Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey ventricular assist device

Jawaad Sheriff, Gaurav Girdhar, Wei Che Chiu, Jolyon Jesty, Marvin J Slepian, Danny Bluestein

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Ventricular assist devices (VADs) are implanted in patients with end-stage heart failure to provide both short- and long-term hemodynamic support. Unfortunately, bleeding and thromboembolic complications due to the severely disturbed, dynamic flow conditions generated within these devices require complex, long-term 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 aspirin-free subjects, and (b) platelets were obtained from donors 2 h (n = 14) and 20 h (n = 13) after ingestion of 1,000 mg aspirin. Near real-time platelet activation state (PAS) was measured with a modified prothrombinase-based assay. Platelets exposed to aspirin in vitro and in vivo (metabolized) showed 28.2 and 25.3 % 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 shear-induced 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 development.

Original languageEnglish (US)
Pages (from-to)499-506
Number of pages8
JournalJournal of Thrombosis and Thrombolysis
Volume37
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Heart-Assist Devices
Aspirin
Platelet Activation
Blood Platelets
Equipment and Supplies
In Vitro Techniques
Platelet Aggregation Inhibitors
Thromboplastin
Anticoagulants
Heart Failure
Eating
Hemodynamics
Tissue Donors
Hemorrhage
Therapeutics
Research

Keywords

  • Aspirin
  • Platelets
  • Thrombin
  • Ventricular assist devices

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey ventricular assist device. / Sheriff, Jawaad; Girdhar, Gaurav; Chiu, Wei Che; Jesty, Jolyon; Slepian, Marvin J; Bluestein, Danny.

In: Journal of Thrombosis and Thrombolysis, Vol. 37, No. 4, 2014, p. 499-506.

Research output: Contribution to journalArticle

Sheriff, Jawaad ; Girdhar, Gaurav ; Chiu, Wei Che ; Jesty, Jolyon ; Slepian, Marvin J ; Bluestein, Danny. / Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey ventricular assist device. In: Journal of Thrombosis and Thrombolysis. 2014 ; Vol. 37, No. 4. pp. 499-506.
@article{5effc44801bb436b90d314126c64194f,
title = "Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey ventricular assist device",
abstract = "Ventricular assist devices (VADs) are implanted in patients with end-stage heart failure to provide both short- and long-term hemodynamic support. Unfortunately, bleeding and thromboembolic complications due to the severely disturbed, dynamic flow conditions generated within these devices require complex, long-term 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 aspirin-free subjects, and (b) platelets were obtained from donors 2 h (n = 14) and 20 h (n = 13) after ingestion of 1,000 mg aspirin. Near real-time platelet activation state (PAS) was measured with a modified prothrombinase-based assay. Platelets exposed to aspirin in vitro and in vivo (metabolized) showed 28.2 and 25.3 {\%} 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 shear-induced 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 development.",
keywords = "Aspirin, Platelets, Thrombin, Ventricular assist devices",
author = "Jawaad Sheriff and Gaurav Girdhar and Chiu, {Wei Che} and Jolyon Jesty and Slepian, {Marvin J} and Danny Bluestein",
year = "2014",
doi = "10.1007/s11239-013-0997-6",
language = "English (US)",
volume = "37",
pages = "499--506",
journal = "Journal of Thrombosis and Thrombolysis",
issn = "0929-5305",
publisher = "Springer Netherlands",
number = "4",

}

TY - JOUR

T1 - Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey ventricular assist device

AU - Sheriff, Jawaad

AU - Girdhar, Gaurav

AU - Chiu, Wei Che

AU - Jesty, Jolyon

AU - Slepian, Marvin J

AU - Bluestein, Danny

PY - 2014

Y1 - 2014

N2 - Ventricular assist devices (VADs) are implanted in patients with end-stage heart failure to provide both short- and long-term hemodynamic support. Unfortunately, bleeding and thromboembolic complications due to the severely disturbed, dynamic flow conditions generated within these devices require complex, long-term 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 aspirin-free subjects, and (b) platelets were obtained from donors 2 h (n = 14) and 20 h (n = 13) after ingestion of 1,000 mg aspirin. Near real-time platelet activation state (PAS) was measured with a modified prothrombinase-based assay. Platelets exposed to aspirin in vitro and in vivo (metabolized) showed 28.2 and 25.3 % 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 shear-induced 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 development.

AB - Ventricular assist devices (VADs) are implanted in patients with end-stage heart failure to provide both short- and long-term hemodynamic support. Unfortunately, bleeding and thromboembolic complications due to the severely disturbed, dynamic flow conditions generated within these devices require complex, long-term 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 aspirin-free subjects, and (b) platelets were obtained from donors 2 h (n = 14) and 20 h (n = 13) after ingestion of 1,000 mg aspirin. Near real-time platelet activation state (PAS) was measured with a modified prothrombinase-based assay. Platelets exposed to aspirin in vitro and in vivo (metabolized) showed 28.2 and 25.3 % 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 shear-induced 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 development.

KW - Aspirin

KW - Platelets

KW - Thrombin

KW - Ventricular assist devices

UR - http://www.scopus.com/inward/record.url?scp=84899965406&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899965406&partnerID=8YFLogxK

U2 - 10.1007/s11239-013-0997-6

DO - 10.1007/s11239-013-0997-6

M3 - Article

C2 - 24043375

AN - SCOPUS:84899965406

VL - 37

SP - 499

EP - 506

JO - Journal of Thrombosis and Thrombolysis

JF - Journal of Thrombosis and Thrombolysis

SN - 0929-5305

IS - 4

ER -