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Title of Journal: J Thromb Thrombolysis

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Abbravation: Journal of Thrombosis and Thrombolysis

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Springer US

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DOI

10.1002/asna.19051680212

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1573-742X

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Comparative efficacy of in vitro and in vivo metab

Authors: Jawaad Sheriff Gaurav Girdhar WeiChe Chiu Jolyon Jesty Marvin J Slepian Danny Bluestein
Publish Date: 2013/09/17
Volume: 37, Issue: 4, Pages: 499-506
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Abstract

Ventricular assist devices VADs are implanted in patients with endstage heart failure to provide both short and longterm hemodynamic support Unfortunately bleeding and thromboembolic complications due to the severely disturbed dynamic flow conditions generated within these devices require complex longterm antiplatelet and anticoagulant therapy While several studies have examined the effectiveness of one such agent aspirin under flow conditions data comparing the efficacy of in vitro and in vivo metabolized aspirin is lacking Two sets of studies were conducted in vitro with purified human platelets circulating for 30 min in a flow loop containing the DeBakey VAD MicroMed Cardiovascular Houston TX USA a 20 μM aspirin was added exogenously in vitro to platelets isolated from aspirinfree subjects and b platelets were obtained from donors 2 h n = 14 and 20 h n = 13 after ingestion of 1000 mg aspirin Near realtime platelet activation state PAS was measured with a modified prothrombinasebased assay Platelets exposed to aspirin in vitro and in vivo metabolized showed 282 and 253  reduction in platelet activation rate respectively compared to untreated controls Our results demonstrate that in vitro treatment with antiplatelet drugs such as aspirin is as effective as in vivo metabolized aspirin in testing the effect of reducing shearinduced platelet activation in the VAD Using the PAS assay provides a practical in vitro alternative to in vivo testing of antiplatelet efficacy as well as for testing the thrombogenic performance of devices during their research and developmentThe authors thank Dr Sheela George for her assistance with experiments and the Stony Brook University Medical Center Chemistry Lab for salicylate measurements This work was supported by the National Institute of Biomedical Imaging and Bioengineering Quantum Grant Award No 5U01EB01248700 Dr Bluestein

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