Low Molecular Weight Heparin Significantly Reduces Embolisation After Carotid Endarterectomy - A Randomised Controlled Trial
ABSTRACT The administration of unfractionated heparin (UFH) prior to carotid clamping during carotid endarterectomy (CEA) transiently increases the platelet aggregation response to arachidonic acid (AA) despite the use of aspirin. We hypothesized that this phenomenon might be reduced by using low molecular weight heparin (LMWH) resulting in fewer emboli in the early post-operative period.
183 aspirinated patients undergoing CEA were randomised to 5000 IU UFH (n=91) or 2500 IU LMWH (dalteparin, n=92) prior to carotid clamping. End-points were: transcranial Doppler (TCD) measurement of embolisation, effect on bleeding and platelet aggregation to AA and adenosine 5'-diphosphate (ADP).
Patients randomised to UFH had twice the odds of experiencing a higher number of emboli in the first 3h after CEA, than those randomised to LMWH (p=0.04). This was not associated with increased bleeding (mean time from flow restoration to operation end: 23 min (UFH) vs. 24 min (LMWH), p=0.18). Platelet aggregation to AA increased significantly following heparinisation, but was unaffected by heparin type (p=0.90). The platelets of patients randomised to LMWH exhibited significantly lower aggregation to ADP compared to UFH (p<0.0001).
Intravenous LMWH is associated with a significant reduction in post-operative embolisation without increased bleeding. The higher rate of embolisation seen with UFH may be mediated by increased platelet aggregation to ADP, rather than to AA.
Full-textDOI: · Available from: Chris I Jones, May 30, 2015
SourceAvailable from: Ross Naylor
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ABSTRACT: 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.Thrombosis and Haemostasis 03/2013; 109(5). DOI:10.1160/TH12-11-0793 · 5.76 Impact Factor
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ABSTRACT: The objective of this review was to identify causes of stroke/death after carotid endarterectomy (CEA) and to develop transferable strategies for preventing stroke/death after CEA, via an overview of a 21-year series of themed research and audit projects. Three preventive strategies were identified: (i) intra-operative transcranial Doppler (TCD) ultrasound and completion angioscopy which virtually abolished intra-operative stroke, primarily through the removal of residual luminal thrombus prior to restoration of flow; (ii) dual antiplatelet therapy with a single 75-mg dose of clopidogrel the night before surgery in addition to regular 75 mg aspirin which virtually abolished post-operative thromboembolic stroke and may also have contributed towards a decline in stroke/death following major cardiac events; and (iii) the provision of written guidance for managing post-CEA hypertension which was associated with virtual abolition of intracranial haemorrhage and stroke as a result of hyperperfusion syndrome. The pathophysiology of peri-operative stroke is multifactorial and no single monitoring or therapeutic strategy will reduce its prevalence. Two of the preventive strategies developed during this 21-year project (peri-operative dual antiplatelet therapy, published guidance for managing post-CEA hypertension) are easily transferable to practices elsewhere.European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 06/2013; 46(2). DOI:10.1016/j.ejvs.2013.05.005 · 3.07 Impact Factor