Accessibility navigation


Transient heparin-induced platelet activation linked to generation of platelet 12-lipoxygenase: findings from a randomised controlled trial

McMahon, G. S., Jones, C. I., Hayes, P. D., Naylor, A. R. and Goodall, A. H. (2013) Transient heparin-induced platelet activation linked to generation of platelet 12-lipoxygenase: findings from a randomised controlled trial. Thrombosis and haemostasis, 109 (6). pp. 977-1185. ISSN 0340-6245

Full text not archived in this repository.

It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

To link to this item DOI: 10.1160/TH12-11-0793

Abstract/Summary

Previously we demonstrated that heparin administration during carotid endarterectomy (CEA) caused a marked, but transient increase in platelet aggregation to arachidonic acid (AA) and adenosine diphosphate (ADP), despite effective platelet cyclo-oxygenase-1 (COX-1) inhibition with aspirin. Here we investigated the metabolism of AA via platelet 12-lipoxygenase (12-LOX) as a possible mediator of the observed transient aspirin resistance, and compared the effects of unfractionated (UFH) and low-molecular-weight (LMWH) heparin. A total of 43 aspirinated patients undergoing CEA were randomised in the trial to 5,000 IU UFH (n=22) or 2,500 IU LMWH (dalteparin, n=21). Platelet aggregation to AA (4x10⁻³) and ADP (3x10⁻⁶) was determined, and the products of the COX-1 and 12-LOX pathways; thromboxane B₂ (TXB₂) and 12-hydroxyeicosatretraenoic acid (12-HETE) were measured in plasma, and in material released from aggregating platelets.Aggregation to AA increased significantly (~10-fold) following heparinisation (p<0.0001), irrespective of heparin type (p=0.33). Significant, but smaller (~2-fold) increases in aggregation to ADP were also seen, which were significantly lower in the platelets of patients randomised to LMWH (p<0.0001). Plasma levels of TxB2 did not rise following heparinisation (p=0.93), but 12-HETE increased significantly in the patients' plasma, and released from platelets stimulated in vitro withADP, with both heparin types (p<0.0001). The magnitude of aggregation to ADP correlated with 12-HETE generation (p=0.03). Heparin administration during CEA generates AA that is metabolised to 12-HETE via the 12-LOX pathway, possibly explaining the phenomenon of transient heparin-induced platelet activation. LMWH has less effect on aggregation and 12-HETE generation than UFH when the platelets are stimulated with ADP.

Item Type:Article
Refereed:Yes
Divisions:No Reading authors. Back catalogue items
Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:33132
Uncontrolled Keywords:platelets, heparin, LMWH, RCT, lipoxygenase
Publisher:Cambridge University Press

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation