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Copy-editor, Proofreader, good typist, translator Dutch to English
Italy - Last active: 4 months ago - Tests: 8 - Portfolio: 1
I have worked for 7 years in a private publishing/translations company. I worked as a manager so I have good experience working with people from many different nations. I have a good mastery of English and Dutch and can translate from Dutch into English. I am a quick and accurate typist and am an experienced and skilled proofreader and copy-editor. I have a knack for finding mistakes in text and have a passionate hatred for bad grammar and typographical errors in written material. I am not specifically experienced in freelancing but I am competent in my line of work, and I consider myself a perfectionist and capable of providing a good product. I would like an opportunity to freelance for a company that could hire me for a longer period of time. I also have some experience with Excell, MS Word, Powerpoint, etc. and can do office work and administrative functions. I have an orderly mind and a high stress threshold. I can deal with a lot random motion and still keep things under control.
Bookkeeper / Accountant
India - Last active: 1 day ago - Tests: 1
Education : Graduate - Bachelor of Commerce. Work Experience : Working as a Bookkeeper (Including Payroll) since 5 years. Accounting Softwares Worked - Quickbooks Online, QB Desktop Version, Lessaccounting, AMB(Acccounting for Mortgage Bankers), PC Lender. General ledger maintenance, Invoice processing, AP & AR, US Payroll, Inventory management and Bank Reconciliation. Processing Receipts and Deposits details. Monthly electronic Funds Transfers or check deposits reconciliation. General ledger: Entering and recording the new transactions, categorizing the expenses in the bank and Credit cards register. Review the transactions, entries whether posted to right account or not. Bank and credit card reconciliation: Monthly bank statements, Credit card statements reconciliation. Investigate & resolve any reconciliation variances. Bank charges is charged properly or not and Find our the any missing check numbers. Reports: Monthly financial statements - P&L, Balance sheet reports. AP aging reports. Payroll: Prepare employees attendance reports biweekly by using TimeTrax empoyees daily punches. Adding or deducting the working hours per client instructions. For Ex. In Time, Out Time conditions, Breaks, Over Time working hours, Vacations hours, Sick Holidays. Downloading the reports from Paychex website. Posting payroll and adjustment entries in the books of accounts. Preparing the 401k contribution report biweekly (Employees and Employer contributions) by using paychex payroll report and submit the 401k payment in online. Download the 401k submitted report and send it to client. 401K Annual online return filing in the month of July before 31st. Completing the Tasks or Jobs before the clients Timeline.
General Transcriptionist and Data Entry Specialist
United States - Last active: 1 day ago - Tests: 1
I Love Transcription and Data Entry! I am Self-Motivated, Detail-Oriented, and Hard-Working. I am very experienced with various types of data entry. Most recently I was the Product Specialist/Data Entry Clerk that was responsible for the products data being entered accurately to Magento, Excel, and Access. My transcription experience is with General Transcription, Verbatim and Non-Verbatim. My English is excellent: spelling is above average, grammar is average, but a high average. My Typing level is Advanced, 52 wpm, 99% accuracy. I am proficient with Microsoft Word, but highly capable of using other word processing software. I am versatile, experienced, knowledgeable, and a quick learner. I have high standards and produce excellent results.
- Transcription
- Microsoft Word
- English
- English Spelling
- Typing
- General Office Skills
- Microsoft Excel
- Magento
- Data Entry
- Accounts Payable Management
- Business Mathematics
- Product management
- Product Descriptions
- Proofreading
- Computer Skills
- Internet research
- Microsoft Publisher
- Office Administration
- Order processing
- Time Management
Customer Service Expert and Extremely Computer Proficient
United States - Last active: 1 day ago - Tests: 7 - Portfolio: 1
I am proficient in a variety of computer software programs and even hardware (including Quickbooks, Lawson Portal, Excel, Office, Outlook) as well as an extremely accurate and quick typist. I am experienced in handling general office duties, payroll, insurance claims (dental), office management and human resources, timecards, automated clock in and out systems, retail sales, and answering phones cordially and courteously. I've also handled all taxes for a business, A/P, handled cash, business budgeting, financial reports, credit card, and check payments and am an extremely quick learner when needed. You can always depend on me.
Experienced English to Vietnamese translator | Call center
Vietnam - Last active: 2 days ago - Tests: 3
I have bachelor degree in economics. My English is fluent while my Vietnamese is perfect. I have translated some documents and reports for some NGOs (from English to Vietnamese and Vietnamese to English also). I also had more than 1 year working in customer service department for a sports academy where I used English as my first laguage at work.
Massage Therapist/ Data Entry
United States - Last active: 1 month ago - Tests: 4
I have been a Massage Therapist for 9 years. Prior to that, I have experience with office work, data entry, and customer service, mainly in the field of Payroll processing; a job that I held for 4 years. I am a native English speaker, a fast typer and hold a BA in English Literature from the University of Massachusetts - Boston.
Virtual Assistant/Content Writer
South Africa - Last active: 4 days ago - Tests: 4 - Portfolio: 2
I am a Virtual/Personal Assistant and Content Writer with 4 years experience outside oDesk, I have key competencies in Office Administration, Project Management, Editing, Writing and Internet Research. My skills in Communication, particularly the English language – both verbal and written – are excellent. My work experience on oDesk is working on Voice Overs, Transcriptions, Office Administration and Writing Kindle Book Reviews.
Accountant that work as Business Controller
Indonesia - Last active: 6 days ago - Tests: 11 - Portfolio: 1
An Accountant that graduate from Universitas Padjadjaran (UNPAD) one of the best university in Indonesia, with 10+ years of experience on Finance & Accounting area & 6+ year in MNC as Business Controller Currently work in MNC manufacturing company & deal in excel, preparing and analyzing Financial reports, writing finance related articles, accounting, forecasting, valuation, business plans, etc.
Expert_Word_Execel, PDF_Data Entry_Photoshop_Illustrator_Web Search
Bangladesh - Last active: 1 day ago - Tests: 6 - Portfolio: 4
I have 10 years and above experience, I provide a variety of services related to Excel, Word data and PDF conversion (PDF to Word and Excel) and Editing. So to get done your job perfectly the following points deserve special attention. If you would like to get complicated and interactive Excel, Word and PDF with data processing, just share me.
Data Entry / Live Chat Support Specialist / V.A.- Admin. / Bookkeeper
Philippines - Last active: 5 hours ago - Tests: 2
Hardworking, dedicated and keen to details This is how I can describe myself in three words. I handled phone, e-mail and chat support jobs for the last 7 years. I also handled Quickbooks ( Intuit ) as a Level 2 Technical Support, helped customers with Accounting , as well as troubleshooting software application problems. Dishnetwork, AT &T Uverse, Phone , DSL , and Vonage , were some of the accounts I handled before.
Associated with: Consultancy Manila


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August 31, 2006
The Law School welcomes the Class of 2009. From August 30-September 1, students will participate in orientation activities. The class includes 255 students from 28 states and 5 foreign countries.
August 22, 2006
In Fall 2006, the Law School will add a 19th clinic, the Consumer Protection Clinic. Under the direction of Prentiss Cox, students will represent clients regarding marketplace fraud and consumer protection disputes.
August 17, 2006
The National Science Foundation awarded the Consortium on Law and Values in Health, Environment & the Life Sciences a 4-year, $1.22 million grant to develop oversight models for nanotechnology.
August 15, 2006
Edward "Dan" Robinson was featured in an article about his development of Intuit's Medical Expense Manager. His work with patient outreach groups and Intuit customers led him to join our Class of 2007.
Shell, author of Bargaining for Advantage and Director of the Wharton School Executive Negotiation Program will present a CLE workshop as part of the "Transactional Lawyering Skills Institute" 14-15 August.
August 2, 2006
The University of Minnesota Law School is delighted to announce a new Study Abroad exchange partnership with the University of Montevideo School of Law, Uruguay, commencing Fall 2006.
August 1, 2006
The Law School has completed its first J.D. Summer Program in Beijing. While in China, J.D. students studied comparative economic law, Mandarin Chinese, and the Chinese economic, legal, and political systems.
SCOTUS Cites Brief Co-Authored by Prof. Myron Orfield in Fair Housing Ruling
Robina Institute Launches Sentencing Guidelines Resource Center Website
Tax Clinic Wins 8th Circuit Appeal
Paul R. Scoggin ('84) Appointed Judge in Minnesota's 4th District
SCOTUS Immigration Victory for Innovative Law School Program: The Center for New Americans
Jack Baker ('72) and His Husband Profiled in New York Times
Law School Honors Class of 2015 at 127th Commencement Exercises
Khary Hornsby ('05) Receives Global Engagement Award
Law School Mourns the Passing of John D. Gould ('53)
Class of 2015 Students Honored at Awards Ceremony
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SUMMARY: Email marketing campaigns often drive traffic back to your team's website -- whether it's to check out new products or some great content you've added to your blog. Sometimes, though, your team needs its emails to pull a little extra weight in calling attention to your site.
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3:01 pm
Fri June 13, 2014
Jeb Hensarling Will Not Run For House Majority Leader
Originally published on Thu June 12, 2014 1:35 pm
Congressman Jeb Hensarling of Dallas says he has decided against running to replace Eric Cantor as House majority leader.
Hensarling announced his decision on Thursday. That leaves two candidates vying for the job of No. 2 House Republican leader: Pete Sessions of Dallas and Kevin McCarthy of California.
The leadership job opened Wednesday when Cantor said he'll step down as majority leader on July 31. Cantor was defeated Tuesday in the Virginia GOP primary by a little-known economics professor who was heavily backed by conservative voters.
House leadership elections will be held next Thursday.
Hensarling says he made his decision after prayerful reflection. He chairs the House Financial Services Committee.
As KERA reported earlier this week, Hensarling's name is on a list of possible successors to U.S. House Speaker John Boehner, who may step down after November's election.
Here's the statement Hensarling's office released Thursday:
"Although I am humbled by the calls, emails, and conversations from my colleagues encouraging me to return to leadership for the remainder of the 113th Congress, I will not be a candidate for Majority Leader next week. After prayerful reflection, I have come to the conclusion that this is not the right office at the right time for me and my family. I look forward to working with the new Majority Leader to fight for a freer, stronger, more prosperous America as Chairman of the Financial Services Committee and the Representative of the Fifth District of Texas."


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Internship: University of Michigan Hospitals, MI. Recognized by the National Committee for Quality Assurance and the American Diabetes Association for providing quality care to patients with diabetes.
Dr. Chen was voted "Top Doctors" in Seattle Metropolitan Magazine (2011, 2012)
Nearly 4,500 physicians, nurses and physician assistants in King, Kitsap and Snohomish counties nominated colleagues they would choose to treat themselves and their loved ones.
News Release
The Patient Rating score is based on responses given during the CAHPS Patient Experience Survey. Responses are measured on a 10-point scale, with 10 being the best score. These scores are then translated to a 5-point scale in order to display results in a 5-star rating. Comments are also gathered from the same survey and displayed in their entirety with the exception of any language that may be considered slander, libel or contain private health information, which will be removed prior to publishing the comments.
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In the five months since Cael Sanderson announced he was leaving the head coaching position at Iowa State for Penn State, many in the college wrestling community continue to ask why.
Was there a huge increase in salary? Was there friction in the athletic department in Ames, Iowa?
In an article written by Sean Keeler for the Des Moines Register, Sanderson attempted to address some of those issues.


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Reviewed By David G (SANTA MONICA, CA) Reviewed for a 1991 Land Rover Range Rover —12/2/2014 6:06 AM
I had these installed with new springs and the ride is amazing. Very happy with AutoAnything and my new shocks.
Reviewed By Gregory P (Boca Raton, FL) Reviewed for a 2007 Land Rover LR3 —10/30/2010 10:06 PM
The VIAIR 450 is one tough high performance machine. Airing the 19" tires on my LandRover LR3 is simply not a problem, all 4 in less than 4 minutes and it is running strong at 100%. It undoubtedly can handle larger jobs and will on my built-out Toyota LandCruiser FJ40 with 39" tires. Go VIAIR!!!


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thickeners Companies in Alaska
WesTech Engineering, Inc.
based in Salt Lake City, UTAH (USA)
WesTech Engineering, Inc. celebrates 40 years as a recognized leader in the manufacture of liquid/solids separation equipment for industrial and municipal process applications. Surface waters, groundwater, water reuse, drinking water, wastewater treatment and industrial process equipment and technologies designed to meet customer specifications, and exceed performance ...
PHOENIX Process Equipment Co.
based in Louisville, KENTUCKY (USA)
PHOENIX Process Equipment Co. designs and manufactures a variety of high quality systems for slurry and sludge thickening and dewatering; effluent water treatment; sand and frac sand processing; fine particle wet classification and separation; rainwater/stormwater/greywater/blackwater purification and recycling for commercial and multi-residence applications. The PHOENIX ...
AMCON Inc.
based in Yokohama, JAPAN
AMCON Inc., team of professionals of dewatering, provides rich variety dewatering equipment from low priced micro compact dewatering equipment to high-capacity king-size dewatering equipment to meet your request.
Hendrick Screen Co.
based in Owensboro, KENTUCKY (USA)
Leading manufacturer of wedge wire screens, intakes, diversion and fish screens, filter beds, static sieve screens and lateral flow thickeners.
ANDRITZ Separation - a division of the Andritz Group
based in Waddinxveen, NETHERLANDS
ANDRITZ Separation, trusted partner for process solutions for waste water treatment. There is a wide range of challenges in municipal drinking water and waste water treatment: whereas in developing countries the focus is often on setting up a base structure for drinking water and wastewater, in industrialized countries water quality, efficiency and recycling of residual ...
Ovivo (Formerly Eimco Water Technologies)
based in Salt Lake City, UTAH (USA)
Following the merger of Eimco Water Technologies, Enviroquip and Christ Water Technology, September 2010 sees the emergence of a new global force in the water sector, dedicated to bringing the latest thinking, proven technologies and the most advanced application knowledge to the municipal and industrial clean water, process water and wastewater markets around the globe. ...
Press Technology & Mfg., Inc.
based in Springfield, OHIO (USA)
Press Technology is a developer and manufacturer of cutting edge screw presses for pulp and paper, municipal waste and other industrial sludge dewatering applications. A leader in new screw press design, Press Technology specializes in developing and manufacturing equipment tailored to meet customer requirements and demands.
DWT Group Oy
based in LAITILA, FINLAND
DWT Group Oy, is an innovative company specialized in providing sophisticated range of DEWACO and CAVIA brand equipment & solutions for the sludge and waste water treatment in industries and municipalities. The product range includes a variety of belt thickeners, belt filter presses and chain and flight type sludge and scum collector equipments. Thanks to the recent ...
DRYCAKE - Vanderbeken Enterprises Ltd.
based in Quebec, QUEBEC (CANADA)
Distributor of CBB centrifuges, decanters, separators, and of conveyors, channel screens, bar screen, sludge dryers, grit removal, polymer systems, drum thickeners, and pumps. Specializing in small and medium sized plants. Compost, recycling, and solid waste handling equipment and plants. Fiberglass grating.DRYCAKE supplies dewatering centrifuges, sludge dryers, screens, ...
Toro Equipment S.L.
based in La Cistérniga, SPAIN
Toro Equipment is one of the principal companies specializing in the design and construction of machinery for the treatment and waste water treatment. The expansion of his activities has needed the search of new markets, up to forming a commercial international structure with presence in diverse countries. Our Equipments are manufactured to the highest standards and ...
Related Terms for thickeners
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Antiphospholipid antibodies predict imminent vascular events independently from other risk factors in a prospective cohort
Neville, Carolyn
Rauch, Joyce
Kassis, Jeannine
Solymoss, Susan
Joseph, Lawrence
Belisle, Patrick
Levine, Jerrold S.
Fortin, Paul R.
Thrombosis and haemostasis
Antiphospholipid antibodies (aPL) are associated with vascular events, but the magnitude of this risk, alone, or in combination with other atherogenic and thrombophilic risk factors, remains unclear. A prospective cohort of 415 persons was studied for arterial and venous events (AE and VE) over a median time of 7.4 years. aPL and coagulation abnormalities were measured upon beginning of the study and annually for the first four years. Within the cohort, a nested case-control study was conducted to investigate the role of endothelial and inflammatory markers in predicting new vascular events. Forty-five individuals had new vascular events: 18 occurred during the first year of follow-up. The proportion of event-free survivors at eight years was 90% (95%CI = 87%, 94%) for aPL-negative and 72% (60%, 85%) for aPL-positive individuals, respectively. Predictors for new AE were previous AE (HR=5.7 [2.7, 12.0]), diabetes (5.6 [2.4, 13.2]), aPL positivity (2.6 ([1.2, 5.9]), and age (1.04 [1.01, 1.07]). New VE were predicted by previous VE (6.1 [1.9, 19.9]), anti-β2-glyco-protein I (aβ2GPI) positivity (5.8 [1.4, 24.1]), activated protein C resistance (APCR) (4.1 [1.1, 15.1]), and gender (3.7 [1.1, 12.9]). In the nested case-control study, similar predictors were observed for AE, while abnormal APCR (OR=5.5 [1.1, 26.6]) and elevated von Willebrand factor (vWF) (OR=5.0 [1.2, 19.8]) best predicted VE. We demonstrate that aPL independently predict new vascular events and discriminate between individuals with and without events in the first two years of follow-up, indicating that aPL are associated with a short-term risk of developing new and recurrent vascular events.
Antiphospholipid antibodies; thrombosis; anti-beta2-glycoprotein I; activated protein C resistance; von Willebrand factor
Related Articles
High Antiphospholipid Antibody Levels are Associated with Statin Use and May Reflect Chronic Endothelial Damage in Non-Autoimmune Thrombosis: cross-sectional study
Broder, Anna
Tobin, Jonathan N.
Putterman, Chaim
Journal of clinical pathology
Persistently elevated antiphospholipid antibodies (aPL Ab) and positive lupus anticoagulant (LAC) are associated with an increased risk of thrombosis. Our objective was to explore whether aPL Ab and/or LAC positivity were associated with the traditional risk factors for thrombosis or with medication use in patients without autoimmune diseases hospitalized with arterial or venous thrombosis.
Cross-sectional study
Montefiore Medical Center, a large urban tertiary care center
Two hundred and seventy patients (93 with deep vein thrombosis (DVT) or pulmonary embolism (PE), and 177 with non-hemorrhagic stroke (CVA)) admitted between January 2006 and December 2010 with a discharge diagnosis of either DVT, PE or CVA, who had LAC and aPL Abs measured within six months from their index admission. We excluded patients with lupus or antiphospholipid syndrome.
Main Outcome Measures
The main dependant variable was aPL Ab ≥ 40 units (aPL Ab+) and/or LAC+. Independent variables: traditional thrombosis risk factors, statin use, aspirin use, and warfarin use.
Thirty one (11%) patients were LAC+ and/or aPL Ab+ (aPL/LAC+). None of the traditional risk factors at the time of DVT/PE/CVA was associated with aPL/LAC+. Current statin use was associated with an OR of 3.2 (95% CI 1.3, 7.9, p = 0.01) of aPL/LAC+, adjusted for age, ethnicity and gender. Aspirin or warfarin use was not associated with aPL Ab levels.
If statin therapy reflects the history of prior hyperlipidemia, high levels of aPL Abs may be a marker for prior endothelial damage caused by hyperlipidemia.
Antiphospholipid antibodies; statins; endothelial damage; thrombosis
Related Articles
Thromboembolic risk in patients with high titre anticardiolipin and multiple antiphospholipid antibodies
Neville, Carolyn
Rauch, Joyce
Kassis, Jeannine
Chang, Erika R.
Joseph, Lawrence
Le Comte, Martine
Fortin, Paul R.
Thrombosis and haemostasis
Asymptomatic antiphospholipid antibody (aPL) carriers with high risk for thrombosis may benefit from preventive anticoagulation.
It was our objective to test whether the risk of thrombosis increases with: 1) increasing titres of anticardiolipin antibodies (aCL) after adjustment for other cardiovascular risk factors and 2) the number of aPL detected.
In a cross-sectional study, blood was collected from clinics in two teaching hospitals. The study included 208 individuals suspected of having an aPL and 208 age- and sex-matched controls having blood drawn for a complete blood count.
Clinical variables included history of previous arterial (ATE) or venous (VTE) thrombotic events, traditional risk factors for cardiovascular disease, and systemic lupus erythematosus (SLE). Laboratory variables included IgG/IgM aCL, lupus anticoagulant, and IgG/IgM anti-β2-glycoprotein I.
Mean age was 46.5 years and 83% were female. Seventy-five of the 416 participants had ≥ 1 aPL, and 69 had confirmed ≥ 1 ATE or VTE. Family history was positive in 48% of participants, smoking in 28%, hypertension in 16%, diabetes in 6%, and SLE in 20%. A 10-unit increase in aCL IgG titre was associated with an odds ratio (OR) [95% CI] of 1.07 [1.01–1.13] for ATE and 1.06 [1.02 – 1.11] for VTE. The odds of a previous thrombosis increased with each additional aPL detected: 1.5 [0.93–2.3] for ATE and 1.7 [1.1–2.5] for VTE.
These results indicate that increased titres of aCL and multiple aPL were associated with an increased risk of a previous thrombotic event.
Antiphospholipid syndrome; antiphospholipid antibodies; anti-cardiolipin antibody; thrombosis
Related Articles
Prevalence of thrombophilic mutations in patients with unprovoked thromboembolic disease. A comparative analysis regarding arterial and venous disease
Mandala, E
Lafaras, C
Tsioni, C
Speletas, M
Papageorgiou, A
Kleta, D
Dardavessis, T
Ilonidis, G
Background: Thromboembolic disease (TED) represents one of the main reasons of morbitity and mortality in Western World. Venous and arterial thrombotic disorders have long been viewed as separate pathophysiological entities. However, in recent times the separate nature of arterial and venous thrombotic events has been challenged. Although inherited thrombophilia's predominant clinical manifestation is venous thrombosis, its contribution to arterial thrombosis remains controversial. Purpose of the study was to evaluate the prevalence of the most common thrombophilic mutations, FV Leiden G1691A-FVL and FII G20210A-PTM and to assess the differences between venous, arterial and mixed thrombotic events. Testing for polymorphism MTHFR C677T and antithrombin, protein C and protein S was also performed. Correlations with dyslipidemia, smoking, obesity, homocysteine and antiphospholipid antibodies were made.
Methods: 515 patients with unprovoked TED, 263 males, median age 44 years, were studied. Patients were divided into three groups: 258 with venous thrombosis (group A), 239 with arterial (group B) and 18 with mixed episodes (group C). All patients were interviewed regarding family history of TED, origin, smoking and dyslipidemia. Body mass index (BMI) had been calculated. Molecular assessment of the FVL, PTM and MTHFR C677T was performed. Antithrombin, protein C, protein S, APCR, homocysteine, antiphospholipid antibodies and lipid profile were also measured.
Results: The population studied was homogenous among three groups as regards age (p=0.943), lipid profile (p=0.271), BMI (p=0.506), homocysteine (p=0.177), antiphospholipid antibodies (p=0.576), and positive family history (p=0.099). There was no difference in the prevalence of FVL between venous and arterial disease (p=0.440). Significant correlation of PTM with venous TED was found (p=0.001). The number of positive and negative for MTHFR presented statistically significant difference with a support in arterial disease (p=0.05). Moreover, a 2-fold increase in the risk of venous thrombosis in FVL positive patients (odds ratio: 2.153) and a positive correlation of homocysteine levels with MTHFR C677T (p<0.001) was found.
Conclusions: Correlation of PTM with venous thrombosis was established. Analysis showed no difference in prevalence of FVL between venous and arterial thrombosis, indicating that FVL might be a predisposing factor for arterial disease. A significant increase in MTHFR C677T prevalence in arterial disease was found. In conclusion, young patients with unprovoked arterial disease should undergo evaluation for thrombophilic genes. Identification of these mutations is important in the overall assessment and management of patients at high risk. Findings will influence the decisions of stratified approaches for antithrombotic therapy either primary or secondary thromboprophylaxis, the duration of therapy, the potential for avoiding clinical thrombosis by risk factor modification and the genetic counselling of family members. However, further studies are needed to clarify the nature of the association regarding venous and arterial thrombotic events.
thrombophilic mutations; unprovoked thromboembolic disease; arterial thromboembolic disease; venous thromboembolic disease
Related Articles
Antiphospholipid antibodies (aPL) in systemic lupus erythematosus. Are they specific tools for the diagnosis of aPL syndrome?
Ghirardello, A
Doria, A
Ruffatti, A
Rigoli, A M
Vesco, P
Calligaro, A
Gambari, P F
Annals of the Rheumatic Diseases
OBJECTIVE--Antiphospholipid antibody (aPL) specificity for aPL-related events was evaluated in systemic lupus erythematosus (SLE). METHODS--A study was carried out on 105 patients affected with SLE comparing the prevalence of lupus anticoagulant (LA) and IgG and IgM anticardiolipin antibodies (aCL) between patients with and without features of antiphospholipid syndrome (APS). Antiphospholipid antibody profile was subsequently evaluated in the aPL positive patients with and without aPL-related events, thus excluding the patients with complications of APS possibly due to factors other than aPL. RESULTS--LA showed a strong association with thrombosis and livedo reticularis, and IgG aCL with thrombosis and neurological disorders, while no clinical features were associated with IgM aCL. A considerable number of aPL positive patients with no aPL-related manifestations was also observed, suggesting the low specificity of aPL assays (54.4%). When studying the 60 aPL positive patients, LA was specific (91.3%) for the diagnosis of aPL-related thrombosis, whereas aCL were not specific, although IgG aCL mean levels were higher in patients with arterial thrombosis than in those without APS features. CONCLUSIONS--LA but not aCL positivity is a specific tool for the diagnosis of thrombotic complications due to aPL in SLE.
Related Articles
Value of Isolated IgA anti-β2GPI Positivity in the Diagnosis of the Antiphospholipid Syndrome
Murthy, Vijaya
Willis, Rohan
Romay-Penabad, Zurina
Ruiz-Limón, Patricia
Martínez-Martínez, Laura A.
Jatwani, Shraddha
Jajoria, Praveen
Seif, Alan
Alarcón, Graciela S.
Papalardo, Elizabeth
Liu, Jigna
Vilá, Luis M.
McGwin, Gerald
McNearney, Terry A.
Maganti, Rashmi
Sunkureddi, Prashanth
Parekh, Trisha
Tarantino, Michael
Akhter, Ehtisham
Fang, Hong
Gonzalez, Emilio B.
Binder, Walter R.
Norman, Gary L.
Shums, Zakera
Teodorescu, Marius
Reveille, John D.
Petri, Michelle
Pierangeli, Silvia S.
Arthritis and rheumatism
To examine the prevalence of isolated IgA anti-β2Glycoprotein I (anti-β2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2GPI, with clinical manifestations of the Antiphospholipid Syndrome (APS) in three patients groups. The pathogenicity of IgA anti-β2GPI was also evaluated in a mouse model of thrombosis.
Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n=558), patients with SLE from the Hopkins Lupus Cohort (n=215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n=5,098) were evaluated. IgA anti-β2GPI titers and binding to domain IV/V of β2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti- β2GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity.
A total of 198 patients were found to be positive for IgA anti-β2GPI isotype, and 57 patients were positive exclusively for IgA anti-β2GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-β2GPI positive serum samples reacted with domain IV/V of anti-β2GPI, and 77% of those had clinical features of APS. Isolated IgA anti-β2GPI positivity was associated with an increased risk for arterial thrombosis (p<0.001), venous thrombosis (p=0.015) and all thrombosis (p<0.001). The association between isolated IgA anti-β2GPI and arterial thrombosis (p=0.0003) and all thrombosis (p=0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-β2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls.
Isolated IgA anti-β2GPI positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid (aPL) tests are negative and APS is suspected is recommended. IgA anti-β2GPI antibodies directed to domain IV/V of β2GPI represent an important subgroup of clinically relevant antiphospholipids.
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Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3.
Fishman, P
Falach-Vaknine, E
Zigelman, R
Bakimer, R
Sredni, B
Djaldetti, M
Shoenfeld, Y
Journal of Clinical Investigation
Antiphospholipid antibodies are strongly associated with arterial and venous thrombosis and with fetal loss. Recently an experimental model for antiphospholipid syndrome (APLS) was established in our laboratory. In this model, mice are immunized passively or actively with anticardiolipin antibodies and acquire the syndrome, which is characterized by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, low fecundity rate, and fetal loss. In a normal process of pregnancy, lymphokines affect fetal implantation and development. Cytokines from the colony stimulating factor family, like GM-CSF and IL-3, were shown to be positive signals for implantation and to promote placental development and fetal growth. Given our preliminary findings of low IL-3 in mice with APLS and the efficacy of IL-3 in preventing fetal loss in a strain of mice prone to fetal resorption, our aim in the present study was to examine the effect of murine recombinant IL-3 (mrIL-3) on pregnant mice induced with experimental APLS. Mice were passively transfused to the tail vein, 24 h following mating, with anticardiolipin antibodies. The mice were divided into two groups: one group was injected intraperitoneally with mrIL-3 on days 6.5, 8.5, and 10.5 after mating, while the control group was injected with PBS. When the mice were killed on day 15 of pregnancy a 32% +/- 4.2 resorption rate was observed in the anti-cardiolipin-immunized group, which was reduced to 4% +/- 0.3 following treatment with mrIL-3. The thrombocytopenia associated with the experimental APLS was also corrected following lymphokine administration. IL-3 may be effective in prevention of recurrent fetal loss in APLS.
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Patent foramen ovale, cardiac valve thickening and antiphospholipid antibodies as risk factors for subsequent vascular events: The PICSS-APASS Study
Rajamani, Kumar
Chaturvedi, Seemant
Jin, Zhezhen
Homma, Shunichi
Brey, Robin L
Tilley, Barbara C.
Sacco, Ralph L
Thompson, JLP
Mohr, JP
Levine, Steven R
Stroke; a journal of cerebral circulation
(1) Estimate risk of recurrent stroke/TIA/death in the subgroup of the Patent foramen ovale in the Cryptogenic Stroke Study (PICSS) cohort with patent foramen ovale (PFO) and antiphospholipid antibodies (aPL) and (2) Estimate risk of recurrent stroke/TIA/death in aPL positive patients who have thickened left-sided heart valves (VaT).
PFO is associated with cryptogenic ischemic stroke. Also, the presence of aPL is associated with ischemic cerebrovascular disease.
Combined data from 2 major sub studies of the Warfarin Aspirin Recurrent Stroke Trial (WARSS) were evaluated. PICSS subjects were included if they were enrolled in the Antiphospholipid Antibodies and Stroke Study (APASS) and had a baseline aPL test (lupus anticoagulant, anticardiolipin antibodies, or both) within one month of the stroke. All patients in PICSS underwent transesophageal echocardiography for PFO as well as VaT, which was performed blinded to aPL status and treatment arm (325mg/d aspirin or adjusted dose warfarin, target INR 1.4–2.8). The primary outcome event was the 2-year risk of recurrent stroke/TIA/death and was evaluated using Cox proportional hazards model. As there was no treatment effect, warfarin and aspirin groups were combined to increase power. For the combined endpoint, power to detect a HR of 2 was 47.8% for the PFO and aPL positive group, and 75.3% for the valve thickening and aPL positive group, assuming two-sided type I error of 0.05
525 subjects were tested for the combined presence of PFO and aPL and were available for evaluation. The primary outcome event rate was 23.9% (HR 1.39, 95% CI 0.75–2.59) in the PFO positive/aPL positive group, compared to 13.9% (HR 0.83, 95% CI 0.44–1.56) in the PFO positive/aPL negative group and 19.9% (HR 1.16 95% CI 0.68–1.90) in the PFO negative/aPL positive group.
545 subjects tested for combined presence of aPL and left sided cardiac VaT were available for evaluation. The primary event rate was 22.6% (HR1.65, 95% CI 0.88–3.09) in the VaT positive/aPL positive group, compared to 19.4% (HR 1.50, 95% CI 0.82–2.75) in the VaT positive/aPL negative group and 20.2% (HR 1.63, 95% CI 0.81–3.25) in the VaT negative /aPL positive group.
The combined presence of aPL with either a PFO or with left sided cardiac VaT did not significantly increase risk of subsequent cerebrovascular events in this PICCS/APASS cohort of patients.
patent foramen ovale; anti-phospholipid antibodies; cardiac valve thickening; stroke recurrence risk; stroke risk factors; Risk Factors
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Hydroxychloroquine Use is Associated with Lower Odds of Persistently Positive Antiphospholipid Antibodies and/or Lupus Anticoagulant in SLE
Broder, Anna
Putterman, Chaim
The Journal of rheumatology
Antiphospholipid antibodies (aPL Abs) play an active role in the pathogenesis of the antiphospholipid syndrome (APLS). Primary prevention in APLS may be aimed at decreasing existing elevated aPL Ab levels, or preventing high aPL titers and/or lupus anticoagulant (LAC) from developing in the first place. Hydroxychloroquine (HCQ) has been shown to decrease aPL titers in laboratory studies, and to decrease thrombosis risk in systemic lupus erythematosus (SLE) patients in retrospective studies. We investigated an association between HCQ use and persistent aPL Abs and/or LAC in SLE.
We identified all patients over 21 years old with SLE, from an urban tertiary care center, who had aPL Abs and LAC measured on at least 2 occasions, at least 12 weeks apart. We defined the presence of persistent LAC+ and/or at least one aPL Ab ≥ 40 units (IgA, IgG or IgM) as the main outcome variable.
Among 90 patients included in the study, 17 (19%) had persistent LAC+ and/or at least one aPL Ab ≥ 40 units. HCQ use was associated with significantly lower odds of having persistent LAC+ and/or aPL Abs ≥ 40 U, OR 0.21 (95% CI 0.05, 0.79) p=0.02, adjusted for age, ethnicity, and gender.
This is the first study to show that HCQ use is associated with lower odds of having persistently positive LAC and/or aPL Abs. Data from this study provides a basis for the design of future prospective studies investigating the role of HCQ in primary and secondary prevention of APLS.
Lupus Erythematosus, Systemic; Antiphospholipid Antibodies; Lupus Anticoagulant; Hydroxychloroquine
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Antiphospholipid syndrome; its implication in cardiovascular diseases: a review
Koniari, Ioanna
Siminelakis, Stavros N
Baikoussis, Nikolaos G
Papadopoulos, Georgios
Goudevenos, John
Apostolakis, Efstratios
Journal of Cardiothoracic Surgery
Antiphospholipid syndrome (APLS) is a rare syndrome mainly characterized by several hyper-coagulable complications and therefore, implicated in the operated cardiac surgery patient. APLS comprises clinical features such as arterial or venous thromboses, valve disease, coronary artery disease, intracardiac thrombus formation, pulmonary hypertension and dilated cardiomyopathy. The most commonly affected valve is the mitral, followed by the aortic and tricuspid valve. For APLS diagnosis essential is the detection of so-called antiphospholipid antibodies (aPL) as anticardiolipin antibodies (aCL) or lupus anticoagulant (LA). Minor alterations in the anticoagulation, infection, and surgical stress may trigger widespread thrombosis. The incidence of thrombosis is highest during the following perioperative periods: preoperatively during the withdrawal of warfarin, postoperatively during the period of hypercoagulability despite warfarin or heparin therapy, or postoperatively before adequate anticoagulation achievement. Cardiac valvular pathology includes irregular thickening of the valve leaflets due to deposition of immune complexes that may lead to vegetations and valve dysfunction; a significant risk factor for stroke. Patients with APLS are at increased risk for thrombosis and adequate anticoagulation is of vital importance during cardiopulmonary bypass (CPB). A successful outcome requires multidisciplinary management in order to prevent thrombotic or bleeding complications and to manage perioperative anticoagulation. More work and reporting on anticoagulation management and adjuvant therapy in patients with APLS during extracorporeal circulation are necessary.
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Platelet Activation and Anti-Phospholipid Antibodies Collaborate in the Activation of the Complement System on Platelets in Systemic Lupus Erythematosus
Lood, Christian
Tydén, Helena
Gullstrand, Birgitta
Sturfelt, Gunnar
Jönsen, Andreas
Truedsson, Lennart
Bengtsson, Anders A.
PLoS ONE
Anti-phospholipid (aPL) antibodies are important contributors to development of thrombosis in patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE). The underlying mechanism of aPL antibody-mediated thrombosis is not fully understood but existing data suggest that platelets and the complement system are key components. Complement activation on platelets is seen in SLE patients, especially in patients with aPL antibodies, and has been related to venous thrombosis and stroke. The aim of this study was to investigate if aPL antibodies could support classical pathway activation on platelets in vitro as well as in SLE patients. Furthermore, we investigated if complement deposition on platelets was associated with vascular events, either arterial or venous, when the data had been adjusted for traditional cardiovascular risk factors. Finally, we analyzed if platelet complement deposition, both C1q and C4d, was specific for SLE. We found that aPL antibodies supported C4d deposition on platelets in vitro as well as in SLE patients (p = 0.001 and p<0.05, respectively). Complement deposition on platelets was increased in SLE patients when compared with healthy individuals (p<0.0001). However, high levels of C4d deposition and a pronounced C1q deposition were also seen in patients with rheumatoid arthritis and systemic sclerosis. In SLE, C4d deposition on platelets was associated with platelet activation, complement consumption, disease activity and venous (OR = 5.3, p = 0.02), but not arterial, thrombosis, observations which were independent of traditional cardiovascular risk factors. In conclusion, several mechanisms operate in SLE to amplify platelet complement deposition, of which aPL antibodies and platelet activation were identified as important contributors in this investigation. Complement deposition on platelets was identified as a marker of venous, but not arterial thrombosis, in SLE patients independently of traditional risk factors and aPL antibodies. Further studies are needed to elucidate the role of complement deposition on platelets in development of venous thrombosis.
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Review on Effectiveness of Primary Prophylaxis in aPLs with and without Risk Factors for Thrombosis: Efficacy and Safety
Qushmaq, Nahid A.
Al-Emadi, Samar A.
ISRN Rheumatology
Context. Antiphospholipid antibodies syndrome is an autoimmune disorder that is characterized by the association between presence of antiphospholipid antibodies and risk of thrombosis and/or pregnancy morbidity. Objectives. To systematically review the evidence for primary prophylaxis in patients with antiphospholipids antibodies syndrome or APS with or without other traditional risk factors of thrombosis when they did not have any thrombotic event yet. Methods. PubMed, the Cochrane Library, and Allied Health Literature were searched for studies that examined the efficacy and safety of primary prophylaxis in aPL patients from 1990 to February 2013. We examined literature looking at patients with aPLs with other risk factors for thrombosis and aPLs with no additional risk factors for thrombosis. Conclusion. We concluded that, in patients with aPLs, primary prophylaxes with HCQ and aspirin have been observed to reduce the frequency of thrombotic events in the case of asymptomatic aPL-positive patients with SLE. We also in this study concluded that LDA was effective in patients with autoimmune diseases. Independent cardiovascular risk factors include autoimmune defects such as SLE, rheumatoid arthritis, and atherosclerosis, where overall venous thrombosis will be induced by systemic inflammation. This review concludes that HCQ is an effective primary approach when compared to aspirin.
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Association of Autoantibodies to Heat-Shock Protein 60 With Arterial Vascular Events in Patients With Antiphospholipid Antibodies
Dieudé, Mélanie
Correa, José A.
Neville, Carolyn
Pineau, Christian
Levine, Jerrold S.
Subang, Rebecca
Landolt-Marticorena, Carolina
Su, Jiandong
Kassis, Jeannine
Solymoss, Susan
Fortin, Paul R.
Rauch, Joyce
Arthritis and rheumatism
Anti–heat shock protein 60 autoantibodies (anti-Hsp60) are associated with cardiovascular disease and are known to affect endothelial cells in vitro, and we have recently shown that anti-Hsp60 promote thrombosis in a murine model of arterial injury. Based on those findings, we undertook the present study to investigate the hypothesis that the presence of anti-Hsp60, alone or in combination with other thrombogenic risk factors, is associated with an elevated risk of vascular events.
The study population was derived from 3 ongoing cohort studies: 2 independent systemic lupus erythematosus (SLE) registries and 1 cohort comprising SLE patients and non-SLE patients. Data from a total of 402 participants were captured; 199 of these participants had had confirmed vascular events (arterial vascular events in 102, venous vascular events in 76, and both arterial and venous vascular events in 21). Anti-Hsp60 were detected by enzyme-linked immunoassay, and association with vascular events was assessed by regression analysis.
Multiple regression analysis revealed that arterial vascular events were associated with male sex, age, and hypertension. Analyses of the vascular events according to their origin showed an association of anti-Hsp60 with arterial vascular events (odds ratio 2.26 [95% confidence interval 1.13–4.52]), but not with venous vascular events. Anti-Hsp60 increased the risk of arterial vascular events (odds ratio 5.54 [95% confidence interval 1.89–16.25]) in antiphospholipid antibody (aPL)–positive, but not aPL-negative, individuals.
We demonstrate that anti-Hsp60 are associated with an increased risk of arterial vascular events, but not venous vascular events, in aPL-positive individuals. These data suggest that anti-Hsp60 may serve as a useful biomarker to distinguish risk of arterial and venous vascular events in patients with aPL.
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Antiphospholipid antibodies in black south africans with hiv and acute coronary syndromes: prevalence and clinical correlates
Becker, Anthony C
Libhaber, Elena
Sliwa, Karen
Singh, Sham
Stewart, Simon
Tikly, Mohammed
Essop, Mohammed R
BMC Research Notes
HIV infection is associated with a high prevalence of antiphospholipid antibodies (aPL) and increased thrombotic events but the aetiopathogenic link between the two is unclear.
Prospective single centre study from Soweto, South Africa, comparing the prevalence of aPL in highly active anti-retroviral therapy (HAART) naïve HIV positive and negative patients presenting with Acute Coronary Syndromes (ACS). Between March 2004 and February 2008, 30 consecutive black South African HIV patients with ACS were compared to 30 black HIV negative patients with ACS. The HIV patients were younger (43 ± 7 vs. 54 ± 13, p = 0.004) and besides smoking (73% vs. 33%, p = 0.002) and lower HDL levels (0.8 ± 0.3 vs. 1.1 ± 0.4, p = 0.001) had fewer risk factors than the control group. HIV patients had a higher prevalence of anticardiolipin (aCL) IgG (47% vs. 10%, p = 0.003) and anti-prothrombin (aPT) IgG antibodies (87% vs. 21%, p < 0.001) but there was no difference in the prevalence of the antiphospholipid syndrome (44% vs. 24%, p = N/S) and aPL were not predictive of clinical or angiographic outcomes.
Treatment naïve black South African HIV patients with ACS are younger with fewer traditional coronary risk factors than HIV negative patients but have a higher prevalence and different expression of aPL which is likely to be an epiphenomenon of the HIV infection rather than causally linked to thrombosis and the pathogenesis of ACS.
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Antiphospholipid Antibodies and Multiple Organ Failure in Critically Ill Cancer Patients
Salluh, Jorge I. F.
Soares, Márcio
De Meis, Ernesto
Clinics (Sao Paulo, Brazil)
To describe the clinical outcomes and thrombotic events in a series of critically ill cancer patients positive for antiphospholipid (aPL) antibodies.
Retrospective case series study.
Medical-surgical oncologic intensive care unit (ICU).
Patients and Participants: Eighteen patients with SIRS/sepsis and multiple organ failure (MOF) and positive for aPL antibodies, included over a 10-month period.
aPL antibodies and coagulation parameters were measured up to 48 hours after the occurrence of acrocyanosis or arterial/venous thrombotic events. When current criteria for the diagnosis of aPL syndrome were applied, 16 patients met the criteria for "probable" and two patients had a definite diagnosis of APL syndrome in its catastrophic form (CAPS). Acrocyanosis, arterial events and venous thrombosis were present in eighteen, nine and five patients, respectively. Sepsis, cancer and major surgery were the main precipitating factors. All patients developed MOF during the ICU stay, with a hospital mortality rate of 72% (13/18). Five patients were discharged from the hospital. There were three survivors at 90 days of follow-up. New measurements of lupus anticoagulant (LAC) antibodies were performed in these three survivors and one patient still tested positive for these antibodies.
In this small series of patients, we observed a high frequency of auto-antibodies and micro- and macro-vascular thrombotic events in critically ill cancer patients. The coexistence of sepsis or SIRS and aPL antibodies was often associated with MOF and death. More studies are necessary to determine the pathophysiological significance of antiphospholipid antibodies in severely ill cancer patients.
Antiphospholipid syndrome; Multiple organ failure; Cancer; Thrombosis; Sepsis; Lupus anticoagulant
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Long-Term Survival in a Large Cohort of Patients with Venous Thrombosis: Incidence and Predictors
Flinterman, Linda E.
van Hylckama Vlieg, Astrid
Cannegieter, Suzanne C.
Rosendaal, Frits R.
PLoS Medicine
Linda Flinterman and colleagues report on the long-term mortality rate for individuals who have experienced a first venous thrombosis or pulmonary embolism. They describe an ongoing elevated risk of death for individuals who had experienced a venous thrombosis or pulmonary embolism as compared to controls, for up to eight years after the event.
Venous thrombosis is a common disease with a high mortality rate shortly after the event. However, details on long-term mortality in these patients are lacking. The aim of this study was to determine long-term mortality in a large cohort of patients with venous thrombosis.
Methods and Findings
4,947 patients from the Multiple Environmental and Genetic Assessment study of risk factors for venous thrombosis (MEGA study) with a first nonfatal venous thrombosis or pulmonary embolism and 6,154 control individuals without venous thrombosis, aged 18 to 70 years, were followed up for 8 years. Death and causes of death were retrieved from the Dutch death registration. Standardized mortality ratios (SMRs) were calculated for patients compared with control individuals. Several subgroups were studied as well.
736 participants (601 patients and 135 controls) died over a follow-up of 54,948 person-years. The overall mortality rate was 22.7 per 1,000 person-years (95% CI 21.0–24.6) for patients and 4.7 per 1,000 person-years (95% CI 4.0–5.6) for controls. Patients with venous thrombosis had a 4.0-fold (95% CI 3.7–4.3) increased risk of death compared with controls. The risk remained increased up to 8 years after the thrombotic event, even when no additional comorbidities were present. The highest risk of death was found for patients with additional malignancies (SMR 5.5, 95% CI 5.0–6.1). Main causes of death were diseases of the circulatory system, venous thrombosis, and malignancies. Main limitation was a maximum age of 70 at time of inclusion for the first event. Therefore results can not be generalized to those in the highest age categories.
Patients who experienced a first venous thrombosis had an increased risk of death which lasted up to 8 years after the event, even when no comorbidities were present at time of thrombosis. Future long-term clinical follow-up could be beneficial in these patients.
Please see later in the article for the Editors' Summary
Editors' Summary
The term venous thrombosis describes the clinical situation—more common during pregnancy, after surgery, or serious illness—in which a blood clot lodges in a vein. One specific type, which is more serious, involves the clot forming in a major vein in the lower leg and thigh and is termed a deep venous thrombosis. The clot can block blood flow and cause swelling and pain, but more seriously, can break off and move through the bloodstream, causing an embolism. An embolism can get stuck in the brain (and cause a stroke), lungs (and cause a pulmonary embolism), heart (to cause a heart attack), and/or other areas of the body, leading to severe damage.
Venous thrombosis is known to be associated with considerable short-term morbidity and mortality: the mortality rate after venous thrombosis is about 20% within one year and studies to date have suggested that the mortality rate is two to four times higher for patients with pulmonary embolism, of whom 10%–20% die within three months after the event. Many factors are associated with venous thrombosis, and the underlying cause of the thrombosis affects survival; for example, those with thrombotic events provoked by surgery or trauma have a lower mortality risk than patients with thrombosis caused by malignancy. Furthermore, about 10%–20% of patients who have had a venous thrombosis develop a recurrence within five years and up to 50% develop post-thrombotic syndrome—long-term swelling, pain, and changes in skin color.
Why Was This Study Done?
It is currently unknown whether the poor prognosis associated with venous thrombosis is limited to the months following the thrombotic event, or persists for years afterwards. So in this study, the researchers sought to answer this question by analyzing the long-term survival in a large cohort of patients who had experienced a first venous thrombosis and who were all followed for up to eight years.
What Did the Researchers Do and Find?
The researchers used the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study (MEGA study), which was a case-control study involving 4,965 consecutive patients aged 18 to 70 years who were objectively diagnosed with a deep venous thrombosis or pulmonary embolism and recruited from six anticoagulation clinics in the Netherlands between March 1999 and September 2004. The control group consisted of partners of patients (n = 3,297) and a random control group matched on age and sex (n = 3,000). The researchers obtained causes of death from the Central Bureau of Statistics and for the observation period (30 days after the venous thrombosis, to either death or end of follow-up between February 2007 and May 2009) compared cause-specific death rates of the patients to those of the general Dutch population. The researchers devised specialist survival models (called Kaplan-Meier life-tables) and calculated standardized mortality ratios (SMRs—the ratio of the observed number of deaths over the number of deaths expected) to estimate relative rates of all cause mortality by type of the initial thrombosis and the underlying cause.
Using these methods, the researchers found that the overall mortality rate in patients with thrombosis was substantially greater than in the control group (22.7 per 1,000 person-years compared to 4.7 per 1,000 person-years). Apart from malignancies, the researchers found that the main causes of death were diseases of the circulatory and respiratory system. Patients with venous thrombosis and malignancy had the highest risk of mortality: 55% died during follow-up. Patients with venous thrombosis without malignancy had an overall 2-fold increased risk of mortality compared to the control group and this risk was comparable for patients with different forms of thrombosis (such as deep venous thrombosis and pulmonary embolus). According to the researchers' calculations, the relative risk of death was highest during the first three years after thrombosis, but for those with thrombosis of unknown cause, the risk of death increased by two-fold up to eight years after the thrombosis. Furthermore, the researchers found that the highly increased risk of death for those with pulmonary embolism is mainly only for the first month as long-term survival is similar to that of patients with a deep venous thrombosis.
What Do These Findings Mean?
These findings show that patients who have experienced a venous thrombosis for the first time have an increased risk of death, which may last up to eight years after the event. These findings have important clinical implications and suggest that long-term clinical follow-up could be beneficial in patients who have experienced a venous thrombosis for the first time.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001155.
Wikipedia provides information about venous thrombosis note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Medline has patient-friendly information about deep venous thrombosis and pulmonary embolism
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Clinical Implications of Elevated Antiphospholipid Antibodies in Adult Patients with Primary Immune Thrombocytopenia
Yang, Young-Joon
Yun, Gak-Won
Song, Ik-Chan
Baek, Seung-Woo
Lee, Kyu-Seop
Ryu, Hye Won
Lee, Myung-Won
Lee, Hyo-Jin
Yun, Hwan-Jung
Kim, Samyong
Jo, Deog-Yeon
The Korean Journal of Internal Medicine
Antiphospholipid antibodies (aPL) have been detected in various proportions of patients with primary immune thrombocytopenia (ITP), but the clinical significance of this is debatable. The present study aimed to determine the frequency and clinical implications of elevated aPL in adult patients with ITP.
We prospectively studied newly diagnosed adult patients with ITP who were enrolled between January 2003 and December 2008 at Chungnam National University Hospital. They were evaluated for the presence of lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) at diagnosis and were followed for the development of thrombosis.
Seventy consecutive patients with ITP (median age, 48 years; range, 18 to 79) were enrolled. Twenty patients (28.5%) were positive for aPL at the time of diagnosis: aCL alone in 15 (75%), aCL and LA in two (10%), and LA alone in three (15%). Patients who had platelet counts < 50,000/µL were administered oral prednisolone with or without intravenous immune globulin. No difference was found between the aPL-positive and -negative groups regarding gender, initial platelet count, and response to the therapy. After a median follow-up of 20 months (range, 2 to 68), two of 20 patients who were aPL-positive (10%) developed thrombosis, whereas no thrombotic event was found among those who were aPL-negative.
Our data suggest that aPL levels should be determined at the initial presentation of ITP and that patients found to be aPL-positive should receive closer follow-up for thrombotic events.
Antibodies, anticardiolipin; Antiphospholipid syndrome; Purpura, thrombocytopenic, idiopathic; Lupus coagulation inhibitor; Thrombosis
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Factor V Leiden and Thrombosis in Patients with Systemic Lupus Erythematosus (SLE): A Meta-analysis
Kaiser, R.
Barton, J.L.
Chang, M.
Catanese, JJ.
Li, Y.
Begovich, A.B.
Criswell, LA.
Genes and immunity
To perform a meta-analysis of the association between the factor V Leiden polymorphism (FVL) and thrombosis among patients with SLE and/or antiphospholipid antibody (aPL) positivity. Included studies recruited patients based on SLE or aPL positive status, confirmed subjects' SLE diagnosis as defined by the American College of Rheumatology, and documented thrombotic events. Excluded studies were non-English or considered only arterial thrombosis. Individual patient data, available from five studies, together with unpublished data from 1210 European-American SLE patients from the UCSF Lupus Genetics Collection genotyped for FVL, were further analyzed. Seventeen studies (n=2090 subjects) were included in the initial meta-analysis. Unadjusted odds ratios (OR) were calculated to assess association of FVL with thrombosis. The OR for association of thrombosis with FVL was 2.88 (95% C.I. 1.98-4.20). In the secondary analysis with our individual patient dataset (n=1447 European-derived individuals), SLE subjects with the FVL polymorphism still had more than two times the odds of thrombosis compared to subjects without this polymorphism, even when adjusting for covariates such as gender, age, and aPL status. SLE and/or aPL positive patients with the FVL variant have more than two times the odds of thrombosis compared to those without this polymorphism.
Systemic lupus erythematosus; factor V Leiden polymorphism; thrombosis; risk factors; antiphospholipid antibodies
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Assessment of the 2006 revised antiphospholipid syndrome classification criteria
Kaul, Mala
Erkan, Doruk
Sammaritano, Lisa
Lockshin, Michael D
Annals of the Rheumatic Diseases
To analyse antiphospholipid (aPL) antibody‐positive patients using the 2006 revised antiphospholipid syndrome (APS) classification criteria.
A descriptive study of 200 aPL‐positive patients identified in a local, hospital‐based registry, analysing demographic, clinical and aPL characteristics. Patients were analysed for (1) fulfilment of the 1999 original (Sapporo) and 2006 revised APS classification criteria; (2) non‐criteria aPL features (for all aPL‐positive patients, based on the 2006 revised criteria definitions); and (3) non‐aPL thrombosis risk factors at the time of the clinical events (for patients with APS, based on the 2006 revised criteria stratifications).
Of the 200 patients, 183 patients had sufficient data for analysis. Of these, 39 (21%) patients did not meet the laboratory requirement of the original 1999 criteria. Of 81 patients with APS who met the 1999 classification criteria, 47 (58%) also met the 2006 revised criteria. Of 63 asymptomatic (no vascular or pregnancy events) aPL‐positive patients who met the laboratory requirement of the 1999 classification criteria, 38 (60%) also met the laboratory requirement of the 2006 revised criteria. More than 50% of the patients with APS with vascular events had identifiable non‐aPL thrombosis risk factors at the time of clinical events.
Only 59% of the patients meeting the 1999 APS Sapporo classification criteria met the 2006 APS classification criteria. The revised criteria will have positive implications in APS research by way of limiting the inclusion of a heterogeneous group of patients and also by way of providing a risk‐stratified approach.
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A Case Series of HIV-Seropositive Patients and Hypercoagulable State—Is It Difficult to Treat Even with Therapeutic Anticoagulation?
Sule, Ashish Anil
Pandit, Nihar
Handa, Pankaj
Chadachan, Veerandra
Tan, Endean
Sum, Faith Nadine Choo Yun
Joyce, Er Hui Ling
Chin, Tay Jam
The International Journal of Angiology : Official Publication of the International College of Angiology, Inc
Patients with human immunodeficiency virus (HIV) are at risk of developing thrombosis and are 8 to 10 times more likely to develop thrombosis than the general population. Moreover, if they have hypercoagulable state they can have severe thrombosis and life-threatening thrombotic events. The purpose of this retrospective study is to analyze hypercoagulable state in HIV-seropositive patients who have been diagnosed with venous thromboembolism (VTE). This study is a subgroup study of a larger cohort group of HIV-seropositive patients with VTE followed up with our vascular medicine outpatient clinic. The patients included for this study were HIV-seropositive patients with hypercoagulable state, analyzed over the past 3 years, and followed prospectively. HIV-seropositive patients with arterial thrombosis were excluded. These patients had minimum, regular follow-up of 3 months, with a Doppler scan in the beginning and last follow-up. All the patients were analyzed for hypercoagulable state and the patients selected in this study were those who were tested positive for hypercoagulable state. All patients were analyzed for age, gender, race, site of thrombosis, coagulation factors, lipid panel, type of antiretroviral treatment, past or present history of infections or malignancy, CD4 absolute and helper cell counts at the beginning of thrombosis, and response to treatment and outcome. Patients with HIV with arterial thrombosis were excluded. The study was approved by the ethics committee. Five patients were included in this study. The mean age was 47.8 years (range 38 to 58 years). All were male patients with lower limb thrombosis. Most common venous thrombosis was popliteal vein thrombosis, followed by common femoral, superficial femoral, and external iliac thrombosis. Two patients had deficiency of protein S, two had high homocysteine levels, one had deficiency of antithrombin 3, and one had increase in anticardiolipin immunoglobulin G antibody. All the patients were taking nucleoside and nonnucleoside inhibitors but only one patient was taking protease inhibitors. There was no history of malignancy but two patients had past history of tuberculosis. The mean absolute CD4 counts were 244 cells/UL (range 103 to 392 cells/UL) and helper CD4 counts were 19.6 cells/UL (range 15 to 30 cells/UL). All were anticoagulated with warfarin or enoxaparin. There was complete resolution of deep vein thrombosis only in one patient on long-term anticoagulation but there was no resolution of thrombosis in the other four patients despite of therapeutic anticoagulation for more than 6 months. All the patients are alive and on regular follow-up. Thrombosis in HIV patients is seen more commonly in middle aged, community ambulant male patients. The most common hypercoagulable state was noted as deficiency of protein S and hyperhomocysteinemia. Eighty percent of the patients did not respond to therapeutic anticoagulation.
deep vein thrombosis; duplex; DVT; enoxaparin; factor V Leiden; low molecular weight heparin; proximal
Related Articles
Synergistic Effects of Hypofibrinolysis and Genetic and Acquired Risk Factors on the Risk of a First Venous Thrombosis
Meltzer, Mirjam E
Lisman, Ton
Doggen, Carine J. M
de Groot, Philip G
Rosendaal, Frits R
PLoS Medicine
Previously, we demonstrated that hypofibrinolysis, a decreased capacity to dissolve a blood clot as measured with an overall clot lysis assay, increases the risk of venous thrombosis. Here, we investigated the combined effect of hypofibrinolysis with established risk factors associated with hypercoagulability.
Methods and Findings
Fibrinolytic potential was determined with a plasma-based clot lysis assay in 2,090 patients with venous thrombosis and 2,564 control participants between 18 and 70 y of age enrolled in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based case-control study on venous thrombosis. Participants completed a standardized questionnaire on acquired risk factors.
Hypofibrinolysis alone, i.e., clot lysis time (CLT) in the fourth quartile (longest CLT) (in absence of the other risk factor of interest) increased thrombosis risk about 2-fold relative to individuals with CLT in the first quartile (shortest CLT). Oral contraceptive use in women with CLT in the first quartile gave an odds ratio (OR) of 2.6 (95% confidence interval [CI] 1.6 to 4.0), while women with hypofibrinolysis who used oral contraceptives had an over 20-fold increased risk of venous thrombosis (OR 21.8, 95% CI 10.2 to 46.7). For immobilization alone the OR was 4.3 (95% CI 3.2 to 5.8) and immobilization with hypofibrinolysis increased the risk 10.3-fold (95% CI 7.7 to 13.8). Factor V Leiden alone increased the risk 3.5-fold (95% CI 2.3 to 5.5), and hypofibrinolysis in factor V Leiden carriers gave an OR of 8.1 (95% CI 5.3 to 12.3). The combination of hypofibrinolysis and the prothrombin 20210A mutation did not synergistically increase the risk. All ORs and 95% CIs presented are relative to individuals with CLT in the first quartile and without the other risk factor of interest.
The combination of hypofibrinolysis with oral contraceptive use, immobilization, or factor V Leiden results in a risk of venous thrombosis that exceeds the sum of the individual risks.
Frits Rosendaal and colleagues show that the combination of hypofibrinolysis with oral contraceptive use, immobilization, or factor V Leiden results in a risk of venous thrombosis that exceeds the sum of the individual risks.
Editors' Summary
When a blood vessel is injured, proteins in the blood called clotting factors "coagulate" (solidify) the blood at the injury site. The resultant clot (thrombus) plugs the wound and prevents blood loss. When the injury has healed, other proteins dissolve the clot, a process called "fibrinolysis." Sometimes, however, a thrombus develops inside an undamaged blood vessel and partly or completely blocks the blood flow. A clot that occurs in one of the veins (vessels that take the blood to the heart) deep within the body (usually in the leg) is a deep vein thrombosis (DVT). Some DVTs have no symptoms; others cause pain, swelling, and tenderness in one leg. They are usually treated with heparin and warfarin, anticoagulant drugs that stop the clot growing. If left untreated, part of the clot (an embolus) can break off and travel to the lungs, where it can cause a life-threatening condition called a pulmonary embolism (PE).
Why Was This Study Done?
Most people are very unlikely to develop venous thrombosis (the collective term for DVT and PE), but anything that makes blood "hypercoagulable" (prone to clotting) increases this risk. Genetic risk factors can be inherited changes in blood clotting proteins (for example, a mutation in a gene coding for one protein, factor V, which is involved in clotting, is known as factor V Leiden—Leiden, The Netherlands, was where it was first described). There are also acquired risk factors such as taking oral contraceptives or being immobilized (for example, during bed rest). These risk factors often act in such a way that the risk of developing venous thrombosis for a person with multiple risk factors is greater than the sum of the individual risks. Another recently identified but little studied risk factor for venous thrombosis is "hypofibrinolysis," a decreased capacity to dissolve blood clots. In this study (part of the "MEGA" study on risk factors for venous thrombosis), the researchers investigate the combined effect of hypofibrinolysis and established risk factors associated with hypercoagulability on the risk of developing venous thrombosis.
What Did the Researchers Do and Find?
The researchers collected blood from more than 2,000 individuals after their first DVT or PE and from a similar number of persons without venous thrombosis (controls). For each blood sample, they measured the time it took to dissolve a clot generated from that blood in a test tube (the clot lysis time or CLT) and determined which participants had the factor V Leiden mutation or a genetic change in the clotting factor prothrombin that also increases blood coagulability. The study participants also completed a questionnaire about acquired risk factors for venous thrombosis. The researchers divided the participants into four equal-sized groups (quartiles) based on their CLT and used the quartile with the lowest CLT as the reference group for their statistical analyses; hypofibrinolysis was defined as a CLT in the highest quartile (the longest times). Participants with hypofibrinolysis alone were twice as likely to develop venous thrombosis as those with a CLT in the lowest quartile (the shortest times). Oral contraceptive use alone increased the risk of venous thrombosis 2.5-fold, whereas the combination of oral contraceptive use and hypofibrinolysis increased the risk 20-fold. The researchers also found synergistic effects on thrombosis risk for hypofibrinolysis combined with immobilization or with the factor V Leiden mutation but not with the prothrombin mutation.
What Do These Findings Mean?
These findings confirm that persons with hypofibrinolysis and hence longer CLTs have a greater risk of developing venous thrombosis than those with short CLTs. Because CLTs were measured after venous thrombosis had occurred, hypofibrinolysis could be an effect rather than a cause of this condition. However, this is unlikely because there was no association between how long after the venous thrombosis the blood sample was taken and the measured CLT. These findings also show that the combination of hypofibrinolysis with immobilization, the factor V Leiden mutation, and oral contraceptive use greatly increases the risk of venous thrombosis. This new information about the risk factors for venous thrombosis should help physicians to advise patients about reducing their chances of developing this life-threatening condition.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050097.
The MedlinePlus encyclopedia has pages on blood clots, deep vein thrombosis, and pulmonary embolism (in English and Spanish)
The US National Heart Lung and Blood Institute provides information on deep vein thrombosis, including an animation about how DVT causes pulmonary embolisms
The UK National Health Service Direct health encyclopedia provides information for patients on deep vein thrombosis (in several languages)
More information about the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) study is available on the Leiden University Medical Center Web site
Wikipedia has pages on coagulation and on fibrinolysis (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Related Articles
Antiphospholipid Antibodies Predict Progression of Abdominal Aortic Aneurysms
Duftner, Christina
Seiler, Rüdiger
Dejaco, Christian
Chemelli-Steingruber, Iris
Schennach, Harald
Klotz, Werner
Rieger, Michael
Herold, Manfred
Falkensammer, Jürgen
Fraedrich, Gustav
Schirmer, Michael
PLoS ONE
Antiphospholipid antibodies (aPLs) frequently occur in autoimmune and cardiovascular diseases and correlate with a worse clinical outcome. In the present study, we evaluated the association between antiphospholipid antibodies (aPLs), markers of inflammation, disease progression and the presence of an intra-aneurysmal thrombus in abdominal aortic aneurysm (AAA) patients.
APLs ELISAs were performed in frozen serum samples of 96 consecutive AAA patients and 48 healthy controls yielding positive test results in 13 patients (13.5%) and 3 controls (6.3%; n.s.). Nine of the 13 aPL-positive AAA patients underwent a second antibody testing >12 weeks apart revealing a positive result in 6 cases. APL-positive patients had increased levels of inflammatory markers compared to aPL-negative patients. Disease progression was defined as an increase of the AAA diameter >0.5 cm/year measured by sonography. Follow-up was performed in 69 patients identifying 41 (59.4%) patients with progressive disease. Performing multipredictor logistic regression analysis adjusting for classical AAA risk factors as confounders, the presence of aPLs at baseline revealed an odds ratio of 9.4 (95% CI 1.0–86.8, p = 0.049) to predict AAA progression. Fifty-five patients underwent a computed tomography in addition to ultrasound assessment indicating intra-aneurysmal thrombus formation in 82.3%. Median thrombus volume was 46.7 cm3 (1.9–377.5). AAA diameter correlated with the size of the intra-aneurysmal thrombus (corrcoeff = 0.721, p<0.001), however neither the presence nor the size of the intra-aneurysmal thrombus were related to the presence of aPLs.
In conclusion, the presence of aPLs is associated with elevated levels of inflammatory markers and is an independent predictor of progressive disease in AAA patients.
Related Articles
The dual role of innate immunity in the antiphospholipid syndrome
Rauch, J
Dieudé, M
Subang, R
Levine, JS
The antiphospholipid syndrome (APS), as both a primary syndrome and a syndrome in association with systemic lupus erythematosus (SLE), can be a devastating disease. It is unclear what factors (genetic and/or environmental) lead to the generation of antiphospholipid antibodies (aPL). It is equally unclear why only certain individuals with aPL develop clinical events. We hypothesize that innate immune activation plays a critical role at two distinct stages of APS, namely, the initiation phase, in which aPL first appear, and the effector phase, in which aPL precipitate a thrombotic event. According to the model we propose, aPL alone are insufficient to cause thrombosis and a concomitant trigger of innate immunity, e.g. a toll-like receptor (TLR) ligand, must be present for thrombosis to occur. Here, we discuss our findings that mice immunized with β2-glycoprotein I (β2GPI) and lipopolysaccharide (LPS), a TLR ligand, produce high levels of aPL and other SLE-associated autoantibodies, and develop lupus-like glomerulonephritis. We also discuss our data showing that autoantibodies to heat shock protein 60 (HSP60), an 'endogenous TLR ligand', promote thrombus generation in a murine model of arterial injury. Thus, both pathogen-derived TLR ligands (e.g. LPS) and endogenous TLR ligands (e.g. HSP60) may contribute to the pathogenesis of APS. This putative dual role of innate immunity provides new insight into the generation of aPL as well as the enigma of why some individuals with aPL develop APS, while others do not.
antiphospholipid syndrome; β2-glycoprotein I; heat shock protein 60; innate immunity; lipopolysaccharide; toll-like receptor ligands
Related Articles
Serum complement activation on heterologous platelets is associated with arterial thrombosis in patients with systemic lupus erythematosus and antiphospholipid antibodies
Peerschke, EIB
Yin, W
Alpert, DR
Roubey, RAS
Salmon, JE
Ghebrehiwet, B
Complement plays a major role in inflammation and thrombosis associated with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). A cross-sectional retrospective analysis was performed to evaluate serum complement fixation on platelets and thrombotic incidence using banked sera and clinical data from patients with SLE (n = 91), SLE with antiphospholipid antibodies (aPL) or APS (n = 78) and primary aPL (n = 57) or APS (n = 96). In-situ complement fixation was measured as C1q and C4d deposition on heterologous platelets using an enzyme-linked immunosorbent assay approach. Platelet activation by patient serum in the fluid phase was assessed via serotonin release assay. Enhanced in-situ complement fixation was associated with the presence of IgG aPL and IgG anti-β2 glycoprotein 1 antibodies (P < 0.05) and increased platelet activation (P < 0.005). Moreover, enhanced complement fixation, especially C4d deposition on heterologous platelets, was positively associated with arterial thrombotic events in patients with SLE and aPL (P = 0.039). Sera from patients with aPL possess an enhanced capacity for in-situ complement fixation on platelets. This capacity may influence arterial thrombosis risk in patients with SLE.
antiphospholipid syndrome; systemic lupus erythematosus; thrombosis
Related Articles
The persistence of anticardiolipin antibodies is associated with an increased risk of the presence of lupus anticoagulant and anti-β2-glycoprotein I antibodies
Neville, C.
Rauch, J.
Kassis, J.
Solymoss, S.
Joseph, L.
Belisle, P.
Subang, R.
Chang, E. R.
Fortin, P. R.
Rheumatology (Oxford, England)
We studied antiphospholipid antibodies (aPL) in blood samples from a cohort of individuals followed for thrombosis to determine whether the persistent presence of anticardiolipin antibodies (aCL) is associated with a greater likelihood of having lupus anticoagulant and/or anti-β2-glycoprotein I antibodies (LA/aβ2GPI).
Blood samples from 353 individuals who had been tested for aCL on at least two occasions were tested for aβ2GPI and LA. Two groups were defined: aCL-persistent, who tested aCL-positive on at least two occasions, and aCL non-persistent, who tested aCL-positive on fewer than two occasions. Multivariate logistic regressions were performed using LA/aβ2GPI, LA and aβ2GPI as outcome variables and the percentage of aCL-positive tests as the predictor variable, adjusted for age, gender, family history of cardiovascular disease (CVD), systemic lupus erythematosus (SLE), smoking and number of venous (VT) and arterial thromboses (AT).
Sixty-eight (19%) individuals were aCL persistent and 285 (81%) were aCL non-persistent. LA/aβ2GPI was found in 36 (53%) of the aCL persistent group and 38 (13%) of the aCL non-persistent group. The two groups were similar for age, gender and smoking. Family history of CVD, SLE, VT and AT were more frequent in the aCL persistent group. Multivariate analyses revealed that odds ratios for LA/aβ2GPI, LA and aβ2GPI were 1.34 [95% confidence interval (CI)=1.22–1.47], 1.36 (95% CI=1.24–1.50) and 1.47 (95% CI=1.31–1.65) respectively for each 10% increase in aCL-positive tests vs 0% positive tests.
Persistence of aCL positivity is associated with an increased risk of LA/aβ2GPI.
Antiphospholipid antibodies; Anticardiolipin antibodies; Lupus anticoagulant; Anti-β2-glycoprotein I antibodies
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U.K.'s Burt Calls for Probe of Sri Lanka War Crimes Allegations
June 15 (Bloomberg) -- U.K. Foreign Office Minister Alistair Burt urged Sri Lanka to initiate an "independent, thorough and credible investigation" into allegations that war crimes were committed during the conflict in the country that ended in May 2009, the Foreign and Commonwealth Office said in an e-mailed statement.
Burt commented after watching a Channel 4 television documentary titled "Sri Lanka's Killing Fields," about which he said he was "shocked by the horrific scenes," the statement said.
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Kenmore Intuition 31040 Vacuum
At 23 pounds, we found the Kenmore Intuition 31040 to be bulky, heavy, and difficult to maneuver. Its girth did help to make it stable, however, and it did not tip in any direction. It was great at picking up pet hair and embedded dirt from carpets, but performed poorly at cleaning up debris from bare floors. The quiet motor was also a plus. kenmore.com.
Type: Upright vacuum
Manufacturer's warranty: Limited to one year.
Reviewed: September 2010
Price When Reviewed: $249.99
- Great pet-hair and embedded-dirt removal
- Did not tip in any direction
- Very quiet motor
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- Bulky, heavy, and very hard to maneuver
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Krups 4-Slice Belgian Waffle Maker #F654-75
Although the Krups wasn't able to produce crisp waffles from a mix, it made nicely crisp waffles from scratch and was the most consistent...
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Nepali Woven Beaded Bracelet
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Jubilant color drenches this charmer from Nepal. Tiny multicolored glass beads are woven on soft cotton thread to create a beautiful and comfortable work of art. Wear one -- or three or four -- for the best-dressed wrist in town!
- Black Dot, Black Multi, Blue Multi, Brown Multi, Red, Purple, Dark Green, Independence Red, Light Lavender, Black, Clear Blue, Clear Silver, Pink Multi, Purple Multi, Red Multi, Pink Flower, Stripe, Green Multi, or White Dot
- 7" around (17.8 cm)
- Handmade in and fairly traded from Nepal
These traditional Nepalese beaded bracelets are handmade by a women's beading cooperative in Nepal, where women have been weaving with beads for centuries. Their highly-skilled work provides them with needed income, assisting them toward self-sufficiency and independence.
Created to help women worldwide gain economic security for themselves and their families by earning fair wages for their handiwork, Global Girlfriend sources women-made, fair-trade imported, eco-friendly products. By supporting long-term partnerships with the artisans, it fosters equal employment opportunities, healthy and safe working conditions, technical assistance, and development strategies to help reduce poverty, one community at a time. Become a "Global Girlfriend" and help build a brighter future for girlfriends around the globe!
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Carabelas Apartments
from £20 /night help Price for guests, Nights approx:
2 reviews
from £20 /night help Price for guests, Nights approx:
Estimated nightly price based on a weekly stay. Contact the advertiser to confirm the total cost.
Apartment / 2 bedrooms / sleeps 6
Availability Your dates are available
Apartment / 2 bedrooms / sleeps 6
|Key Info
Air conditioned holiday apartment less than one minute from the Levante beach. Very centrally situated with all the local amenities on its doorstep but set in quiet, pleasant gardens with private gated entrances.
Fully equipped holiday apartment with incredible views over the Levante promenade and beach.
|Sleeps up to 6, 2 bedrooms
|Check in time:
|Check out time:
|Nearest beach
|Levante 10 m
|Will consider
|Long term lets (over 1 month)
|Car not necessary
|Nearest travel links
|Nearest airport: Alicante 45 km, Nearest railway: Benidorm 3 km
|Family friendly
|Great for children of all ages
|Some pets are welcome - please contact the owner, No smoking at this property
Features and Facilities
|Sea view
|Shared outdoor pool (unheated)
|Air conditioning, TV, Satellite TV
|Kettle, Toaster, Iron
|Cooker, Microwave, Fridge, Freezer, Washing machine
|2 bedrooms, 1 bathrooms of which 1 Family bathrooms
|1 Sofa beds, Single beds (4), Dining seats for 6, Lounge seats for 4
|Linen provided, Towels provided
|Shared outdoor pool (unheated), Shared garden
|Secure parking, Suitable for people with restricted mobility, Wheelchair users
|Further details indoors
The balcony has been glazed-in to capture the winter sun but the glass slides back like patio doors for sunbathing.
|Further details outdoors
Secure parking available. A returnable deposit of 10 euros is required for the key.
The Valenciana region
Arguably the most famous coast in Spain, Costa Blanca draws millions of tourists each year.
Lying on the eastern coast, the White Coast is one of those resorts where everyone can find their place under the sun, from sophisticated towns where life goes on 25 hours a day to quaint little villages where the peace and tranquillity is feature.
Its clear blue waters and miles of white sandy beaches are certainly a major attraction.
Beautiful mountains parallel to the sea are on the north coast. Here you can marvel at the Moorish villages where olive trees and hidden coves abound.
To the south is where you will find the beaches mushrooming with palm trees, the sparkling, turquoise sea and rows of cafes and restaurants.
Benidorm is many things, but first and foremost it is a Mediterranean resort city on the stunningly beautiful Costa Blanca.
One of the initial attractions of Benidorm is its location, on the Mediterranean coast, opposite a beautiful bay which is split into two by the rocky tip of the old castle, and facing south. All the other sides are protected by mountain ranges, so the micro-climate, especially in Spring, Winter or Autumn, is very mild with considerably higher temperatures than along the rest of the coast.
As it has grown, Benidorm has added to its impressive infra-structure as a leisure resort and now offers its visitors infinite possibilities of entertainment for all ages.
Levante beach is the more popular and sort after and buzzing of the two beaches in Benidorm. It transmits a very happy and full of life sensation which encapsulates every visitor.
There are many activities such as a large theme park the Terra Mitica , the water park Aqualandia, etc, as well as many one day tours and other surrounding attractions.
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You're booking with
Angela Zandieh (Property Manager Zand Property Rental Service)
- 3 Years listed
5% Response rate
Calendar last updated:01 Jul 2015
Based in Spain
- English
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Payment accepted
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- Landline
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Minnesota's unemployment rate fell two-tenths of a percent in November to 4.6%. State labor analyst Steve Hine says seasonally-adjusted nonfarm employment fell by 800 jobs, but that small decline was offset by an upward revision of October's level by 1,000 jobs. In addition to that, numbers for the private sector in October were also revised upward, bringing the net gain over two months to nearly five thousand jobs. Hine says government lost 3,200 jobs in November while information led all sectors with 1,300 jobs gained. The US jobless rate was 7% last month.
November Unemployment Numbers