Inhibition and reversal of platelet aggregation by αIIbβ3 antagonists depends on the anticoagulant and flow conditions: differential effects of Abciximab and Lamifiban

Summary Shear influences platelet aggregate formation and stability, as well as the inhibitory capacities of antithrombotic drugs. We compared the inhibitory and disaggregating properties of two distinct αIIbβ3 antagonists, Abciximab and Lamifiban, on platelet aggregation induced by adenosine diphos...

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Veröffentlicht in:British journal of haematology 2005-11, Vol.131 (3), p.348-355
Hauptverfasser: Frojmovic, Mony, Labarthe, Benoit, Legrand, Chantal
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creator Frojmovic, Mony
Labarthe, Benoit
Legrand, Chantal
description Summary Shear influences platelet aggregate formation and stability, as well as the inhibitory capacities of antithrombotic drugs. We compared the inhibitory and disaggregating properties of two distinct αIIbβ3 antagonists, Abciximab and Lamifiban, on platelet aggregation induced by adenosine diphosphate (ADP) (5 μmol/l) in platelet‐rich plasma (PRP), in an aggregometer (poorly defined low shear,
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We compared the inhibitory and disaggregating properties of two distinct αIIbβ3 antagonists, Abciximab and Lamifiban, on platelet aggregation induced by adenosine diphosphate (ADP) (5 μmol/l) in platelet‐rich plasma (PRP), in an aggregometer (poorly defined low shear, &lt;100/s) and in a microcouette at arterial shear rate (1000/s). Platelet aggregation was detected by changes in light transmission in the aggregometer (TA), and by particle counting with a flow cytometer (PA). Lamifiban (1 μmol/l) completely inhibited TA or PA induced by ADP in citrated PRP in the aggregometer or microcouette. In contrast, Abciximab (2 μmol/l) only partially inhibited PA in the microcouette while blocking both TA and PA in the aggregometer. Moreover, Abciximab did not reverse platelet aggregates formed either in the microcouette or in the aggregometer, whereas Lamifiban caused complete reversal. On the contrary, Abciximab completely inhibited platelet aggregation induced by ADP in hirudin/d‐Phe–Pro–Arg–chloromethylketone PRP in the microcouette. 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We compared the inhibitory and disaggregating properties of two distinct αIIbβ3 antagonists, Abciximab and Lamifiban, on platelet aggregation induced by adenosine diphosphate (ADP) (5 μmol/l) in platelet‐rich plasma (PRP), in an aggregometer (poorly defined low shear, &lt;100/s) and in a microcouette at arterial shear rate (1000/s). Platelet aggregation was detected by changes in light transmission in the aggregometer (TA), and by particle counting with a flow cytometer (PA). Lamifiban (1 μmol/l) completely inhibited TA or PA induced by ADP in citrated PRP in the aggregometer or microcouette. In contrast, Abciximab (2 μmol/l) only partially inhibited PA in the microcouette while blocking both TA and PA in the aggregometer. Moreover, Abciximab did not reverse platelet aggregates formed either in the microcouette or in the aggregometer, whereas Lamifiban caused complete reversal. On the contrary, Abciximab completely inhibited platelet aggregation induced by ADP in hirudin/d‐Phe–Pro–Arg–chloromethylketone PRP in the microcouette. Our results demonstrate a marked dependence of inhibitory capacity of Abciximab on shear conditions, with citrate anticoagulant responsible for the residual aggregation, in contrast to Lamifiban, another αIIbβ3 antagonist interacting with a distinct site on β3.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><doi>10.1111/j.1365-2141.2005.05782.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects aggregation
Biological and medical sciences
Hematologic and hematopoietic diseases
Medical sciences
platelet
shear
αIIbβ3 antagonists
title Inhibition and reversal of platelet aggregation by αIIbβ3 antagonists depends on the anticoagulant and flow conditions: differential effects of Abciximab and Lamifiban
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