation (PA) in response to 5 mol/L adenosine diphosphate (ADP) in citrate anticoagulated blood.…”

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confidence: 99%

Randomized COMparison of Platelet Inhibition With Abciximab, TiRofiban and Eptifibatide During Percutaneous Coronary Intervention in Acute Coronary Syndromes

et al. 2002

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Background-Theand eptifibatide regimens (Pϭ0.0001). The abciximab regimen, however, showed increasingly varied anti-aggregatory effects during continued infusion for Ն4 hours. Citrate exaggerated ex vivo platelet inhibition after eptifibatide and tirofiban, but had the opposite effect on abciximab. Of all regimens evaluated, the eptifibatide regimen inhibited PA most consistently throughout both the early and late periods. Conclusions-Currently recommended drug regimens to inhibit the platelet glycoprotein IIb/IIIa receptor have distinct pharmacodynamic profiles that might affect their relative efficacy in acute coronary syndromes and percutaneous coronary intervention.

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confidence: 99%

Randomized COMparison of Platelet Inhibition With Abciximab, TiRofiban and Eptifibatide During Percutaneous Coronary Intervention in Acute Coronary Syndromes

et al. 2002

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“…It has been shown that this GPIIb/IIIa inhibitor, which stops the final common pathway of platelet aggregation, reduces the risk of periprocedural ischemic events associated with pPCI. Abciximab acts rapidly, and the maximum receptor blockade (with subsequent inhibition of platelet aggregation and prolongation of the bleeding time) occurs 2 h after a bolus injection [10,11]. In contrast to other GPIIb/IIIa inhibitors, abciximab has a long half-life and binds additionally to the vitronectin receptor and to whitecell a M b 2 integrin receptors [37].…”

Section: Discussionmentioning

confidence: 99%

“…It is known that 12 h after discontinuation of treatment approximately 75% of receptors remain occupied, and some pharmacological effects of abciximab persist for more than 24 h after drug discontinuation. Small amounts of abciximab may still be detected on circulating platelets 8-15 days later as the antibody redistributes on newly produced platelets [10,11].…”

Section: Discussionmentioning

confidence: 99%

“…Now, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors and thienopyridines, together with aspirin, are a cornerstone of adjunctive medication [5][6][7]. Abciximab, a chimeric antibody fragment, is the most widely used GPIIb/IIIa inhibitor and is distinguished by a long antiplatelet effect [8][9][10][11]. Flow cytometry studies have detected abciximab on circulating platelets up to 2 weeks after discontinuation of treatment [12].…”

Section: Introductionmentioning

confidence: 99%

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Abciximab and left ventricular thrombus formation in early period of acute myocardial infarction treated with successful primary stenting

Zielińska

Kaczmarek

2008

J Thromb Thrombolysis

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“…It mediates platelet aggregation by binding multivalent adhesive proteins, which then form bridges linking adjacent platelets (1). Anti-␣ IIb ␤ 3 serum Abs have been detected in a majority of patients with either the chronic or acute forms of autoimmune thrombocytopenic purpura (AITP) 5 and in patients with Glanzmann thrombasthenia (GT), the inherited disorder of ␣ IIb ␤ 3 , after receiving blood transfusions to stop bleeding (2)(3)(4).…”

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confidence: 99%

Human IgG Monoclonal Anti-αIIbβ3-Binding Fragments Derived from Immunized Donors Using Phage Display

Jacobin

Laroche‐Traineau

Little

et al. 2002

The Journal of Immunology

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Previous studies of the immune response in polytransfused Glanzmann thrombasthenia (GT) patients and in autoimmune thrombocytopenic purpura (AITP) have relied on serum analysis and have shown the frequent development of Abs directed against the αIIbβ3 integrin. However, little is known about the molecular diversity of the humoral immune response to αIIbβ3 due to the paucity of mAbs issuing from these pathologies. We have isolated human IgG anti-αIIbβ3 binding fragments using combinatorial libraries of single-chain IgG created from the B cells of a GT and an AITP patient, both with serum Abs. Ab screening was performed using activated platelets or activated αIIbβ3-expressing Chinese hamster ovary cells. Sequencing of selected phage Abs showed that a broad selection of genes from virtually all V gene families had been used, indicating the diversity of the immune response. About one-half of the VH and VL segments of our IgG anti-αIIbβ3 fragments displayed extensive hypermutations in the complementarity-determining region, supporting the idea that an Ag-driven immune response was occurring in both patients. The H chain complementarity-determining region 3 analysis of phage Abs revealed motifs other than the well-known RGD and KQAGDV integrin-binding sequences. To our knowledge, our study is the first to illustrate multiple human IgG anti-αIIbβ3 reactivities and structural variations linked to the anti-platelet human immune response. Human αIIbβ3 Abs preferentially directed against the activated form of the integrin were further characterized because platelet αIIbβ3 inhibitors are potential therapeutic reagents for treating acute coronary syndromes. Currently available αIIbβ3 antagonists do not specifically recognize the activated form of the integrin.

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Platelet Glycoprotein IIb/IIIa Inhibitors

Cited by 55 publications

References 50 publications

Randomized COMparison of Platelet Inhibition With Abciximab, TiRofiban and Eptifibatide During Percutaneous Coronary Intervention in Acute Coronary Syndromes

Randomized COMparison of Platelet Inhibition With Abciximab, TiRofiban and Eptifibatide During Percutaneous Coronary Intervention in Acute Coronary Syndromes

Abciximab and left ventricular thrombus formation in early period of acute myocardial infarction treated with successful primary stenting

Human IgG Monoclonal Anti-αIIbβ3-Binding Fragments Derived from Immunized Donors Using Phage Display

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