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.
- SourceAvailable from: Ross Naylor[show abstract] [hide abstract]
ABSTRACT: Postoperative thromboembolic stroke affects 2% to 3% of patients undergoing carotid endarterectomy (CEA) and is preceded by 1 to 2 hours of increasing cerebral embolization. Previous work has demonstrated that high rates of postoperative embolization are associated with increased platelet reactivity to adenosine 5'-diphosphate (ADP). Our hypothesis was that preoperative administration of the platelet ADP antagonist clopidogrel could reduce postoperative embolization. One hundred CEA patients on routine aspirin therapy (150 mg) were randomized to 75 mg clopidogrel (n=46) or placebo (n=54) the night before surgery. Platelet response to ADP was assessed by whole-blood flow cytometry. The number of emboli detected by transcranial Doppler within 3 hours of CEA was independently quantified. Time taken from flow restoration to skin closure was used as an indirect measure of the time to secure hemostasis. In comparison with placebo, clopidogrel produced a small (8.8%) but significant reduction in the platelet response to ADP (P<0.05) while conferring a 10-fold reduction in the relative risk of those patients having >20 emboli in the postoperative period (odds ratio, 10.23; 95% CI, 1.3 to 83.3; P=0.01, Fisher's exact test). However, in the clopidogrel-treated patients, the time from flow restoration to skin closure (an indirect marker of hemostasis) was significantly increased (P=0.04, Fisher's exact test), although there was no increase in bleeding complications or blood transfusions. This is the first study to show that a CEA patient's postoperative thromboembolic potential can be significantly reduced by targeted preoperative antiplatelet therapy without increasing the risk of bleeding complications.Circulation 04/2004; 109(12):1476-81. · 15.20 Impact Factor
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ABSTRACT: Low molecular weight heparin is reported to be less reactive with platelets than larger heparins. We probed the molecular basis for this pattern of reactivity by characterizing the saturable platelet binding of [3H]heparin in plasma using heparins of different molecular weights (Mr approximately 3000, approximately 5000, approximately 10,000, approximately 15,000). Binding affinity increased with increasing molecular weight, as expressed by decreasing apparent dissociation constants (Kdapp approximately 1.3 microM for Mr approximately 3000, to Kdapp approximately 0.31 microM for Mr approximately 15,000). After adjusting for the effect of antithrombin III in the plasma, true dissociation constants (Kd) could be calculated and these showed the same trend with molecular weight (Kd approximately 1.1 microM for Mr approximately 3000 to Kd approximately 0.096 microM for Mr approximately 15,000). Platelet binding capacity for the different heparin fractions also increased with molecular weight, although this correlation appeared to lessen with the largest species. Heparin antithrombin III affinity was shown not to affect heparin binding to platelets. We propose a model in which heparin binding to platelets is mediated by charge interaction. Larger molecules with more charge bind with greater affinity and to sites with a broader range of electronegativity than do smaller, lessBritish Journal of Haematology 04/1990; 74(3):306-12. · 4.94 Impact Factor
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ABSTRACT: The current risk of stroke after carotid endarterectomy may be worse than reported in the international trials. Because studies have suggested that most operative strokes follow surgeon error, the aim of the current study was to audit the impact of introducing a strategy of perioperative monitoring and quality control assessment on outcome. A total of 500 patients underwent carotid endarterectomy with intraoperative transcranial Doppler scan monitoring, completion angioscopy, and 3 hours of postoperative transcranial Doppler scan monitoring. The last of these guided selective dextran therapy in patients with high rates of postoperative embolization, which in previous series has been shown to be highly predictive of progression to thromboembolic stroke. Intimal flaps were repaired in 3% of patients and luminal thrombus removed in 4% of patients. The rate of intraoperative stroke was 0.2%. A total of 313 patients had more than one embolus detected postoperatively (96% within 2 hours of flow restoration), but only 22 patients had sustained embolization requiring dextran. Embolization ceased in all but one patient receiving dextran, although the dose had to be increased in seven patients (36%). One patient was unable to receive adequate dextran therapy because of severe cardiac failure. Overall, the 30-day death/stroke rate was 2.2%, no patient had a perioperative stroke because of carotid thrombosis, and the rate of ipsilateral embolic stroke was 0.8%. Most complications resulted from cardiac pathology or intracranial hemorrhage. A program of monitoring and quality control assessment has been associated with a 60% decrease in the operative risk in comparison with that observed before implementation of the protocol.Journal of Vascular Surgery 11/2000; 32(4):750-9. · 2.88 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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