Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option : use of 96-well Optimul assay

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Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option : use of 96-well Optimul assay. / Lordkipanidze, M.; Lowe, G. C.; Kirkby, N. S.; Chan, M. V.; Lundberg, M. H.; Morgan, N. V.; Bem, D.; Nisar, S. P.; Leo, V. C.; Jones, M. L.; Mundell, S. J.; Daly, M. E.; Mumford, A. D.; Warner, T. D.; Watson, S. P.

In: Blood, Vol. 123, No. 8, 20.02.2014, p. e11-e22.

Research output: Contribution to journalArticlepeer-review

Harvard

Lordkipanidze, M, Lowe, GC, Kirkby, NS, Chan, MV, Lundberg, MH, Morgan, NV, Bem, D, Nisar, SP, Leo, VC, Jones, ML, Mundell, SJ, Daly, ME, Mumford, AD, Warner, TD & Watson, SP 2014, 'Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option : use of 96-well Optimul assay', Blood, vol. 123, no. 8, pp. e11-e22. https://doi.org/10.1182/blood-2013-08-520387

APA

Lordkipanidze, M., Lowe, G. C., Kirkby, N. S., Chan, M. V., Lundberg, M. H., Morgan, N. V., Bem, D., Nisar, S. P., Leo, V. C., Jones, M. L., Mundell, S. J., Daly, M. E., Mumford, A. D., Warner, T. D., & Watson, S. P. (2014). Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option : use of 96-well Optimul assay. Blood, 123(8), e11-e22. https://doi.org/10.1182/blood-2013-08-520387

Vancouver

Author

Lordkipanidze, M. ; Lowe, G. C. ; Kirkby, N. S. ; Chan, M. V. ; Lundberg, M. H. ; Morgan, N. V. ; Bem, D. ; Nisar, S. P. ; Leo, V. C. ; Jones, M. L. ; Mundell, S. J. ; Daly, M. E. ; Mumford, A. D. ; Warner, T. D. ; Watson, S. P. / Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option : use of 96-well Optimul assay. In: Blood. 2014 ; Vol. 123, No. 8. pp. e11-e22.

Bibtex

@article{9e49798601ce427a80eb94d81ca97772,
title = "Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option : use of 96-well Optimul assay",
abstract = "Up to 1% of the population have mild bleeding disorders, but these remain poorly characterized, particularly with regard to the roles of platelets. We have compared the usefulness of Optimul, a 96-well plate-based assay of 7 distinct pathways of platelet activation to characterize inherited platelet defects in comparison with light transmission aggregometry (LTA). Using Optimul and LTA, concentration-response curves were generated for arachidonic acid, ADP, collagen, epinephrine, Thrombin receptor activating-peptide, U46619, and ristocetin in samples from (1) healthy volunteers (n = 50), (2) healthy volunteers treated with antiplatelet agents in vitro (n = 10), and (3) patients with bleeding of unknown origin (n = 65). The assays gave concordant results in 82% of cases (κ = 0.62, P < .0001). Normal platelet function results were particularly predictive (sensitivity, 94%; negative predictive value, 91%), whereas a positive result was not always substantiated by LTA (specificity, 67%; positive predictive value, 77%). The Optimul assay was significantly more sensitive at characterizing defects in the thromboxane pathway, which presented with normal responses with LTA. The Optimul assay is sensitive to mild platelet defects, could be used as a rapid screening assay in patients presenting with bleeding symptoms, and detects changes in platelet function more readily than LTA. This trial was registered at www.isrctn.org as #ISRCTN 77951167.",
author = "M. Lordkipanidze and Lowe, {G. C.} and Kirkby, {N. S.} and Chan, {M. V.} and Lundberg, {M. H.} and Morgan, {N. V.} and D. Bem and Nisar, {S. P.} and Leo, {V. C.} and Jones, {M. L.} and Mundell, {S. J.} and Daly, {M. E.} and Mumford, {A. D.} and Warner, {T. D.} and Watson, {S. P.}",
year = "2014",
month = feb,
day = "20",
doi = "10.1182/blood-2013-08-520387",
language = "English",
volume = "123",
pages = "e11--e22",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "8",

}

RIS

TY - JOUR

T1 - Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option : use of 96-well Optimul assay

AU - Lordkipanidze, M.

AU - Lowe, G. C.

AU - Kirkby, N. S.

AU - Chan, M. V.

AU - Lundberg, M. H.

AU - Morgan, N. V.

AU - Bem, D.

AU - Nisar, S. P.

AU - Leo, V. C.

AU - Jones, M. L.

AU - Mundell, S. J.

AU - Daly, M. E.

AU - Mumford, A. D.

AU - Warner, T. D.

AU - Watson, S. P.

PY - 2014/2/20

Y1 - 2014/2/20

N2 - Up to 1% of the population have mild bleeding disorders, but these remain poorly characterized, particularly with regard to the roles of platelets. We have compared the usefulness of Optimul, a 96-well plate-based assay of 7 distinct pathways of platelet activation to characterize inherited platelet defects in comparison with light transmission aggregometry (LTA). Using Optimul and LTA, concentration-response curves were generated for arachidonic acid, ADP, collagen, epinephrine, Thrombin receptor activating-peptide, U46619, and ristocetin in samples from (1) healthy volunteers (n = 50), (2) healthy volunteers treated with antiplatelet agents in vitro (n = 10), and (3) patients with bleeding of unknown origin (n = 65). The assays gave concordant results in 82% of cases (κ = 0.62, P < .0001). Normal platelet function results were particularly predictive (sensitivity, 94%; negative predictive value, 91%), whereas a positive result was not always substantiated by LTA (specificity, 67%; positive predictive value, 77%). The Optimul assay was significantly more sensitive at characterizing defects in the thromboxane pathway, which presented with normal responses with LTA. The Optimul assay is sensitive to mild platelet defects, could be used as a rapid screening assay in patients presenting with bleeding symptoms, and detects changes in platelet function more readily than LTA. This trial was registered at www.isrctn.org as #ISRCTN 77951167.

AB - Up to 1% of the population have mild bleeding disorders, but these remain poorly characterized, particularly with regard to the roles of platelets. We have compared the usefulness of Optimul, a 96-well plate-based assay of 7 distinct pathways of platelet activation to characterize inherited platelet defects in comparison with light transmission aggregometry (LTA). Using Optimul and LTA, concentration-response curves were generated for arachidonic acid, ADP, collagen, epinephrine, Thrombin receptor activating-peptide, U46619, and ristocetin in samples from (1) healthy volunteers (n = 50), (2) healthy volunteers treated with antiplatelet agents in vitro (n = 10), and (3) patients with bleeding of unknown origin (n = 65). The assays gave concordant results in 82% of cases (κ = 0.62, P < .0001). Normal platelet function results were particularly predictive (sensitivity, 94%; negative predictive value, 91%), whereas a positive result was not always substantiated by LTA (specificity, 67%; positive predictive value, 77%). The Optimul assay was significantly more sensitive at characterizing defects in the thromboxane pathway, which presented with normal responses with LTA. The Optimul assay is sensitive to mild platelet defects, could be used as a rapid screening assay in patients presenting with bleeding symptoms, and detects changes in platelet function more readily than LTA. This trial was registered at www.isrctn.org as #ISRCTN 77951167.

U2 - 10.1182/blood-2013-08-520387

DO - 10.1182/blood-2013-08-520387

M3 - Article

C2 - 24408324

VL - 123

SP - e11-e22

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -