Jonathan Smout

Current practice in the use of antiplatelet agents in the peri-operative period by UK vascular surgeons.

BACKGROUND There currently appears to be no firm consensus with regards to the use of antiplatelet agents during the peri-operative period in vascular surgical practice. METHODS A nine-part questionnaire relating to peri-operative antiplatelet use was sent to 137 ordinary members of the Vascular Surgical Society of Great Britain and Ireland (VSS-GBI). RESULTS Of the 137 questionnaires sent, 90 were returned (66%). For patients undergoing infra-inguinal bypass, carotid endarterectomy and varicose vein surgery, over 90% of vascular surgeons continue antiplatelet agents peri-operatively; however, in the case of aortic aneurysm repair, this figure is lower (77%). Three of the respondents stated that they would stop clopidogrel, but not aspirin, prior to surgery because of concerns over increased operative bleeding. In patients starting routine heparin prophylaxis against thrombosis, most surgeons opted to continue antiplatelet therapy (82%), although in patients requiring therapeutic heparin treatment, opinions were almost equally split. Most vascular surgeons (93%) would to start an alternative antiplatelet agent if a patient was intolerant of aspirin for gastrointestinal reasons. CONCLUSIONS Although the benefits of antiplatelet drugs in the long-term reduction of vascular events is established, evidence supporting their use in the peri-operative period is scarce. The general consensus of opinion from this survey suggests that most vascular surgeons do not stop antiplatelet drugs pre-operatively.

Carotid artery stenting: relationship between experience and complication rate

To investigate the evidence for the relationship between volume and outcome for carotid artery stenting. We performed a systematic review of the literature to examine the influence of experience and/or volume on outcome for carotid artery stenting. The primary search strategy was to identify studies presenting year-on-year data. The Pubmed, Embase, Medline and the Cochrane Collaboration databases were searched. Studies with over 100 interventions were included. The main outcome measure compared across studies was all stroke/death. Where possible, comparable data were pooled and analysed using meta-regression techniques. It was not possible to perform a standard systematic review and meta-analysis because of the lack of data from randomised studies. When redundant studies were excluded, four sizeable case series and one registry met the inclusion criteria. When the case series results were pooled, the χ2-test for trend demonstrated a significant reduction in the combined stroke and death rate over time. Meta-regression analysis of case series data allowed the setting of thresholds for ‘acceptable’ stroke/death rates. Where year-on-year data are available, published stroke and death rates for carotid artery stenting show improvements over time. While advances in technology and pharmacology may in part be responsible, temporal improvement in outcomes demonstrated in both early and contemporary time-frames together with the consistency of the results suggests the presence of a learning curve. In active carotid artery stenting units, it may take almost 2-years before the stroke/death rates fall below an arbitrary 5% threshold.

Platelet Function Following Acute Cerebral Ischemia

Background: Studies have previously identified increased levels of platelet activation following acute ischemic stroke. In order to evaluate new antiplatelet agents and their combinations, there is a need for accurate measures of platelet activation. Methods: Blood was taken from 17 patients within 24 hours of an acute ischemic stroke, and then at 3, 7, 14 and 42 days. For comparison, a group of 18 stable arteriopaths had identical tests performed. Platelet aggregation was measured using a free platelet counting technique, and platelet surface P-selectin and monocyte platelet aggregates (MPAs) were measured using flow cytometry. Soluble P-selectin and D-dimers were measured by an enzyme linked immune assay. Results: The initial level of MPAs was significantly raised in the stroke patients compared with the stable patients (p = 0.04, 14.2% vs. 9.3%); however, this difference was not significantly higher than later study points (14.2%, 10.1%, 9.3%, 11.9%, 11.3%; days 1, 3, 7, 14 and 42 respectively. Day 1 vs. day 7 p = 0.07 ANOVA). No changes in P-selectin or platelet aggregation were identified. D-dimer levels were significantly higher on day 7 than day 42 (p < 0.01), and fibrinogen levels were elevated on both days 3 and 14 compared with day 42. Fibrinogen levels were not elevated compared with stable patients. Conclusions: MPA levels are elevated following an acute ischemic stroke compared to stable patients, but no significant change was seen with other platelet markers. This study suggests MPAs are a more sensitive marker of platelet activation than either P-selectin or aggregation.

Soluble but not platelet P-selectin correlates with spontaneous platelet aggregation: a pilot study.

Background. P-selectin (PS) is a marker of platelet activation measured on the platelet surface as platelet PS (pPS) or in serum as soluble PS (sPS). Controversy remains over the exact relationship between sPS, pPS, and other markers such as spontaneous platelet aggregation (SPA). Objective. To investigate correlations between pPS, sPS, and SPA in patients with peripheral arterial disease. Methods. SPA, pPS, and sPS levels were measured in venous blood sampled from patients following intermittent claudication (n = 18) or an acute stroke (n = 18). Results. SPA and sPS correlated significantly in the claudicants (Pearson correlation coefficient, r = 0.661; P = .0020) and stroke patients (r = 0.514; P = .020). No significant correlation was identified between pPS and SPA, or sPS and pPS. Conclusions. The 2 methods of assessing PS are not comparable. Although pPS is accepted as a platelet activation marker, sPS may be a better indicator of aggregation represented by SPA.

Treadmill exercise in claudicants on aspirin results in improved antioxidant status but only minimal platelet activation

The consequence of exercise on platelets remains controversial and adverse effects may result from repeated ischaemia reperfusion injury. We investigated platelet activation (platelet P-selectin (PS), and activated glycoprotein (Gp) IIb/IIIa), platelet–monocyte aggregates (PMA) and total plasma antioxidant status (TPAS) in claudicants after exercise. Twenty claudicants, taking 75 mg of aspirin daily, were subjected to repeated treadmill testing (3 km/h, 10% inclination). Blood was sampled before and after exercise. Activated GpIIb/IIIa, PS and PMA were quantified with flow cytometry. TPAS was quantified using a decolourisation assay. Percent positive cells for PS (pre-exercise 3.76% vs. 40 min post-exercise 4.10%; P < 0.05) and platelet–monocyte aggregates (pre-exercise: 25.31% vs. 40 min post-exercise 26.99%; P < 0.05) were significantly higher after exercise. Relative median fluorescence (RMF) for activated GpIIb/IIIa was significantly higher 40 min after exercise (pre-exercise: 3.04 vs. 40 min post-exercise: 4.01; P < 0.05). TPAS was significantly higher post-exercise (pre-exercise: 1.31 mmol/l vs. 1 min post-exercise: 1.40 mmol/l and 40 min post-exercise: 1.38 mmol/l; P < 0.01). Following moderate exercise, ‘aspirin treated claudicants’ show marginal platelet activation, PMA formation and a favourable improvement in antioxidant status. Further studies are required to assess the effect of additional antiplatelet agents and the significance of platelet–monocyte interactions. The possibility that aspirin contributes to the TPAS changes following exercise needs to be investigated.

MRSA infected pseudoaneurysms of the radial artery

The use of radial artery catheters for real-time blood pressure monitoring and arterial blood gas sampling has become commonplace in both intensive care and high dependency units. Although this procedure is relatively safe, it can be complicated by local infection leading to pseudoaneurysm formation. In this report we describe three cases of pseudoaneurysm formation following prolonged radial catheter placement, with evidence of local methicillin resistant staphylococcus aureus (MRSA) infection. With the growing problem of in-hospital MRSA colonisation, the report aims to emphasize the need for vigilance for this complication and reinforce the importance of careful asepsis. In all cases the pseudoaneurysms were successfully treated with local ligation of the radial artery, without subsequent ischaemic complications. Allens test was performed to ensure sufficient collateral circulation prior to surgery.

Problem-based learning for surgical trainees.

Problem-based learning (PBL) represents an educational technique that many medical schools have adopted for their undergraduate curricula. This article discusses the application of PBL for surgical trainees.

Combined aspirin and cilostazol treatment is associated with reduced platelet aggregation and prevention of exercise-induced platelet activation

BACKGROUND Cilostazol has proven efficacy in increasing walking distance in claudicants, but it has not been demonstrated to be more effective than placebo in secondary cardiovascular prevention. The direct effect of exercise on platelet function remains less well defined. We have investigated the effect of combination treatment with aspirin and cilostazol on platelet activity in claudicants subjected to repeated treadmill exercise. METHODS Nineteen claudicants completed a double-blind, randomised, controlled, cross-over trial. Each subject received a 2-week course of aspirin (75mg) and placebo and aspirin and cilostazol (100mg twice daily). Following each 2-week treatment period, patients participated in a standardised treadmill test (3.2kmh(-1), 10 degrees incline) walking to maximal claudication distance. The exercise was repeated thrice in total, and blood was sampled before and after exercise. Platelet activation was measured using free platelet counting aggregation, flow cytometry for surface markers of platelet activation and soluble P-selectin assay. RESULTS Compared to aspirin and placebo, combination treatment with aspirin and cilostazol was associated with reduced arachidonic-acid-induced platelet aggregation (p<0.01, Wilcoxon signed-rank test). Aspirin and placebo treatment were associated with elevated P-selectin expression, platelet-monocyte aggregation and reduced CD42b expression (p<0.05, Wilcoxon signed-rank test) post-exercise. No difference was seen in spontaneous platelet aggregation whilst soluble P-selectin was reduced post-exercise with combination treatment with aspirin and cilostazol (p<0.05, Wilcoxon signed-rank test). CONCLUSIONS Combination treatment with aspirin and cilostazol results in suppression of platelet activation and reduces the effect of exercise on platelets. The benefit seen may be a result of cilostazol enhancing the inhibitory effect of aspirin on the cyclo-oxygenase pathway.

Oral antiplatelet agents and bleeding risk in relation to major cardiovascular surgery.

INTRODUCTION Patients requiring major cardiovascular surgery are likely to be prescribed antiplatelet agents either alone or in combination. By virtue of antiplatelet agent effect, they can potentially increase bleeding complications, especially if used in combination. This article aims to review the evidence and make appropriate recommendations regarding these agents. ASPIRIN 16 papers are reviewed which concern surgery whilst taking aspirin. The bulk of the evidence is from the coronary bypass setting. CLOPIDOGREL: 14 papers are reviewed which concern surgery whilst taking clopidogrel. DIPYRIDAMOLE 2 papers are reviewed concerning dipyridamole. CILOSTAZOL: No trials are available concerning surgery and cilostazol. Several relevant publications are reviewed. CONCLUSION It is the recommendation of the authors that aspirin should usually be continued perioperatively, whilst clopidogrel should be stopped for seven days prior to surgery if at all possible.

Vascular surgery: operating on patients on clopidogrel or warfarin:

It is now generally accepted that aspirin can be continued during the perioperative period unless particular concerns exist over the risks of adverse bleeding. The main controversy confronting the vascular surgeon surrounds the perioperative management of patients on warfarin or clopidogrel. Both of these agents are frequently encountered in the population of patients that require vascular surgery. The common indications for warfarin therapy include prevention of thromboembolism (TE) in patients with atrial fibrillation (AF) and those with prosthetic heart valves. Clopidogrel is frequently used in combination with aspirin for enhanced antiplatelet therapy following acute coronary syndromes or percutaneous coronary interventions, and alone in those patients intolerant of aspirin. The high prevalence of more generalized vascular disease affecting the aortic, carotid and peripheral circulation in this elderly population means they often require vascular surgical intervention. At this time the surgeon must weigh up the beneficial effects of continuing warfarin or clopidogrel (antithrombotic) versus the perceived risks (problematic bleeding). With this information in mind the surgeon must decide on a drug strategy for the perioperative period. Unfortunately, the data available to enter into this risk–benefit equation may not be readily available on an individual patient basis, and may need to be extrapolated from other situations. The aim of this review is to examine the data available and produce practical management strategies for the perioperative use of clopidogrel and warfarin.