Lyophilised reconstituted human platelets increase thrombus formation in a clinical ex vivo model of deep arterial injury

Nikhil Vilas Joshi; Jennifer B. Raftis; Andrew J. Lucking; Amanda H. Hunter; Mike Millar; Mike Fitzpatrick; Giora Z. Feuerstein; David E. Newby

doi:10.1160/TH12-02-0059

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2012; 108(01): 176-182
DOI: 10.1160/TH12-02-0059

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Lyophilised reconstituted human platelets increase thrombus formation in a clinical ex vivo model of deep arterial injury

Nikhil Vilas Joshi

¹Centre for Cardiovascular Sciences, University of Edinburgh, UK

,

Jennifer B. Raftis

²Centre for Inflammation Research, University of Edinburgh, UK

,

Andrew J. Lucking

¹Centre for Cardiovascular Sciences, University of Edinburgh, UK

,

Amanda H. Hunter

¹Centre for Cardiovascular Sciences, University of Edinburgh, UK

,

Mike Millar

³Centre for Reproductive Health, University of Edinburgh, UK

,

Mike Fitzpatrick

⁴Cellphire INC., Rockville, Maryland, USA

,

Giora Z. Feuerstein

⁴Cellphire INC., Rockville, Maryland, USA

,

David E. Newby

¹Centre for Cardiovascular Sciences, University of Edinburgh, UK

› Author Affiliations

Abstract

Summary

Platelets are the principal component of the innate haemostatic system that protect from traumatic bleeding. We investigated whether lyophilised human platelets (LHPs) could enhance clot formation within platelet-free and whole blood environments using an ex vivo model of deep arterial injury. Lyophilised human platelets were produced from stored human platelets and characterised using conventional, fluorescent and electron microscopic techniques. LHPs were resuspended in platelet-free plasma (PFP) obtained from citrated whole human blood to form final concentrations of 0,20 and 200 × 10⁹ LHPs/L. LHPs with recalcified PFP or whole blood were perfused through the chamber at low (212 s^-1) and high (1,690 s^-1) shear rates with porcine aortic tunica media as thrombogenic substrate. LHPs shared morphological characteristics with native human platelets and were incorporated into clot generated from PFP or whole blood. Histomorphometrically measured mean thrombus area increased in a dose-dependent manner following the addition of LHPs to PFP under conditions of high shear [704 μm² ± 186 μm² (mean ± SEM), 1,511 μm² ± 320 μm² and 2,378 μm² ± 315 μm², for LHPs at 0, 20 and 200 × 10⁹ /l, respectively (p= 0.012)]. Lyophil-ised human platelets retain haemostatic properties when reconstituted in both PFP and whole blood, and enhance thrombus formation in a model of deep arterial injury. These data suggest that LHPs have the potential to serve as a therapeutic intervention during haemorrhage under circumstances of trauma, and platelet depletion or dysfunction.

Keywords

Bleeding disorders - haemostasis - lyophilised human platelets - platelet substitutes

Full Text

References

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