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1.  Current issues in patient adherence and persistence: focus on anticoagulants for the treatment and prevention of thromboembolism 
Warfarin therapy reduces morbidity and mortality related to thromboembolism. Yet adherence to long-term warfarin therapy remains challenging due to the risks of anticoagulant-associated complications and the burden of monitoring. The aim of this paper is to review determinants of adherence and persistence on long-term anticoagulant therapy for atrial fibrillation and venous thromboembolism. We evaluate what the current literature reveals about the impact of warfarin on quality of life, examine warfarin trial data for patterns of adherence, and summarize known risk factors for warfarin discontinuation. Studies suggest only modest adverse effects of warfarin on quality of life, but highlight the variability of individual lifestyle experiences of patients on warfarin. Interestingly, clinical trials comparing anticoagulant adherence to alternatives (such as aspirin) show that discontinuation rates on warfarin are not consistently higher than in control arms. Observational studies link a number of risk factors to warfarin non-adherence including younger age, male sex, lower stroke risk, poor cognitive function, poverty, and higher educational attainment. In addition to differentiating the relative impact of warfarin-associated complications (such as bleeding) versus the lifestyle burdens of warfarin monitoring on adherence, future investigation should focus on optimizing patient education and enhancing models of physician–patient shared-decision making around anticoagulation.
PMCID: PMC2846139  PMID: 20361065
anticoagulation; warfarin; adherence; persistence; thromboembolism
2.  Aspirin for elective hip and knee arthroplasty: a multimodal thromboprophylaxis protocol 
International Orthopaedics  2012;36(10):1995-2002.
Purpose
Multimodal thromboprophylaxis includes preoperative thromboembolic risk stratification and autologous blood donation, surgery performed under regional anaesthesia, postoperative rapid mobilisation, use of pneumatic compression devices and chemoprophylaxis tailored to the patient’s individual risk. We determined the 90-day rate of venous thromboembolism (VTE), other complications and mortality in patients who underwent primary elective hip and knee replacement surgery with multimodal thromboprophylaxis.
Methods
A total of 1,568 consecutive patients undergoing hip and knee replacement surgery received multimodal thromboprophylaxis: 1,115 received aspirin, 426 received warfarin and 27 patients received low molecular weight heparin and warfarin with or without a vena cava filter.
Results
The rate of VTE, pulmonary embolism, proximal deep vein thrombosis (DVT) and distal DVT was 1.2, 0.36, 0.45 and 0.36 %, respectively, in patients who received aspirin. The rates in those who received warfarin were 1.4, 0.9, 0.47 and 0.47 %, respectively. The overall 90-day mortality rate was 0.2 %.
Conclusions
Multimodal thromboprophylaxis in which aspirin is administered to low-risk patients is safe and effective following primary total joint replacement.
doi:10.1007/s00264-012-1588-4
PMCID: PMC3460073  PMID: 22684546
3.  Pharmacologic Reversal of Warfarin-Associated Coagulopathy in Geriatric Patients With Hip Fractures 
Purpose: Patients with acute hip fractures who are on maintenance warfarin for anticoagulation present a significant challenge and their management remains controversial. The purpose of this study was to assess thromboembolic and systemic complications associated with pharmacological reversal of warfarin-associated coagulopathy in a population of geriatric patients with hip fractures. Methods: This retrospective cohort study identified patients with operative hip fractures on oral warfarin therapy who had an international normalized ratio (INR) >1.50 on admission (N = 93) approximately over a 13-year span. The control group consisted of patients whose warfarin was held upon admission without further intervention preoperatively (n = 23). The treatment group consisted of patients who underwent pharmacologic reversal of elevated INR with vitamin K and/or fresh frozen plasma (FFP) in addition to holding warfarin (n = 70). Primary outcomes included thromboembolic and other complications as well as mortality within 3 months of presentation. Time to surgery was a secondary outcome. Results: The 3-month mortality rate was 4% in the pharmacological intervention group and 17% in the watch-and-wait group; this difference trended toward statistical significance (P = .06). There were no significant differences in the likelihoods of other thromboembolic or nonthromboembolic complications between groups. While the difference in mean time to surgery was not significantly different overall between groups, this difference was significant in a subgroup of patients with higher baseline INRs (n = 46, INR >2.17), with a mean difference of 4.0 fewer days until surgery in the pharmacological intervention group (P < .01). Conclusions: Pharmacological reversal of warfarin-associated coagulopathy with a combination of vitamin K and FFP appears to be a safe way to optimize patients for operative fixation of hip fractures and is associated with a shorter delay to surgery in patients with more elevated INRs preoperatively. Level of evidence: retrospective cohort study (level III).
doi:10.1177/2151458511417434
PMCID: PMC3597317  PMID: 23569682
anticoagulation; warfarin; reversal; hip fracture
4.  Antithrombotic Therapy in Patients with Prosthetic Heart Valves 
Patients with mechanical valve prostheses require a lifelong anticoagulant treatment. The combined use of Warfarin and low-dose aspirin appears to reduce the risk of valve thrombosis and systemic embolism at a low risk of bleeding. The management of women with prosthetic heart valves during pregnancy poses a particular challenge, as there are no available controlled clinical trials to provide guidelines for effective antithrombotic therapy. Oral anticoagulants, such as Warfarin, cause foetal embryopathy; unfractionated heparin and low-molecular-weight heparin have been reported to be ineffective in preventing thromboembolic complications. This article discusses the available data and the most recent guidelines in the antithrombotic management of patients with prosthetic valves, and antithrombotic therapy in various clinical situations such as pregnant women with prosthetic heart valves, and patients with prosthetic heart valves undergoing noncardiac surgery.
doi:10.4176/090115
PMCID: PMC3066703  PMID: 21483507
Anticoagulation; Valve disease; Valve prosthesis
5.  Antithrombotic therapy in atrial fibrillation: aspirin is rarely the right choice 
Postgraduate Medical Journal  2013;89(1052):346-351.
Atrial fibrillation, the commonest cardiac arrhythmia, predisposes to thrombus formation and consequently increases risk of ischaemic stroke. Recent years have seen approval of a number of novel oral anticoagulants. Nevertheless, warfarin and aspirin remain the mainstays of therapy. It is widely appreciated that both these agents increase the likelihood of bleeding: there is a popular conception that this risk is greater with warfarin. In fact, well-managed warfarin therapy (INR 2-3) has little effect on bleeding risk and is twice as effective as aspirin at preventing stroke. Patients with atrial fibrillation and a further risk factor for stroke (CHA2DS2-VASc >0) should therefore either receive warfarin or a novel oral agent. The remainder who are at the very lowest risk of stroke are better not prescribed antithrombotic therapy. For stroke prevention in atrial fibrillation; aspirin is rarely the right choice.
doi:10.1136/postgradmedj-2012-131386
PMCID: PMC3664370  PMID: 23404744
Atrial Fibrillation; Aspirin; Antithrombotic; Anticoagulant; Warfarin
6.  Evidence-based study on antithrombotic therapy in patients at risk of a stroke with paroxysmal atrial fibrillation 
The aim of the present study was to determine the optimal intensity of anticoagulation therapy in elderly patients with paroxysmal atrial fibrillation (PAF), using aspirin and varied concentrations of warfarin. Elderly patients with PAF (n=1,162) who met the inclusion criteria of the study and were at middle or high-risk of a stroke were investigated. Patients were divided into six groups (four high-risk groups and two middle-risk groups). Patients were treated with aspirin or varied concentrations of warfarin. The primary endpoint events, secondary endpoint events, major bleeding events and minor bleeding events were observed and compared. In high-risk elderly patients, warfarin significantly reduced primary and secondary endpoint events, total primary events and total events compared with aspirin. In middle-risk elderly patients, for all the events warfarin demonstrated no significant difference compared with aspirin. In high-risk patients with PAF, when the concentration of warfarin was adjusted to target international normalized ratio (INR) range 1.7–2.5, the primary and secondary endpoint events, total primary events and total events were significantly lower (P<0.05), compared with aspirin and warfarin at INR 1.2–1.6. When the intensity of warfarin was adjusted to the target INR 2.6–3.0, the primary and secondary endpoint events were significantly lower (P<0.05) compared with aspirin and warfarin INR at 1.2–1.6. This study determined that in high-risk elderly patients with PAF, warfarin is recommended for anticoagulation with an optimal INR range of 1.7–2.5. In patients at a middle-risk of a stroke, aspirin is the recommended treatment as an antithrombotic as results have indicated that there is limited benefit in the use of warfarin.
doi:10.3892/etm.2013.1141
PMCID: PMC3787006  PMID: 24137200
paroxysmal atrial fibrillation; aspirin; warfarin; middle risk; high risk
7.  Anticoagulation for non-valvular atrial aibrillation – towards a new beginning with ximelagatran 
Objectives
Ximelagatran is a novel oral direct thrombin inhibitor. It has favorable pharmacodynamic properties, with a broad therapeutic range without the need for anticoagulation monitoring. We aimed to discover whether ximelagatran offers a genuine future replacement to warfarin for patients in persistent atrial fibrillation (AF).
Materials and methods
We provide an evidence-based review of the relative merits and disadvantages of warfarin and aspirin. We subsequently present an overview of the evidence for the utility of ximelagatran in the treatment of AF.
Results
Adjusted dose warfarin is recommended over aspirin for patients in AF at high risk of future stroke. Some of this benefit is partially offset by the higher bleeding risks associated with warfarin therapy. The SPORTIF III and V studies have shown that ximelagatran is not inferior to warfarin in the prevention of all strokes in patients with AF (both persistent and paroxysmal). This benefit was partially offset by the finding of a significant elevation of liver transaminases (>3 × normal) in 6% of patients.
Conclusions
Current data would suggest that ximelagatran might represent a future alternative to warfarin. The lack of need for anticoagulant monitoring has been partially offset by a need for regular monitoring of liver function. Further data from randomized clinical trials is clearly needed.
doi:10.1186/1468-6708-5-3
PMCID: PMC420263  PMID: 15104801
8.  The safety and adequacy of antithrombotic therapy for atrial fibrillation: a regional cohort study 
Background
Atrial fibrillation is a common problem in older people. The evidence base for the safety of warfarin and aspirin in atrial fibrillation is largely derived from selective research studies and secondary care. Further assessment of the safety of warfarin in older people with atrial fibrillation in routine primary care is needed.
Aim
To measure the complication rates and adequacy of warfarin control in a cohort of patients with atrial fibrillation managed in primary care and compare them with published data from controlled trials and community patients with atrial fibrillation not receiving warfarin.
Design of study
Retrospective review of regional cohort.
Setting
Twenty-seven general practices in southwest Scotland.
Method
Case note review of 601 patients previously identified as having atrial fibrillation by GPs.
Results
The average age of our cohort was 77 years at recruitment. Two hundred and sixty-four (44%) patients died within 5 years of follow up. Three hundred and nine of the 601 (51%) patients with atrial fibrillation took warfarin at some stage during this study. INR (international normalised ratio) was maintained between 2 and 3 for 68% of the time. Bleeding risk was higher in patients taking warfarin than in those on aspirin or no antithrombotic therapy (warfarin 9.0% per year versus aspirin 4.7% per year versus no therapy 4.6% per year). The annual risk of any bleeding complication on warfarin (9%) was similar to that recorded in randomised trials (9.2%) whereas the annual risk of severe bleeding was approximately double (2.6 versus 1.3%).
Conclusion
Adequacy of anticoagulant control was broadly comparable to that reported in clinical trials, whereas the risk of severe bleeding was higher, possibly reflecting the older age and the comorbidities of our unselected cohort.
PMCID: PMC1876637  PMID: 16954003
anticoagulation; antithrombotic therapy; atrial fibrillation; cohort study
9.  Triple antithrombotic therapy in patients with atrial fibrillation undergoing coronary artery stenting: hovering among bleeding risk, thromboembolic events, and stent thrombosis 
Thrombosis Journal  2012;10:22.
Dual antiplatelet treatment with aspirin and clopidogrel is the antithrombotic treatment recommended after an acute coronary syndrome and/or coronary artery stenting. The evidence for optimal antiplatelet therapy for patients, in whom long-term treatment oral anticoagulation is mandatory, is however scarce. To evaluate the safety and efficacy of the various antithrombotic strategies adopted in this population, we reviewed the available evidence on the management of patients receiving oral anticoagulation, such as a vitamin-k-antagonists, referred for coronary artery stenting.
Atrial fibrillation is the most frequent indication for oral anticoagulation. The need of starting antiplatelet therapy in this clinical scenario raises concerns about the combination to choose: triple therapy with warfarin, aspirin, and a thienopyridine being the most frequent and advised. The safety of this regimen appeared suboptimal because of an increased risk in hemorrhagic complications. On the other hand, the combination of oral anticoagulation and an antiplatelet agent is suboptimal in preventing thromboembolic events and stent thrombosis; dual antiplatelet therapy may be considered only when a high hemorrhagic risk and low thromboembolic risk are perceived. Indeed, the need for prolonged multiple-drug antithrombotic therapy increases the bleeding risks when drug eluting stents are used.
Since current evidence derives mainly from small, single-center and retrospective studies, large-scale prospective multicenter studies are urgently needed.
doi:10.1186/1477-9560-10-22
PMCID: PMC3502192  PMID: 23075316
Atrial fibrillation; Percutaneous coronary intervention; Stent; Warfarin; Antiplatelet drugs
10.  Oculoplastic aspects of ocular oncology 
Eye  2012;27(2):199-207.
It is estimated that 5–10% of all cutaneous malignancies involve the periocular region and management of periocular skin cancers account for a significant proportion of the oculoplastic surgeon's workload. Epithelial tumours are most frequently encountered, including basal cell carcinoma, squamous cell carcinoma, and sebaceous gland carcinoma, in decreasing order of frequency. Non-epithelial tumours, such as cutaneous melanoma and Merkel cell carcinoma, rarely involve the ocular adnexae. Although non-surgical treatments for periocular malignancies are gaining in popularity, surgery remains the main treatment modality and has as its main aims tumour clearance, restoration of the eyelid function, protection of the ocular surface, and achieving a good cosmetic outcome. The purpose of this article is to review the management of malignant periocular tumours, with particular emphasis on surgical management.
doi:10.1038/eye.2012.243
PMCID: PMC3574244  PMID: 23196649
eyelid neoplasms; cryotherapy; radiotherapy; Mohs surgery; reconstruction
11.  Occult glove perforation during ophthalmic surgery. 
We examined the latex surgical gloves used by 56 primary surgeons in 454 ophthalmic surgical procedures performed over a 7-month period. Of five techniques used to detect pinholes, air inflation with water submersion and compression was found to be the most sensitive, yielding a 6.80% prevalence in control glove pairs and a 21.8% prevalence in postoperative study glove pairs, for a 15.0% incidence of surgically induced perforations (P = 0.000459). The lowest postoperative perforation rate was 11.4% for cataract and intraocular lens surgery, and the highest was 41.7% for oculoplastic procedures. Factors that correlated significantly with the presence of glove perforations as determined by multiple logistic regression analysis were oculoplastic and pediatric ophthalmology and strabismus surgical procedures, surgeon's status as a fellow in training, operating time, and glove size. The thumb and index finger of the nondominant hand contained the largest numbers of pinholes. These data suggest strategies for reducing the risk of cross-infection during ophthalmic surgery.
PMCID: PMC1298427  PMID: 1494836
12.  UK national survey of enucleation, evisceration and orbital implant trends 
Aim
To evaluate current clinical practice in the UK in the management of the anophthalmic socket; choice of enucleation, evisceration, type of orbital implant, wrap, motility pegging and complications.
Methods
All consultant ophthalmologists in the UK were surveyed by postal questionnaire. Questions included their practice subspecialty and number of enucleations and eviscerations performed in 2003. Specific questions addressed choice of implant, wrap, motility pegging and complications.
Results
456/896 (51%) consultants responded, of which 162 (35%) had a specific interest in oculoplastics, lacrimal, orbits or oncology. Only 243/456 (53%) did enucleations or eviscerations. 92% inserted an orbital implant after primary enucleation, 69% after non‐endophthalmitis evisceration, whereas only 43% did so after evisceration for endophthalmitis (50% as a delayed procedure). 55% used porous orbital implants (porous polyethylene, hydroxyapatite or alumina) as their first choice and 42% used acrylic. Most implants inserted were spherical, sized 18–20 mm in diameter. 57% wrapped the implant after enucleation, using salvaged autogenous sclera (20%), donor sclera (28%) and synthetic Vicryl or Mersilene mesh (42%). A minority (7%) placed motility pegs in selected cases, usually as a secondary procedure. 14% of respondents reported implant exposure for each type of procedure and extrusion was reported by 4% after enucleation and 3% after evisceration.
Conclusions
This survey highlights contemporary anophthalmic socket practice in the UK. Most surgeons use porous orbital implants with a synthetic wrap after enucleation and only few perform motility pegging.
doi:10.1136/bjo.2006.103937
PMCID: PMC1954760  PMID: 17151061
13.  Discontinuation of Warfarin Is Unnecessary in Total Knee Arthroplasty 
Patients with medical comorbidities that necessitate chronic anticoagulation therapy frequently present as candidates for total knee arthroplasty (TKA). We asked whether it was necessary to stop warfarin preoperatively to avoid postoperative bleeding complications. We retrospectively reviewed 77 preoperatively anticoagulated patients undergoing TKA. Thirty-eight of these 77 patients were maintained on their routine therapeutic warfarin regimen throughout the perioperative period. The remaining 39 patients had their routine preoperative warfarin regimen discontinued preoperatively and then restarted after surgery. We compared rates of comorbid illness, blood transfusions, wound complications, and reoperations. The demographic data and the ratio of primary to revision arthroplasties were similar in the two groups. The age-adjusted risk ratios for blood transfusions, wound complications, and reoperations were 0.61, 0.29, and 0.43, respectively. The data presented suggest maintaining a therapeutic warfarin regimen throughout the perioperative period for high-risk patients is not associated with an increase risk of complications after TKA.
Level of Evidence: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-009-1128-8
PMCID: PMC2795823  PMID: 19844768
14.  A net clinical benefit analysis of warfarin and aspirin on stroke in patients with atrial fibrillation: a nested case–control study 
Background
As the management of patients treated with anticoagulants and antiplatelet drugs entails balancing coagulation levels, we evaluated the net clinical benefit of warfarin and aspirin on stroke in a large cohort of patients with atrial fibrillation (AF).
Methods
A population-based cohort study of all patients at least 18 years of age with a first-ever diagnosis of chronic AF during the period 1993–2008 was conducted within the United Kingdom General Practice Research Database. A nested case–control analysis was conducted to estimate the risk of ischemic stroke and intracranial hemorrhage associated with the use of warfarin and aspirin. Cases were matched up to 10 controls on age, sex, and date of cohort entry. The adjusted net clinical benefit of warfarin and aspirin (expressed as the number of strokes prevented per 100 persons per year) was calculated by subtracting the ischemic stroke rate (prevented by therapy) from the intracranial hemorrhage (ICH) rate (increased by therapy).
Results
The cohort included 70,766 patients newly-diagnosed with chronic AF, of whom 5519 experienced an ischemic stroke and 689 an ICH during follow-up. The adjusted net clinical benefit of warfarin was 0.59 (95% CI: 0.45, 0.73). However, the benefit was not seen for patients below (0.08, 95%: -0.38, 0.54) and above (−0.49, 95% CI: -1.13, 0.15) therapeutic range. The net clinical benefit of warfarin, apparent after 3 months of continuous use, increased as a function of CHADS2 score. The net clinical benefit was not significant with aspirin (−0.07, 95% CI: -0.22, 0.08), though it was seen in certain subgroups.
Conclusions
Warfarin provides a net clinical benefit in patients with atrial fibrillation, which is maintained with longer duration of use, particularly when used within therapeutic range. A similar net effect is not as clear with aspirin.
doi:10.1186/1471-2261-12-49
PMCID: PMC3444325  PMID: 22734842
Atrial fibrillation; stroke; intracranial hemorrhage; warfarin; aspirin; net clinical benefit
15.  The postoperative bleeding rate and its risk factors in patients on antithrombotic therapy who undergo gastric endoscopic submucosal dissection 
BMC Gastroenterology  2013;13:136.
Background
There is a lack of consensus regarding the risk of postoperative hemorrhage in patients on antithrombotic therapy who undergo endoscopic submucosal dissection (ESD).
We examined postoperative bleeding rates and risk factors for postoperative hemorrhage from post-ESD gastric ulcers in patients on antithrombotic therapy.
Methods
The subjects of this study were 833 patients who underwent ESD of gastric tumors. Of these, 743 were not on antithrombotic therapy and 90 were on some form of antithrombotic therapy (46 on low-dose aspirin (LDA) only, 23 on LDA + thienopyridine, and 21 on LDA + warfarin). All patients commenced proton pump inhibitor (PPI) therapy immediately postoperatively. Antiplatelet agents were discontinued for 7 days preoperatively and postoperative Day 1, and anticoagulants for 5 days preoperatively and postoperative Day 1.
Results
The postoperative bleeding rate in the antithrombotic group was 23.3%, significantly higher than the 2.0% observed in the non-antithrombotic group. Significant differences were seen in patients in the antithrombotic group with and without postoperative bleeding according to ESD duration (p = 0.041), PPI + mucosal protective agent combination therapy (p = 0.039), and LDA + warfarin combination therapy (p < 0.001). Multivariate analysis of these factors yielded odds ratios of 1.04 for ESD duration, 14.83 for LDA + warfarin combination therapy, and 0.27 for PPI + mucosal protective agent combination therapy.
Conclusions
The risk of postoperative hemorrhage following gastric ESD was higher in patients with antithrombotic therapy than in those without that therapy. Among these patients, LDA + warfarin combination therapy and longer ESD duration were significant risk factors for postoperative bleeding. On the contrary, a mucosal protective agent to PPI therapy, lowering the odds ratio for postoperative bleeding, which suggests that the addition of a mucosal protective agent might be effective in preventing post-ESD hemorrhage in patients on antithrombotic therapy.
doi:10.1186/1471-230X-13-136
PMCID: PMC3844538  PMID: 24010587
Antithrombotic agents; Endoscopic submucosal dissection; Gastroprotective agent; Peptic ulcer; Proton-pump inhibitor
16.  Anticoagulation and atrial fibrillation. Putting the results of clinical trials into practice. 
Western Journal of Medicine  1995;163(2):145-152.
The thromboembolic risk of atrial fibrillation varies with the underlying cause, associated heart disease, and history of previous embolism. Decisions regarding warfarin anticoagulation therapy require a careful assessment of relative risks of thromboembolism and bleeding. Anticoagulation is strongly indicated for valvular atrial fibrillation and to prevent recurrent stroke in patients with atrial fibrillation and previous stroke or transient ischemic attack. Several randomized trials have consistently shown a reduction of the risk with the use of warfarin in nonvalvular atrial fibrillation, and anticoagulation is recommended. With a careful selection of patients, the risk of major bleeding on warfarin therapy is 2% to 4% per year. Aspirin therapy is less efficacious but also less risky than warfarin. Patients younger than 60 with lone atrial fibrillation do not require anticoagulation.
Images
PMCID: PMC1303009  PMID: 7571562
17.  Relationship between the Occurrence of Thromboembolism and INR Measurement Interval in Low Intensity Anticoagulation after Aortic Mechanical Valve Replacement 
Background
We investigated changes in the International Normalized Ratio (INR) and its measurement interval in patients with thromboembolic events who were treated by low intensity anticoagulation therapy after isolated mechanical aortic valve replacement.
Materials and Methods
Seventy-seven patients who underwent surgery from June 1990 to September 2006 were enrolled in the study and observed until August 2008. The patients were followed up at 4~8 week intervals and their warfarin (Coumadin)® dosage was adjusted aiming for a target range of INR 1.5~2.5. The rate of thromboembolic events was obtained. Changes in the mean INR and INR measurement interval were comparatively analyzed between the normal group (event free group, N=52) who had no anticoagulation-related complications and the thromboembolic group (N=10). Hospital records were reviewed retrospectively.
Results
The observation period was 666.75 patient-years. Thromboembolic events occurred in 10 patients. The linearized occurrence rate of thromboembolism was 1.50%/patient-years. Actuarial thromboembolism-free rates were 97.10±2.02% at 5 years, 84.30±5.22% at 10 years, and 67.44±12.14% at 15 years. The percentages of INR within the target range and mean INR were not statistically significantly different for the normal and thromboembolic groups. However, the mean INR during the segmented period just before the events showed a significantly lower level in the thromboembolic group (during a 4 month period: normal group, 1.86±0.14 vs. thromboembolic group, 1.50±0.28, p<0.001). The mean intervals of INR measurement during the whole observation period showed no significant differences between groups, but in the segmented period just before the events, the interval was significantly longer in thromboembolic group (during a 6 month period: normal group, 49.04±9.47 days vs. thromboembolic group, 65.89±44.88 days, p<0.01).
Conclusion
To prevent the occurrence of thromboembolic events in patients who receive isolated aortic valve replacement and low intensity anticoagulation therapy, we suggest that it would be safe to maintain an INR level above 1.8 and to measure the INR at least every 7~8 weeks.
doi:10.5090/kjtcs.2011.44.3.220
PMCID: PMC3249306  PMID: 22263155
Mechanical heart valve; Thromboembolism; Anticoagulation; INR measurement interval
18.  Anticoagulation therapy prevents portal-splenic vein thrombosis after splenectomy with gastroesophageal devascularization 
AIM: To compare the incidence of early portal or splenic vein thrombosis (PSVT) in patients treated with irregular and regular anticoagulantion after splenectomy with gastroesophageal devascularization.
METHODS: We retrospectively analyzed 301 patients who underwent splenectomy with gastroesophageal devascularization for portal hypertension due to cirrhosis between April 2004 and July 2010. Patients were categorized into group A with irregular anticoagulation and group B with regular anticoagulation, respectively. Group A (153 patients) received anticoagulant monotherapy for an undesignated time period or with aspirin or warfarin without low-molecular-weight heparin (LMWH) irregularly. Group B (148 patients) received subcutaneous injection of LMWH routinely within the first 5 d after surgery, followed by oral warfarin and aspirin for one month regularly. The target prothrombin time/international normalized ratio (PT/INR) was 1.25-1.50. Platelet and PT/INR were monitored. Color Doppler imaging was performed to monitor PSVT as well as the effectiveness of thrombolytic therapy.
RESULTS: The patients’ data were collected and analyzed retrospectively. Among the patients, 94 developed early postoperative mural PSVT, including 63 patients in group A (63/153, 41.17%) and 31 patients in group B (31/148, 20.94%). There were 50 (32.67%) patients in group A and 27 (18.24%) in group B with mural PSVT in the main trunk of portal vein. After the administration of thrombolytic, anticoagulant and anti-aggregation therapy, complete or partial thrombus dissolution achieved in 50 (79.37%) in group A and 26 (83.87%) in group B.
CONCLUSION: Regular anticoagulation therapy can reduce the incidence of PSVT in patients who undergo splenectomy with gastroesophageal devascularization, and regular anticoagulant therapy is safer and more effective than irregular anticoagulant therapy. Early and timely thrombolytic therapy is imperative and feasible for the prevention of PSVT.
doi:10.3748/wjg.v18.i26.3443
PMCID: PMC3396198  PMID: 22807615
Portal vein hypertension; Splenectomy with gastroesophageal devascularization; Portal or splenic vein thrombosis; Anticoagulation regimen; Thrombolytic therapy
19.  Should We Test for CYP2C9 Before Initiating Anticoagulant Therapy in Patients with Atrial Fibrillation? 
Background
Genetic variants of the warfarin sensitivity gene CYP2C9 have been associated with increased bleeding risk during warfarin initiation. Studies also suggest that such patients remain at risk throughout treatment.
Objective
Would testing patients with non-valvular atrial fibrillation (AF) for CYP2C9 before initiating warfarin improve outcomes?
Design
Markov state transition decision model.
Setting
Ambulatory or inpatient settings necessitating new initiation of anticoagulation.
Patients
The base case was a 69-year-old man with newly diagnosed non-valvular AF. Interventions included: (1) warfarin, (2) aspirin, or (3) no antithrombotic therapy without genetic testing; and genetic testing followed by (4) aspirin or (5) no antithrombotic therapy in those with culprit CYP2C9 alleles.
Measures
Quality-adjusted life years (QALYs).
Results
In the base case, testing and treating patients with CYP2C9*2 and/or CYP2C9*3 with aspirin rather than warfarin was best (8.97 QALYs). However, warfarin without genetic testing was a close second (8.96 QALYs), a difference of roughly 5 days. Sensitivity analyses demonstrated that genetic testing followed by aspirin was best for patients at lower risk of embolic events. Warfarin without testing was preferred if the rate of embolic events was greater than 5% per year, or the risk of major bleeding while receiving warfarin was lower.
Conclusion
For patients at average risk for ischemic stroke due to AF and at average risk for major hemorrhage, treatment based on genetic testing offers no benefit compared to warfarin initiation without testing. The gain from testing may be larger in patients at lower risk of embolic events or at greater risk of bleeding.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-009-0927-7) contains supplementary material, which is available to authorized users.
doi:10.1007/s11606-009-0927-7
PMCID: PMC2669861  PMID: 19255811
anticoagulant therapy; warfarin; genetic testing; pharmacogenetics; decision analysis; atrial fibrillation; stroke
20.  Experience versus complication rate in third molar surgery 
Head & Face Medicine  2006;2:14.
Objectives
The records of 1087 patients who underwent surgical removal of third molar teeth were prospectively examined to analyse the possible relationship between postoperative complications and the surgeon's experience parameter.
Method and materials
Seven surgeons (three specialists in surgical dentistry [specialists SD] and four oral and maxillofacial Senior House Officers [OMFS residents]) carried out the surgical procedures. For each patient, several variables were recorded including age, gender, radiographic position of extracted teeth, treating surgeon, duration of surgery and postoperative complications.
Results
Analysis of the data revealed some differences in the incidence of complications produced by the specialists SD and OMFS residents. The main statistically relevant differences were increase the incidences of trismus, nerve paraesthesia, alveolar osteitis and infection in the resident-treated group, while the specialist-treated group showed higher rates of post-operative bleeding.
Conclusion
The higher rate of postoperative complications in the resident-treated group suggests that at least some of the complications might be related to surgical experience.
Further work needs to compare specialists of training programmes with different years of experience, using large cross – sectional studies.
doi:10.1186/1746-160X-2-14
PMCID: PMC1481631  PMID: 16725024
21.  Aetiology and surgical treatment of childhood blepharoptosis 
The British Journal of Ophthalmology  2002;86(11):1282-1286.
Aims: To describe the aetiology, demography, surgical management, and outcome of a cohort of paediatric ptosis patients in a large tertiary referral oculoplastic centre.
Methods: A case note review of all patients undergoing ptosis surgery below the age of 16 years in a tertiary referral oculoplastic unit documenting the laterality, aetiology, severity of ptosis, indications for and type of surgery undertaken, the proportion of good, suboptimal, and poor surgical outcomes, re-operations, and level of patient satisfaction.
Results: 340 patients (82% (280/340) unilateral, 18% (60/340) bilateral ptosis) with myogenic (79%, 269/340), aponeurotic (5%, 16/340), neurogenic (11%, 37/340), mechanical (2%, 6/340), apparent (1%, 2/340), and syndrome related (3%, 10/340) ptosis underwent anterior (41%, 141/340) and posterior (26%, 90/340) levator resection, frontalis suspension with mersilene (9%, 29/340) and autogenous fascia lata (17%, 59/340), levator transposition (5%, 15/340) and other surgery (1%, 6/340) for visual (43%, 141/333) and cosmetic (57%, 189/333) indications. 77% (260/340) of patients achieved a good outcome, 10% (35/340) a suboptimal outcome, and 13% (45/340) a poor outcome requiring re-operation. There was no statistically significant difference in surgical outcome between patients with mild, moderate, or severe ptosis and with good, moderate, or poor levator function. The level of recorded patient satisfaction with the surgical outcome was 90% (206/229).
Conclusions: Results suggest that most groups of paediatric ptosis patients, including those with poor levator function and severe ptosis, achieve satisfactory results with the appropriate ptosis surgery.
PMCID: PMC1771363  PMID: 12386090
surgery; blepharoptosis; children
22.  Exploring barriers to optimal anticoagulation for atrial fibrillation: interviews with clinicians 
Background
Warfarin, the most commonly used antithrombotic agent for stroke prophylaxis in atrial fibrillation (AF), requires regular monitoring, frequent dosage adjustments, and dietary restrictions. Clinicians’ perceptions of barriers to optimal AF management are an important factor in treatment. Anticoagulation management for AF is overseen by both cardiology and internal medicine (IM) practices. Thus, gaining the perspective of specialists and generalists is essential in understanding barriers to treatment. We used qualitative research methods to define key issues in the prescription of warfarin therapy for AF by cardiology specialists and IM physicians.
Methods and results
Clinicians were interviewed to identify barriers to warfarin treatment in a large Midwestern city. Interviews were conducted until thematic saturation occurred. Content analysis yielded several themes. The most salient theme that emerged from clinician interviews was use of characteristics other than the patient’s CHADS2 score to enact a treatment plan, such as the patient’s social situation and past medication-taking behavior. Other themes included patient knowledge, real-world problems, breakdown in communication, and clinician reluctance.
Conclusion
Warfarin treatment is associated with many challenges. The barriers identified by clinicians highlight the unmet need associated with stroke prophylaxis in AF and the opportunity to improve anticoagulation treatment in AF. Social and lifestyle factors were important considerations in determining treatment.
doi:10.2147/JMDH.S33045
PMCID: PMC3426274  PMID: 22936848
anticoagulants; atrial fibrillation; risk factors
23.  Underutilization of antithrombotic therapy in atrial fibrillation. 
Most patients with atrial fibrillation should be considered for antithrombotic therapy. In a retrospective survey we investigated practice in two hospitals. For patients at high risk, established guidelines recommend warfarin, or aspirin if anticoagulants are contraindicated; for those at medium risk, either may be used. Of 156 with atrial fibrillation (acute, chronic or paroxysmal), 119 were at high risk, mean age 79 years. According to the guidelines, 89 of these were suitable for anticoagulation but only 49 (55%) received warfarin; 27 received aspirin and 13 neither. Of 27 patients at medium risk (mean age 70 years), 6 were not prescribed any antithrombotic therapy. This survey indicates that guidelines on antithrombotic therapy are commonly disregarded and that, in particular, warfarin is underutilized in the group for whom it is most indicated.
PMCID: PMC1297951  PMID: 10741314
24.  Low Risk of Thromboembolic Complications With Tranexamic Acid After Primary Total Hip and Knee Arthroplasty 
Background
The use of antifibrinolytic medications in hip and knee arthroplasty reduces intraoperative blood loss and decreases transfusion rates postoperatively. Tranexamic acid (TXA) specifically has not been associated with increased thromboembolic (TE) complications, but concerns remain about the risk of symptomatic TE events, particularly when less aggressive chemical prophylaxis methods such as aspirin alone are chosen.
Questions/purposes
We determined whether the rate of symptomatic TE events differed among patients given intraoperative TXA when three different postoperative prophylactic regimens were used after primary THA and TKA.
Methods
We retrospectively reviewed 2046 patients who underwent primary THA or TKA and received TXA from 2007 to 2009. The three chemical regimens included aspirin alone, warfarin (target international normalized ratio, 1.8–2.2), and dalteparin. Primary outcome measures were venous TE events, including symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), and arterioocclusive events, including myocardial infarction and cerebrovascular accident. Patients judged to be at high risk for TE due to recent cardiac stent placement or strong personal/family history of TE disease were excluded.
Results
For aspirin, warfarin, and dalteparin, the rates of symptomatic DVT (0.35%, 0.15%, and 0.52%, respectively) and nonfatal PE were similar (0.17%, 0.43%, and 0.26%, respectively). There were no fatal PE. Among the three groups, we found no difference in the rates of symptomatic DVT or PE with or without stratification by ASA score.
Conclusions
A low complication rate was seen when using TXA as a blood conservation modality during primary THA and TKA with less aggressive thromboprophylactic regimens such as aspirin alone and dose-adjusted warfarin.
Level of Evidence
Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-012-2488-z
PMCID: PMC3528901  PMID: 22814857
25.  Warfarin and Aspirin in Patients with Heart Failure and Sinus Rhythm 
The New England journal of medicine  2012;366(20):1859-1869.
BACKGROUND
It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm.
METHODS
We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause.
RESULTS
The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82).
CONCLUSIONS
Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized.
doi:10.1056/NEJMoa1202299
PMCID: PMC3723382  PMID: 22551105

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