Evidence map›Paper›PMID 20473398›Full record

ArticleIntegrative biology : quantitative biosciences from nano to macro2010

P2Y12 or P2Y1 inhibitors reduce platelet deposition in a microfluidic model of thrombosis while apyrase lacks efficacy under flow conditions.

S F Maloney, Lawrence F Brass, S L Diamond

Open access · greenAbstract read
In one paragraph

Article in Integrative biology : quantitative biosciences from nano to macro, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed, 98 citations in OpenAlex.

  1. Trial
  2. Design and Pharmacological Characterization of a Novel Antithrombotic P2YInternational journal of molecular sciences · 2025
    Article
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  4. Article
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  7. "Going with the flow" in modeling fibrinolysis.Frontiers in cardiovascular medicine · 2022
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Microfluidic hemophilia models using blood from healthy donors.Research and practice in thrombosis and haemostasis · 2020
    Article
  15. Article
  16. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

S F MaloneyDepartment of Chemical and Biomolecular Engineering, Division of Hematology and Oncology, Institute for Medicine and Engineering, 1024 Vagelos Research Laboratories, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lawrence F Brass
S L Diamond
University of Pennsylvania · US

Funding

Subcellular Mechanisms pf Platelet ActivationP01HL040387 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI PONCZ, MORTIMER · 1988 to 2018
$35.5M
TRAINING GRANT IN HEMOSTASIS AND THROMBOSIST32HL007971 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Rodney M Camire · 2001 to 2026
$10.6M
Reaction and Transport Dynamics in Human BloodR01HL056621 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DIAMOND, SCOTT L · 1996 to 2009
$1.8M
Blood Systems BiologyR33HL087317 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DIAMOND, SCOTT L · 2006 to 2008
$937k
Blood systems biologyR33HL087385 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BRASS, LAWRENCE F · 2006 to 2008
$926k
NHLBI NIH HHS HL40387NHLBI NIH HHS HL56621NHLBI NIH HHS P01 HL040387NHLBI NIH HHS R01 HL056621NHLBI NIH HHS R33 HL087317NHLBI NIH HHS R33HL087317NHLBI NIH HHS R33 HL087385NHLBI NIH HHS T32 HL007971NHLBI NIH HHS T32HL007971
6 · The paper itself

Abstract

Determination of the patient-specific response to antiplatelet agents facilitates proper dosing for both acute and chronic prophylaxis. "Closed" systems (with or without flow) may fail to predict pharmacological potency in situations where platelets rapidly accumulate under flow conditions at a site of thrombosis ("Open" systems). Using an 8-channel microfluidic flow assay of human whole blood with corn trypsin inhibitor (+/- PPACK) perfused over focal zones of collagen, dose-response curves were measured for pharmacological agents at a wall shear rate of 210 s(-1). The P2Y(1) inhibitor MRS 2179 (IC(50) = 0.233 +/- 0.132 microM) and P2Y(12) inhibitor 2-MeSAMP (IC(50) = 2.558 +/- 0.799 microM) were potent blockers of secondary platelet accumulation under flow, while the P2X(1) inhibitor (NF 449) and apyrase failed to reduce platelet accumulation. MRS 2179 and 2-MeSAMP had undetectable effects on initial platelet adhesion to collagen. Numerical simulation of convective-diffusive transport and apyrase-mediated catalytic degradation of ADP indicated that ultra-high concentrations of apyrase ( approximately 2000 U mL(-1)) would be required to have the same effect under flow as much lower concentrations (1 U mL(-1)) currently used in closed systems (aggregometry or cone-and-plate viscometer). This is the first evaluation of IC(50) values for P2Y(12) and P2Y(1) antagonists under controlled flow conditions. Evaluation of antiplatelet agents in open flow systems demonstrates that inhibition of either ADP by apyrase or antagonism of P2X(1) signaling had no inhibitory effect on platelet accumulation. This technique provides a platform for rapidly investigating effects of antithrombotic therapies simultaneously in a model injury system.

Indexed as

Purinergic P2 Receptor AntagonistsAmino Acid Chloromethyl KetonesApyraseCells, CulturedHumansMicrofluidic Analytical TechniquesPlatelet AdhesivenessReceptors, Purinergic P2Y1Receptors, Purinergic P2Y12ThrombosisAmino Acid Chloromethyl KetonesApyraseP2RY12 protein, humanP2RY1 protein, humanphenylalanyl-prolyl-arginine-chloromethyl ketonePurinergic P2 Receptor AntagonistsReceptors, Purinergic P2Y1Receptors, Purinergic P2Y12

Identifiers

PMID20473398
PMCPMC4441395
OpenAlexW1980877776

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.