Thrombosis The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Advances in Medical Revascularisation Treatments in Acute Ischemic Stroke Tue, 30 Dec 2014 12:43:23 +0000 Urgent reperfusion of the ischaemic brain is the aim of stroke treatment and there has been ongoing research to find a drug that can promote vessel recanalisation more completely and with less side effects. In this review article, the major studies which have validated the use and safety of tPA are discussed. The safety and efficacy of other thrombolytic and anticoagulative agents such as tenecteplase, desmoteplase, ancrod, tirofiban, abciximab, eptifibatide, and argatroban are also reviewed. Tenecteplase and desmoteplase are both plasminogen activators with higher fibrin affinity and longer half-life compared to alteplase. They have shown greater reperfusion rates and improved functional outcomes in preliminary studies. Argatroban is a direct thrombin inhibitor used as an adjunct to intravenous tPA and showed higher rates of complete recanalisation in the ARTTS study with further studies which are now ongoing. Adjuvant thrombolysis techniques using transcranial ultrasound are also being investigated and have shown higher rates of complete recanalisation, for example, in the CLOTBUST study. Overall, development in medical therapies for stroke is important due to the ease of administration compared to endovascular treatments, and the new treatments such as tenecteplase, desmoteplase, and adjuvant sonothrombolysis are showing promising results and await further large-scale clinical trials. H. Asadi, B. Yan, R. Dowling, S. Wong, and P. Mitchell Copyright © 2014 H. Asadi et al. All rights reserved. New Thrombotic Events in Ischemic Stroke Patients with Elevated Factor VIII Wed, 17 Dec 2014 00:10:04 +0000 Background. Heightened levels of Factor VIII (FVIII) have been associated with both arterial and venous thrombosis. While elevated FVIII is common during acute ischemic stroke (AIS), whether elevated FVIII confers an increased risk for recurrent thrombotic events (RTEs) following AIS has not been previously explored. Methods. Consecutive AIS patients who presented to our center between July 2008 and September 2013 and had FVIII measured during admission were identified from our stroke registry. Baseline characteristics and the occurrence of RTE (recurrent or progressive ischemic stroke, DVT/PE, and MI) were compared in patients with and without elevated FVIII levels. Results. Of the 298 patients included, 203 (68.1%) had elevated FVIII levels. Patients with elevated FVIII had higher rates of any in-hospital RTE (18.7% versus 8.4%, ). This association remained after adjustment for baseline stroke severity and etiology (OR 1.01, 95% CI 1.00–1.01, ). Rates of major disability were also higher in patients who experienced a RTE (17.8% versus 3.2%, ). Conclusion. A significantly higher frequency of in-hospital RTEs occurred in AIS patients with elevated FVIII. The occurrence of such events was associated with higher morbidity. Further study is indicated to evaluate whether FVIII is a candidate biomarker for increased risk of RTEs following AIS. Brittany M. Gouse, Amelia K. Boehme, Dominique J. Monlezun, James E. Siegler, Alex J. George, Katherine Brag, Karen C. Albright, T. Mark Beasley, Cindy Leissinger, Ramy El Khoury, and Sheryl Martin-Schild Copyright © 2014 Brittany M. Gouse et al. All rights reserved. Variability in the Management of Superficial Venous Thrombophlebitis across Practitioners Based in North America and the Global Community Sun, 12 Oct 2014 00:00:00 +0000 Introduction. This study aimed to compare management patterns of patients with SVT among healthcare practitioners based in North America versus those in the global community. Methods. A 17-question, multiple choice survey with questions regarding SVT diagnosis and management strategies was provided to practitioners who attended the American Venous Forum (AVF) meeting in 2011. Results. There were 487 practitioners surveyed with 365 classified as North American (US or Canada) and 122 (56 Europe, 25 Asia, 11 South America, and 7 Africa) representing the global community. The key difference seen between the groups was in the initial imaging study used in patients presenting with SVT () and physicians in the US ordered fewer bilateral duplex ultrasounds and more unilateral duplex ultrasounds (49.6% versus 58.2%, 39.7% versus 34.4%). In the US cohort, phlebologists and vascular surgeons constituted 82% () of the specialties surveyed. In the global community, SVT was managed by phlebologists or vascular surgeons 44% () of the time. Surgical management was highly variable between groups. Conclusion. There is currently no consensus between or among practitioners in North America or globally as to the surgical management of SVT, duration of follow-up, and anticoagulation parameters. Anahita Dua, Jennifer A. Heller, Bhavin Patel, and Sapan S. Desai Copyright © 2014 Anahita Dua et al. All rights reserved. Cardioembolic Sources in Stroke Patients in South of Brazil Thu, 02 Oct 2014 00:00:00 +0000 Background. Stroke is a leading cause of mortality and disability in Brazil and around the world. Cardioembolism is responsible for nearly 30% of the origins of ischemic stroke. Methods. We analyzed data of 256 patients with cardioembolic ischemic stroke (according to TOAST classification) who were admitted into the Hospital São Lucas-PUCRS from October 2011 to January 2014. The cardioembolic subtype was divided into six subgroups: arrhythmias, valvular heart disease, coronary artery disease, cardiomyopathy, septal abnormalities, and intracardiac injuries. The prevalence of the most important cardiovascular risk factors and medications in use for prevention of systemic embolism by the time of hospital admission was analyzed in each patient. Results. Among 256 patients aged 60.2 +/− 6.9 years, 132 males, arrhythmias were the most common cause of cardioembolism corresponding to 50.7%, followed by valvular heart disease (17.5%) and coronary artery disease (16%). Hypertension (61.7%) and dyslipidemia (43.7%) were the most common risk factors. Less than 50% of patients with arrhythmias were using oral anticoagulants. Conclusions. Identifying the prevalence of cardioembolic stroke sources subgroups has become an increasingly important role since the introduction of new oral anticoagulants. In this study, arrhythmias (especially atrial fibrillation) were the main cause of cardioembolism. Luiz Carlos Porcello Marrone, João Pedro Farina Brunelli, Ricardo Lutzky Saute, Gustavo Henrique Tomasi, Bianca Cecchele Madeira, William Alves Martins, Robson Dupont Rohr, Ana Paula Heck, Luiz Ricardo Botton, Marilia Martins de Castro, Rodrigo Bodanese, Luiz Carlos Bodanese, Antônio Carlos Huf Marrone, and Jaderson Costa da Costa Copyright © 2014 Luiz Carlos Porcello Marrone et al. All rights reserved. Study of Associated Genetic Variants in Indian Subjects Reveals the Basis of Ethnicity Related Differences in Susceptibility to Venous Thromboembolism Tue, 30 Sep 2014 00:00:00 +0000 The genetic variants linked with the susceptibility of individuals to VTE are well known; however, the studies explaining the ethnicity based difference in susceptibility to VTE are limited. Present study assesses mutations in six candidate genes contributing to the etiology of VTE in Indian subjects. The study comprised 93 VTE patients and 102 healthy controls. A PCR-RFLP based analysis was performed for nine mutations in the following genes associated with VTE: favtor V Leiden (FVL), prothrombin, tissue factor pathway inhibitor (TFPI), fibrinogen-beta, plasminogen activator inhibitor 1 (PAI-1), and methylene tetrahydrofolatereductase (MTHFR). All the subjects were found to be monomorphic for FVL 1691G/A, prothrombin 20210G/A and TFPI −536C/T mutations. The mutation in the MTHFR gene (677C/T) was observed only in patients. Contrarily, higher frequency of mutation in the PAI-1 −844G/A and the fibrinogen-β −455G/A was observed in controls in comparison to the patients. This study suggests that the PAI-1 −844G/A and fibrinogen-β −455G/A could be protective variants against VTE in Indians. While MTHFR 677C/T mutation was found to be associated, in contrast to other populations, the established genetic variants FVL 1691G/A, prothrombin 20210G/A, and TFPI −536C/T may not be associated with VTE in Indians thus revealing the basis of ethnicity related differences in susceptibility of Indians to VTE. Babita Kumari, Swati Srivastava, Tathagat Chatterjee, Rig Vardhan, Tarun Tyagi, Neha Gupta, Anita Sahu, Khem Chandra, and Mohammad Zahid Ashraf Copyright © 2014 Babita Kumari et al. All rights reserved. Thromboembolism Prevention via Transcatheter Left Atrial Appendage Closure with Transeosophageal Echocardiography Guidance Tue, 11 Feb 2014 12:12:57 +0000 Atrial fibrillation (AF) is an independent risk factor for stroke. Anticoagulation therapy has a risk of intracerebral hemorrhage. The use of percutaneous left atrial appendage (LAA) closure devices is an alternative to anticoagulation therapy. Echocardiography has a leading role in LAA closure procedure in patient selection, during the procedure and during followup. A comprehensive echocardiography study is necessary preprocedural in order to identify all the lobes of the LAA, evaluate the size of the LAA ostium, look for thrombus or spontaneous echo contrast, and evaluate atrial anatomy, including atrial septal defect and patent foramen ovale. Echocardiography is used to identify potential cardiac sources of embolism, such as atrial septal aneurysm, mitral valve disease, and aortic debris. During the LAA occlusion procedure transeosophageal echocardiography provides guidance for the transeptal puncture and monitoring during the release of the closure device. Procedure-related complications can be evaluated and acceptable device release criteria such as proper position and seating of the occluder in the LAA, compression, and stability can be assessed. Postprocedural echocardiography is used for followup to assess the closure of the LAA ostium. This overview paper describes the emerging role of LAA occlusion procedure with transeosophageal echocardiography guidance as an alternative to anticoagulation therapy in patients with AF. John Palios and Ioannis Paraskevaidis Copyright © 2014 John Palios and Ioannis Paraskevaidis. All rights reserved. Elevated Heparin-Induced Antibodies Are More Common in Diabetic Patients with Vascular Disease Thu, 06 Feb 2014 00:00:00 +0000 Background. Hypercoagulable disorders can lead to deep vein thrombosis (DVT), arterial thrombosis or embolization, and early or recurrent bypass graft failure. The purpose of this study was to identify whether diabetes increased the likelihood of heparin-induced platelet factor 4 antibodies in at risk vascular patients. Methods. We reviewed clinical data on 300 consecutive patients. A hypercoagulable workup was performed if patients presented with (1) early bypass/graft thrombosis (<30 days), (2) multiple bypass/graft thrombosis, and (3) a history of DVT, pulmonary embolus (PE), or native vessel thrombosis. Relevant clinical variables were analyzed and compared between patients with diabetes (DM) and without diabetes (nDM). Results. 85 patients (47 women; age 53 16 years, range 16–82 years) had one of the defined conditions and underwent a hypercoagulable evaluation. Screening was done in 4.7% of patients with early bypass graft thrombosis, 60% of patients were screened because of multiple bypass or graft thrombosis, and 35.3% had a previous history of DVT, PE, or native vessel thrombosis. Of the 43 patients with DM and 42 nDM evaluated, 59 patients (69%) had an abnormal hypercoagulable profile. An elevated heparin antibody level was present in 30% of DM and 12% of nDM patients (chi-squared test ). Additionally, DM was associated with a higher likelihood of arterial complications while nDM was associated with a higher rate of venous adverse events (chi-squared test ). Conclusions. Diabetes is associated with a higher likelihood of developing heparin-induced antibodies and an increased combined incidence of arterial complications that include early or multiple bypass/graft thrombosis. This finding may influence the choice of anticoagulation in diabetic patients at risk with vascular disease. Joseph J. Naoum, Nibal R. Chamoun, Mitul S. Patel, Tiffany K. Street, Mazen Haydar, Jean Bismuth, Hosam F. El-Sayed, Mark G. Davies, Alan B. Lumsden, and Eric K. Peden Copyright © 2014 Joseph J. Naoum et al. All rights reserved. Dabigatran, Rivaroxaban, or Apixaban versus Warfarin in Patients with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Subgroups Sun, 22 Dec 2013 15:52:15 +0000 Background. New oral anticoagulants (NOAC; rivaroxaban, dabigatran, apixaban) have become available as an alternative to warfarin anticoagulation in non-valvular atrial fibrillation (NVAF). Methods. MEDLINE and CENTRAL, regulatory agencies websites, clinical trials registers and conference proceedings were searched to identify randomised controlled trials of NOAC versus warfarin in NVAF. Two investigators reviewed all studies and extracted data on patient and study characteristics along with cardiovascular outcomes. Relative risks (RR) and 95% confidence intervals (CI) were estimated using a random effect meta-analysis. Results. Three clinical trials in 50,578 patients were included. The risk of non-hemorrhagic stroke and systemic embolic events (SEE) was similar with the NOAC and warfarin (; 95% –1.04), while the risk of intracranial bleeding (ICB) with the NOAC was lower than with warfarin (RR = 0.46; 95% CI = 0.33–0.65). We found differences in the effect size on all strokes and SEE depending on geographic region as well as on non-hemorrhagic stroke, SEE, bleeding and mortality depending on time in therapeutic range. Conclusion. The NOAC seem no more effective than warfarin for prevention of nonhemorrhagic stroke and SEE in the overall NVAF population, but are generally associated with a lower risk of ICB than warfarin. Antonio Gómez-Outes, Ana Isabel Terleira-Fernández, Gonzalo Calvo-Rojas, M. Luisa Suárez-Gea, and Emilio Vargas-Castrillón Copyright © 2013 Antonio Gómez-Outes et al. All rights reserved. The Role of Thrombophilia in Pregnancy Wed, 18 Dec 2013 14:46:19 +0000 Thrombotic disease is a major cause of peripartum morbidity and mortality worldwide. Development of thrombosis in pregnancy is multifactorial due to the physiologic changes of pregnancy—which induce a relative hypercoagulable state—as well as physical changes leading to increased stasis and also the effects of both the inherited and the acquired thrombophilias. In this review, we discuss the impact of each of these factors on the development of thrombosis as well as the evidence for the impact of pregnancy-associated thrombosis on pregnancy outcome. We then discuss the use of both prophylactic and therapeutic anticoagulation during pregnancy and the puerperium. We review the indications and dosing recommendations for administration of anticoagulation in a context of discussing the evidence including the lack of evidence and formal guidelines in this area. We briefly address the role of the new oral anticoagulants in pregnancy and conclude that significant further research in women with thrombophilias and pregnancy-associated thrombosis may help clarify the management of this condition in the future. Elisabeth M. Battinelli, Ariela Marshall, and Jean M. Connors Copyright © 2013 Elisabeth M. Battinelli et al. All rights reserved. Biomarkers of Coagulation and Fibrinolysis during Cemented Total Hip Arthroplasty with Pre- versus Postoperative Start of Thromboprophylaxis Mon, 16 Dec 2013 09:08:51 +0000 Venous thrombosis is common in elective hip surgery, and prophylaxis is recommended. Clinical trials suggest that the drug dose and timing of initiating prophylaxis significantly influence antithrombotic effectiveness and safety. We studied the time course and gradient of plasma coagulation and fibrinolysis during total hip arthroplasty (THA) in twenty patients that were randomly assigned to have the first dose of 5000 IU dalteparin subcutaneously (sc) injected 12 hours before or 6 hours after surgery. Baseline characteristics were similar in both groups. Specific biomarkers on coagulation (prothrombin fragment 1+2 (F1+2)) and fibrinolytic activity (plasmin/α2-antiplasmin complex (PAP) and D-dimer) were collected at six events during hospitalization and analysed. There were no significant group differences in the biomarkers at any time point. The highest concentrations were measured 6 hours after surgery and before the first postoperative injection. A marked decrease followed at the first postoperative day, and then a second increase in plasma concentrations was observed 6 days after surgery. This study showed that activation of coagulation and fibrinolysis by the operative trauma was the same when the first dose of dalteparin was injected 12 hours before or 6 hours after surgery. Pål O. Borgen, Ola E. Dahl, and Olav Reikeras Copyright © 2013 Pål O. Borgen et al. All rights reserved. Venous Thromboembolism in Critically Ill Cirrhotic Patients: Practices of Prophylaxis and Incidence Tue, 10 Dec 2013 08:30:32 +0000 Objectives. We compared venous thromboembolism (VTE) prophylaxis practices and incidence in critically ill cirrhotic versus noncirrhotic patients and evaluated cirrhosis as a VTE risk factor. Methods. A cohort of 798 critically ill patients followed for the development of clinically detected VTE were categorized according to the diagnosis of cirrhosis. VTE prophylaxis practices and incidence were compared. Results. Seventy-five (9.4%) patients had cirrhosis with significantly higher INR (2.2 ± 0.9 versus 1.3 ± 0.6, ), lower platelet counts (115,000 ± 90,000 versus 258,000 ± 155,000/μL, ), and higher creatinine compared to noncirrhotic patients. Among cirrhotics, 31 patients received only mechanical prophylaxis, 24 received pharmacologic prophylaxis, and 20 did not have any prophylaxis. Cirrhotic patients were less likely to receive pharmacologic prophylaxis (odds ratio, 0.08; 95% confidence interval (CI), 0.04–0.14). VTE occurred in only two (2.7%) cirrhotic patients compared to 7.6% in noncirrhotic patients (). The incidence rate was 2.2 events per 1000 patient-ICU days for cirrhotic patients and 3.6 events per 1000 patient-ICU days for noncirrhotics (incidence rate ratio, 0.61; 95% CI, 0.15–2.52). On multivariate Cox regression analysis, cirrhosis was not associated with VTE risk (hazard ratio, 0.40; 95% CI, 0.10–1.67). Conclusions. In critically ill cirrhotic patients, VTE incidence did not statistically differ from that in noncirrhotic patients. Hasan M. Al-Dorzi, Hani M. Tamim, Abdulaziz S. Aldawood, and Yaseen M. Arabi Copyright © 2013 Hasan M. Al-Dorzi et al. All rights reserved. A Systematic Review of the Utility of Residual Vein Obstruction Studies in Primary and Secondary Venous Thrombosis Tue, 19 Nov 2013 09:24:56 +0000 Background. Residual vein obstruction (RVO), the persistence of venous thrombosis with time and often after anticoagulation, may indicate a systemic prothrombotic condition. Prior studies have shown varying efficacy in using RVO as a risk factor for future venous thromboembolic (VTE) recurrence. Methods. To assess whether positive RVO imaging predicts recurrent VTE events, we performed a meta-analysis on studies in which patients with documented VTEs, anticoagulated for a minimum of 4 weeks, had repeat sonography to assess RVO and were subsequently followed for recurrent events. Results. Thirteen studies met inclusion criteria: 3531 patient VTE events with 3474 evaluable results were analyzed. The presence of RVO was associated with recurrence in all VTE (OR 1.93; 95% CI: 1.29, 2.89) and secondary VTE (OR 2.78; 95% CI: 1.41, 5.5) but not for primary VTE (OR 1.35; 95% CI: 0.87, 2.08). When cancer patients were eliminated from the secondary VTE group, there was no longer a significant association of RVO with VTE recurrence (OR 1.73; 95% CI: 0.81, 3.67) while in the subset of cancer patients, presence of RVO was associated with an increase in VTE recurrence risk (OR 5.14; 95% CI: 1.59, 16.65, ). Conclusions. We conclude that the presence of RVO is associated with recurrence in secondary VTE but not in primary VTE and that association may be driven by the subset with cancer. Murali Janakiram, Matthew Sullivan, Marina Shcherba, Shuang Guo, and Henny H. Billett Copyright © 2013 Murali Janakiram et al. All rights reserved. Use of Oral Anticoagulation Therapy in Atrial Fibrillation after Stroke: Results from a Nationwide Registry Sun, 17 Nov 2013 10:27:44 +0000 Background. The knowledge is still sparse about patient related factors, influencing oral anticoagulation therapy (OAC) rates, in stroke patients with atrial fibrillation (AF). Aims. To assess the use of OAC in ischemic stroke patients diagnosed with AF and to identify patient related factors influencing the initiation of OAC. Methods. In the nationwide Danish Stroke Registry we identified 55,551 patients admitted with acute ischemic stroke from 2003 to 2011. Frequency analysis was used to assess the use of OAC in patients with AF, and logistic regression was used to determine independent predictors of OAC. Results. 17.1% () of ischemic stroke patients had AF. OAC prescription rates were increasing, and in 2011 46.6% were prescribed OAC, 42.5% had a contraindication, and 3.7% were not prescribed OAC without a stated contraindication. Younger age, less severe stroke, and male gender were positive predictors of OAC, while excessive alcohol consumption, smoking, and institutionalization were negative predictors of OAC ( values < 0.05). Conclusions. Advanced age, severe stroke, female gender, institutionalization, smoking, and excessive alcohol consumption were associated with lower OAC rates. Contraindications were generally present in patients not in therapy, and the assumed underuse of OAC may be overestimated. Stine Funder Jespersen, Louisa M. Christensen, Anders Christensen, and Hanne Christensen Copyright © 2013 Stine Funder Jespersen et al. All rights reserved. Anticoagulation for Prosthetic Valves Mon, 04 Nov 2013 11:21:14 +0000 Implantation of prosthetic valve requires consideration for anticoagulation. The current guideline recommends warfarin on all mechanical valves. Dabigatran is the new generation anticoagulation medication which is taken orally and does not require frequent monitoring. This drug is approved for treatment for atrial fibrillation and venous thromboembolism, but the latest large trial showed that this drug increases adverse events when used for mechanical valve anticoagulation. On-X valve is the new generation mechanical valve which is considered to require less anticoagulation due to its flow dynamics. The latest study showed that lower anticoagulation level lowers the incidence of bleeding, while the risk of thromboembolism and thrombosis remained the same. Anticoagulation poses dilemma in cases such as pregnancy and major bleeding event. During pregnancy, warfarin can be continued throughout pregnancy and switched to heparin derivative during 6–12 weeks and >36 weeks of gestation. Warfarin can be safely started after 1-2 weeks of discontinuation following major bleeding episode. Tsuyoshi Kaneko and Sary F. Aranki Copyright © 2013 Tsuyoshi Kaneko and Sary F. Aranki. All rights reserved. Regulation of Vascular Function on Posttranscriptional Level Thu, 31 Oct 2013 09:15:29 +0000 Posttranscriptional control of gene expression is crucial for regulating plurality of proteins and functional plasticity of the proteome under (patho)physiologic conditions. Alternative splicing as well as micro (mi)RNA-mediated mechanisms play an important role for the regulation of protein expression on posttranscriptional level. Both alternative splicing and miRNAs were shown to influence cardiovascular functions, such as endothelial thrombogenicity and the vascular tone, by regulating the expression of several vascular proteins and their isoforms, such as Tissue Factor (TF) or the endothelial nitric oxide synthase (eNOS). This review will summarize and discuss the latest findings on the (patho)physiologic role of alternative splicing processes as well as of miRNAs on modulation of vascular functions, such as coagulation, thrombosis, and regulation of the vascular tone. Andreas Eisenreich Copyright © 2013 Andreas Eisenreich. All rights reserved. Postoperative Venous Thromboembolism Prophylaxis by General Surgeons in a Developing Country: A Survey Thu, 19 Sep 2013 15:37:42 +0000 Venous thromboembolism (VTE) is the most common preventable cause of hospital death. Several audits in the west have demonstrated that appropriate thromboprophylaxis is not being offered to a large number of surgical patients. Similar audits are lacking in the Indian population, and a perception exists among Indian surgeons that Indian patients are not susceptible to VTE. Hence we undertook a survey to analyze the existing knowledge and practice of VTE prophylaxis amongst general surgeons in India. A questionnaire-based survey was conducted on 100 active general surgeons. We found that 97% of surgeons had encountered VTE in their practice, and 49% had encountered mortality from pulmonary embolism. 64% of surgeons do not routinely score patients preoperatively for their VTE risk, and only 33% reported the presence of an institute-based protocol for the same. There was a wide disparity in the prophylaxis methods used for each risk group, particularly in the moderate-risk group. These findings suggest the need for adoption of institute-based protocols for prophylaxis and the evolution of Indian guidelines for VTE prophylaxis. Aniketh Venkataram, Shivashankar Santhosh, Deevish Dinakar, Shivananda Siddappa, Rajashekara Babu, and Sadashivaiah Shivaswamy Copyright © 2013 Aniketh Venkataram et al. All rights reserved. New Oral Anticoagulants in the Treatment of Pulmonary Embolism: Efficacy, Bleeding Risk, and Monitoring Wed, 10 Apr 2013 15:41:08 +0000 Anticoagulation therapy is mandatory in patients with pulmonary embolism to prevent significant morbidity and mortality. The mainstay of therapy has been vitamin-K antagonist therapy bridged with parenteral anticoagulants. The recent approval of new oral anticoagulants (NOACs: apixaban, dabigatran, and rivaroxaban) has generated significant interest in their role in managing venous thromboembolism, especially pulmonary embolism due to their improved pharmacokinetic and pharmacodynamic profiles, predictable anticoagulant response, and lack of required efficacy monitoring. This paper addresses the available literature, on-going clinical trials, highlights critical points, and discusses potential advantages and disadvantages of the new oral anticoagulants in patients with pulmonary embolism. Kelly M. Rudd and Elizabeth (Lisa) M. Phillips Copyright © 2013 Kelly M. Rudd and Elizabeth (Lisa) M. Phillips. All rights reserved. Prevention and Treatment of Venous Thromboembolism with New Oral Anticoagulants: A Practical Update for Clinicians Thu, 21 Feb 2013 14:51:43 +0000 Traditional anticoagulants, such as warfarin and enoxaparin, have several limitations, including parenteral administration, need for laboratory monitoring, and ongoing dose adjustment, which may limit optimal patient care. Newer oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran etexilate) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban, and edoxaban), have been developed to overcome these drawbacks, and thereby improve patient care. Several of these agents have been approved for use in the prevention and treatment of venous and/or systemic thromboembolism. The objective of this paper is to provide an overview of the available clinical trial data for these new oral anticoagulants in the prevention and treatment of venous thromboembolism and a practical update for clinicians. Nay Min Tun and Thein Hlaing Oo Copyright © 2013 Nay Min Tun and Thein Hlaing Oo. All rights reserved. The Efficacy and Safety of Rivaroxaban for Venous Thromboembolism Prophylaxis after Total Hip and Total Knee Arthroplasty Thu, 21 Feb 2013 11:57:17 +0000 Venous thromboembolism (VTE) is a common complication after total hip and total knee arthroplasty. Currently used methods of VTE prophylaxis after these procedures have important limitations, including parenteral administration, and unpredictable plasma levels requiring frequent monitoring and dose adjustment leading to decreased patient compliance with recommended guidelines. New oral anticoagulants have been demonstrated in clinical trials to be equally efficacious to enoxaparin and allow for fixed dosing without the need for monitoring. Rivaroxaban is one of the new oral anticoagulants and is a direct factor Xa inhibitor that has demonstrated superior efficacy to that of enoxaparin. However, the data also suggest that rivaroxaban has an increased risk of bleeding compared to enoxaparin. This paper reviews the available data on the efficacy and safety of rivaroxaban for VTE prophylaxis after total hip and total knee arthroplasty. Robert D. Russell, William R. Hotchkiss, Justin R. Knight, and Michael H. Huo Copyright © 2013 Robert D. Russell et al. All rights reserved. Towards Personalized Medicine Based on Platelet Function Testing for Stent Thrombosis Patients Tue, 25 Dec 2012 14:22:34 +0000 Stent thrombosis (ST) is a severe and feared complication of coronary stenting. Patients who have suffered from ST are usually treated according to the “one-size-fits-all” dosing regimen of aspirin and clopidogrel. Many ST patients show high on-treatment platelet reactivity (HPR) despite this antiplatelet therapy (APT). It has been shown that HPR is a risk factor for major adverse cardiac events. Therefore, ST patients with HPR are at a high risk for recurrent atherothrombotic events. New insights into the variable response to clopidogrel and the advent of stronger P2Y12 inhibitors prasugrel and ticagrelor have changed the attention from a fixed APT treatment strategy towards “personalized APT strategies.” Strategies can be based on platelet function testing, which gives insight into the overall response of a patient to APT. At our outpatient ST clinic, we practice personalized APT based on platelet function testing to guide the cardiologist to a presumed optimal antiplatelet treatment of ST patients. Beside results of platelet function testing, comedication, clinical characteristics, and genetics have to be considered to decide on personalized APT. Ongoing studies have yet to reveal the optimal personalized APT strategy for cardiologists to prevent their patients from atherothrombotic and bleeding events. Thea Cornelia Godschalk, Christian Marcus Hackeng, and Jurriën Maria ten Berg Copyright © 2012 Thea Cornelia Godschalk et al. All rights reserved. Pathologic Etiologies of Late and Very Late Stent Thrombosis following First-Generation Drug-Eluting Stent Placement Wed, 21 Nov 2012 10:12:03 +0000 Several randomized and observational studies have reported steady increase in cumulative incidence of late and very late ST (LST/VLST) following first-generation drug-eluting stents (DES: sirolimus-(SES) and paclitaxel-(PES)) up to 5 years. Pathologic studies have identified uncovered struts as the primary substrate responsible for LST/VLST following DES, where delayed arterial healing is associated with stent struts penetrating into the necrotic core, long/overlapping stents, and bifurcation stenting especially in flow divider region. Grade V stent fracture also induces LST/VLST and restenosis. Hypersensitivity reaction is exclusive to SES as an etiology of LST/VLST, whereas malapposition secondary to excessive fibrin deposition is associated with PES. Uncovered struts can be identified in SES and PES with duration of implant beyond 12 months, particularly in stents placed for “off-label” indications. Neoatherosclerosis is another important contributing factor for VLST in DES and bare metal stents (BMS); however, DES shows rapid and more frequent development of neoatherosclerosis than BMS. Future pathologic studies should address the long-term safety of newer generation DES including zotarolimus- and everolimus-eluting stents in terms of the improvement in reendothelialization, decreased inflammation and fibrin deposition as well as a lower incidence of stent fracture-related adverse events, and reduced neoatherosclerosis, which likely contribute to the decreased risk of LST/VLST and better patient outcomes. Fumiyuki Otsuka, Masataka Nakano, Elena Ladich, Frank D. Kolodgie, and Renu Virmani Copyright © 2012 Fumiyuki Otsuka et al. All rights reserved. Anti-Phospholipid Antibodies in Patients Undergoing Total Joint Replacement Surgery Wed, 31 Oct 2012 10:05:56 +0000 Background. Patients undergoing joint replacement remain at increased risk for venous thromboembolism (VTE) compared to other types of surgery, regardless of thromboprophylactic regimen. The pathophysiologic processes rendering this group of patients at risk for VTE are multifactorial. Procedure-specific and patient-specific exposures play a role in the postoperative development of VTE, including the development of anti-phospholipid antibodies (aPL). Methods. We measured three aPL (anti-cardiolipin, anti- glycoprotein, and lupus anticoagulant) in 123 subjects undergoing total knee or hip arthroplasty to describe the presence of these antibodies preoperatively and to describe the rate of postoperative seroconversion among those people who were negative preoperatively. Postoperative antibodies were measured at day 7, 14, and 21. Results. The prevalence of aPL antibodies in the preoperative period was 44%, positive subjects were more likely to be smokers () and were less likely to have undergone a previous arthroplasty procedure (). Subjects seroconverted in a 21 day postoperative period at a rate of 79%. Conclusions. These pilot data suggest that the prevalence of aPL in this population both preoperatively and postoperatively is higher than previously expected. Further studies are needed to describe aPL in a larger population and to establish their clinical significance in populations undergoing joint replacement surgeries. Melissa Simpson, Michael J. Sanfelippo, Adedayo A. Onitilo, James K. Burmester, William Hocking, Steven H. Yale, and Joseph J. Mazza Copyright © 2012 Melissa Simpson et al. All rights reserved. Thrombosis and Aspirin: Clinical Aspect, Aspirin in Cardiology, Aspirin in Neurology, and Pharmacology of Aspirin Sun, 21 Oct 2012 11:22:16 +0000 Christian Doutremepuich Copyright © 2012 Christian Doutremepuich. All rights reserved. The Role of Anticoagulation Clinics in the Era of New Oral Anticoagulants Sun, 14 Oct 2012 16:32:45 +0000 Anticoagulation Clinics (ACs) are services specialized in management of patients on anticoagulant treatment. At present, ACs manage patients chiefly on antivitamin K antagonists (AVKs), but patient population has already changed in the last few years, because of an increase of treatments with other anticoagulant drugs, which require different management systems. The strong increase in the number of patients at AC, mainly on long-term treatment, has determined the development of web management, through telemedicine systems, improving the quality of life and maintaining the same clinical quality levels. New oral anticoagulants (NOAs) have shown to be as effective as AVK antagonists in stroke prevention in atrial fibrillation and for treatment of venous thromboembolism in addition to VTE prophylaxis in orthopaedic surgery, when administered at a fixed dose, but patient adherence and compliance are crucial for good quality treatment. At present, lacking data from the real world, an oversimplification of treatment with NOAs could cause unjustified risks for patients and also a possible future underuse of good drugs. For these reasons the vigilance must be high and ACs can have a crucial role in defining which is the best management for NOA patients and how to do it, as it happened for AVKs. Sophie Testa, Oriana Paoletti, Anke Zimmermann, Laura Bassi, Silvia Zambelli, and Emilia Cancellieri Copyright © 2012 Sophie Testa et al. All rights reserved. Thromboembolic Prophylaxis in Total Joint Arthroplasty Sun, 16 Sep 2012 08:56:00 +0000 Approximately 775,000 hip and knee arthroplasties are performed yearly in the United States, with a dramatic increase expected. Patients having hip and knee arthroplasties are at high risk of developing a venous thromboembolism. The American College of Chest Physicians (ACCP) and the American Academy of Orthopedic Surgeons (AAOS) have updated guidelines, which outline new prophylactic strategies. Factor Xa inhibitor rivaroxaban has a new recommendation by ACCP and is gradually being adopted by the joint arthroplasty community as an effective oral agent. Other more well-known agents including warfarin, low-molecular-weight heparin, aspirin, and fondaparinux continue to be options for prophylaxis. While the goal of prophylaxis continues to be the prevention of venous thromboemboli and pulmonary emboli, it is important to consider the increased bleeding risk associated with their use. The most recent ACCP and AAOS guidelines give clinicians a greater autonomy in choosing a prophylactic agent with greater emphasis placed on dialogue between the surgeon and patient as to the choice of prophylaxis. David Knesek, Todd C. Peterson, and David C. Markel Copyright © 2012 David Knesek et al. All rights reserved. Management of Venous Thromboembolism in Patients with Advanced Gastrointestinal Cancers: What Is the Role of Novel Oral Anticoagulants? Tue, 11 Sep 2012 15:50:29 +0000 Venous thromboembolism (VTE) is a frequent complication of gastrointestinal cancers that increases morbidity and may impact mortality. Low-molecular-weight heparins (LMWHs) and vitamin K antagonists (VKAs) are standard anticoagulation options for the ambulatory gastrointestinal cancer patient with VTE, but both of these agents are challenging to use for various reasons. Novel oral anticoagulants (NOAs) are new, orally available anticoagulants designed to be easier to administer with more reliable pharmacokinetics that eliminate the need for frequent monitoring of various laboratory parameters. This paper reviews the existing efficacy and safety data for the use of NOAs dabigatran etexilate, rivaroxaban, and apixaban and discusses the potential role of these agents in the management of gastrointestinal cancer-related VTE. Ludmila Katherine Martin and Tanios Bekaii-Saab Copyright © 2012 Ludmila Katherine Martin and Tanios Bekaii-Saab. All rights reserved. Stroke Prevention in Atrial Fibrillation: Understanding the New Oral Anticoagulants Dabigatran, Rivaroxaban, and Apixaban Mon, 10 Sep 2012 15:10:24 +0000 Unlike vitamin K antagonists (VKAs), the new oral anticoagulants (NOACs)—direct thrombin inhibitor, dabigatran, and direct activated factor X inhibitors, rivaroxaban, and apixaban—do not require routine INR monitoring. Compared to VKAs, they possess relatively rapid onset of action and short halflives, but vary in relative degrees of renal excretion as well as interaction with p-glycoprotein membrane transporters and liver cytochrome P450 metabolic enzymes. Recent completed phase III trials comparing NOACs with VKAs for stroke prevention in atrial fibrillation (AF)—the RE-LY, ROCKET AF, and ARISTOTLE trials—demonstrated at least noninferior efficacy, largely driven by significant reductions in haemorrhagic stroke. Major and nonmajor clinically relevant bleeding rates were acceptable compared to VKAs. Of note, the NOACs caused significantly less intracranial haemorrhagic events compared to VKAs, the mechanisms of which are not completely clear. With convenient fixed-dose administration, the NOACs facilitate anticoagulant management in AF in the community, which has hitherto been grossly underutilised. Guidelines should evolve towards simplicity in anticipation of greater use of NOACs among primary care physicians. At the same time, the need for caution with their use in patients with severely impaired renal function should be emphasised. Tan Ru San, Mark Yan Yee Chan, Teo Wee Siong, Tang Kok Foo, Ng Kheng Siang, Sze Huar Lee, and Ching Chi Keong Copyright © 2012 Tan Ru San et al. All rights reserved. Reversible Crystallization of Argatroban after Subcutaneous Application in Pigs Mon, 03 Sep 2012 08:49:32 +0000 Argatroban is a thrombin inhibitor used as anticoagulant in patients with heparin-induced thrombocytopenia. It is usually administered as an intravenous bolus followed by infusion. Nevertheless, its pharmacokinetics after subcutaneous administration is unknown. The aim of this study was to assess the pharmacokinetics of two different formulations of argatroban in pigs after subcutaneous administration. Antithrombotic activity in plasma was determined by ecarin chromogenic assay. To visualize the formation of crystals, argatroban was administered to rats into the subcutaneous tissue exposed after removing the skin, and the injection site was photographed at different times. After subcutaneous administration of a sorbitol/ethanol formulation of argatroban in pigs was observed a slow absorption phase was followed by long-lasting levels of this inhibitor. 𝐶max and AUC(0−24) showed dose-dependent increases, while elimination half-life and 𝑡max value did not change significantly with dose. In contrast, saline-dissolved argatroban showed a faster absorption phase followed by a shorter elimination half-life. Argatroban dissolved in sorbitol/ethanol leads to long-lasting plasma levels due to the formation and permanent dissolution of a crystalline depot at the injection place. This represents a simple way to deliver argatroban continuously over an extended period which can be beneficial for prophylaxis or treatment of chronic coagulations disorders. Mercedes Lopez and Goetz Nowak Copyright © 2012 Mercedes Lopez and Goetz Nowak. All rights reserved. Actual Situation of Thromboembolic Prophylaxis in Obesity Surgery: Data of Quality Assurance in Bariatric Surgery in Germany Mon, 09 Jul 2012 18:18:37 +0000 Background. Evidence-based data on optimal approach for prophylaxis of deep venous thrombosis (VTE) and pulmonary embolism (PE) in bariatric operations is discussed. Using antithrombotic prophylaxis weight adjusted the risk of VTE and its complications have to be balanced with the increased bleeding risk. Methods. Since 2005 the current situation for bariatric surgery has been examined by quality assurance study in Germany. As a prospective multicenter observational study, data on the type, regimen, and time course of VTE prophylaxis were documented. The incidences of clinically diagnosed VTE or PE were derived during the in-hospital course and follow up. Results. Overall, 11,835 bariatric procedures were performed between January 2005 and December 2010. Most performed procedures were 2730 gastric banding (GB); 4901 Roux-en-Y-gastric bypass (RYGBP) procedures, and 3026 sleeve gastrectomies (SG). Study collective includes 72.5% (mean BMI 48.1 kg/m2) female and 27.5% (mean BMI 50.5 kg/m2) male patients. Incidence of VTE was 0.06% and of PE 0.08%. Conclusion. VTE prophylaxis regimen depends on BMI and the type of procedure. Despite the low incidence of VTE and PE there is a lack of evidence. Therefore, prospective randomized studies are necessary to determine the optimal VTE prophylaxis for bariatric surgical patients. Christine Stroh, D. Luderer, R. Weiner, T. Horbach, K. Ludwig, F. Benedix, Stefanie Wolff, C. Knoll, H. Lippert, and T. Manger Copyright © 2012 Christine Stroh et al. All rights reserved. Factor V-Leiden Mutation: A Common Risk Factor for Venous Thrombosis among Lebanese Patients Tue, 12 Jun 2012 11:06:39 +0000 Aim. Lebanon exhibits one of the highest prevalences of factor V-Leiden (FVL) in the world (14.4%). The aim of this study is to evaluate the incidence of FVL mutation among Lebanese patients with lower extremity venous thrombosis. Material and Methods. From January 2003 to January 2011, 283 consecutive Lebanese patients, diagnosed with deep venous thrombosis (DVT) by duplex scan, were retrospectively reviewed. FVL mutation was tested among patients with conditions highly suggestive of hypercoagulation states (65 patients). Results. FVL mutation was detected among 56.9% of patients, 68.6% of patients younger than 50 years, and 43.4% of patients older than 50 years (𝑃=0.041). FVL mutation was commonly reported in young adults, in patients with pregnancy, estrogen drugs, recurrent DVT, and resistance to anticoagulation. Conclusion. The high rate of FVL mutation observed among Lebanese patients with venous thrombosis is related to the high prevalence of this mutation in the Lebanese population. Thrombophilia screening should be tailored to accommodate a population's risk factor. In countries with high prevalence of FVL, this mutation should be screened among patients younger than 50 years and patients with situations highly suggestive of hypercoagulation states. Raghid Kreidy Copyright © 2012 Raghid Kreidy. All rights reserved.