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.
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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). · 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; · 2.92 Impact Factor
Selected Abstracts from the June Issue of the
European Journal of Vascular and Endovascular Surgery
Piergiorgio Cao, MD, FRCS, Editor-in-Chief, and Jean-Baptiste Ricco, MD, PhD, Senior Editor
Low Molecular Weight Heparin Significantly Reduces Embolisation
After Carotid Endarterectomy – A Randomised Controlled Trial
McMahon G.S., Webster S.E., Hayes P.D., Jones C.I., Goodall A.H.,
Naylor A.R. Eur J Vasc Endovasc Surg 2009;xx:xx-xx.
Objectives: The administration of unfractionated heparin (UFH) prior
to carotid clamping during carotid endarterectomy (CEA) transiently in-
creases 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.
Methods: 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) mea-
surement of embolisation, effect on bleeding and platelet aggregation to AA
and adenosine 5=-diphosphate (ADP).
Results: Patients randomised to UFH had twice the odds of experi-
encing a higher number of emboli in the first 3 h 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).
Conclusions: 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.
Thoracoabdominal Aortic Aneurysm Repair: Results of Conventional
Schepens M.A., Heijmen R.H., Ranschaert W., Sonker U., Morshuis W.J.
Eur J Vasc Endovasc Surg 2009;xx:xx-xx.
Objectives: The aim of this study is to report our experience in the
surgical repair of thoracoabdominal aortic aneurysms (TAAAs) over the last
27 years against the background of evolving surgical techniques.
Methods: We reviewed the prospectively collected data of 571 patients
who underwent open TAAA repair between 1981 and 2008. Data were
analysed using univariate and multivariate analysis (logistic regression). Pre-,
intra- and postoperative risk factors were used to develop risk models for
in-hospital mortality, spinal cord deficit and renal failure. Recent published
series were used to highlight the different treatment modalities and explore
Results: Seventy patients (12.3%) died in the hospital, the 30-day
patients (8.3%) developed paraplegia or paraparesis. The incidence of para-
plegia in the left heart bypass group was 4.4%. The predictors for hospital
mortality were increasing age (odds ratio 1.096 per year, 95% confidence
CI: 4.7–21.1). For postoperative spinal cord deficit, we found three protect-
ing factors: age above 75 years (odds ratio 0.14, 95% CI: 0.19–1.09), the
presence of a post-dissection aneurysm (odds ratio 0.4, 95% CI: 0.17–0.94)
and the combined use of cerebrospinal fluid drainage and motor-evoked
potentials (odds ratio 0.28, 95% CI: 0.14–0.56). The urgency of procedure
(odds ratio 4, 95% CI: 1.8–9) and preoperative serum creatinine level (odds
ratio 1.007 per micromole per litre, 95% CI: 1.0–1.01) were significant risk
factors for renal failure.
Conclusions: Open TAAA repair intrinsically has substantial compli-
cations, of which spinal cord ischaemia and renal failure are the most
devastating, despite major progress in our understanding of the pathophys-
iology and operative strategy. An overview of the results of recently pub-
lished series is given along with an analysis of our data.
Atherosclerosis and Disc Degeneration/Low-Back Pain – A Systematic
Kauppila L.I. Eur J Vasc Endovasc Surg 2009;xx:xx-xx.
Objectives: Atherosclerosis can obstruct branching arteries of the
abdominal aorta, including four paired lumbar arteries and the middle sacral
artery that feed the lumbar spine. The diminished blood flow could result in
various back problems. The aim of this systematic literature review was to
assess associations between atherosclerosis and disc degeneration (DD) or
low-back pain (LBP).
Data sources: A systematic search of the Medline/PubMed database
for all original articles on atherosclerosis and DD/LBP published until
October 2008. The search was performed with the medical subject
headings atherosclerosis, cardiovascular risk factor, or vascular disease
and keywords “disc degeneration”, “disc herniation”, and “back pain”
on the basis of MeSH tree and as a text search. In addition reference lists
were studied and searched manually. Observational studies investigating
the association of atherosclerosis or its risk factors and lumbar DD/LBP
Review methods: The following data were extracted: study character-
istics, duration of follow-up, year of publication, findings of atherosclerosis/
cardiovascular risk factors and DD/LBP. Disc herniation was regarded as a
form of disc degeneration and cardiovascular risk factors were regarded as
surrogate for atherosclerosis in epidemiological studies.
Results: One hundred and seventy-nine papers were identified. After
exclusion of case reports, letters, editorials, papers not related to the lumbar
spine, and animal studies, 25 papers were included. Post-mortem studies
well as between occluded lumbar arteries and life-time LBP. In clinical
studies, aortic calcification was associated with LBP, and stenosis of lumbar
arteries was associated with both DD and LBP. In epidemiological studies,
smoking and high serum cholesterol levels were found to have the most
consistent associations with DD and LBP.
Conclusion: Aortic atherosclerosis and stenosis of the feeding arteries of
the lumbar spine were associated with DD and LBP. Cardiovascular risk factors
clarify the association of atherosclerosis and low-back disorders.
A Study of Pullout Forces of the Components of Modular Multi-
manufacturer Hybrid Endografts Used for Aortic Aneurysm Repair
Cinà D.P., Grant G., Peterson M., Campbell V., Garrido-Olivares L., Cinà
C.S. Eur J Vasc Endovasc Surg 2009;xx:xx-xx.
Objectives: Aorto-iliac angulations may be challenging for modular
stent-graft systems (SGSs) from a single manufacturer. This study aims to
define the pullout forces (POFs) of SGSs derived from the same (non-
hybrid) or different manufacturers (hybrid).
Methods: The POFs were tested in a vertical position in air and 5%
albumin. We studied the POFs between legs from Anaconda (Vascutek®),
Excluder (Gore®), Talent (Medtronic®) and Zenith (Cook®) with the
contralateral limb of bifurcated aortic bodies from Zenith (12 mm), Ana-
conda and Excluder.
Results: For non-hybrid SGSs, the POFs decreased in the following
order: Anaconda (11.2 ? 0.6 N), Talent (6.25? 0.6 N), Zenith (3.5 ? 0.01 N)
and Excluder (2.5 ? 0.5 N). The Zenith body with the Anaconda limb
(15 mm) registered the greatest POF (13.083 ? 0.821 N); the Zenith and
Excluder bodies combined with the Excluder limb (16 mm) registered the
weakest POFs (2.397 ? 0.22 N and 2.500 ? 0.479 N, respectively). The Ze-
nith body combined with the Excluder limb (16 mm) had a POF similar to the
Zenith non-hybrid; combined with Talent 14 mm and Anaconda limb exhib-
ited POFs greater than the Zenith non-hybrid system. For the limb-to-limb
POFs, the greatest was registered for the Anaconda limb, 13 mm within a
12-mm extension for 40-mm overlaps (23.06 ? 0.480 N); the weakest POFs
were recorded for the Excluder limbs at 30-mm overlaps (1.09 ? 0.167 N and
1.11 ? 0.250 N).
Conclusions: The hybrid SGSs performed as well as or better than the
non-hybrid systems, and should be considered for clinical testing in patients
whose unique anatomy warrants the flexibility that the use of hybrids
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