fondaparinux and Pulmonary-Embolism

Venous thromboembolism (VTE) is a major complication of trauma. Currently, there are few studies summarising the evidence for prophylaxis in trauma settings. This review provides evidence for the use of VTE prophylactic interventions in trauma patients to produce evidence-based guidelines.. A PRISMA-compliant review was conducted from Sep 2021 to June 2023, using Embase, Medline and Google Scholar. The inclusion criteria were: randomized-controlled trials (RCTs) in English published after 2000 of adult trauma patients comparing VTE prophylaxis interventions, with a sample size higher than 20. The network analysis was conducted using RStudio. The results of the pairwise comparisons were presented in the form of a league table. The quality of evidence and heterogeneity sensitivity were assessed. The primary outcome focused on venous thromboembolism (VTE), and examined deep vein thrombosis (DVT) and pulmonary embolism (PE) as separate entities. The secondary outcomes included assessments of bleeding and mortality. PROSPERO registration: CRD42021266393.. Of the 7,948 search results, 23 studies with a total of 21,312 participants fulfilled screening criteria, which included orthopaedic, spine, solid organ, brain, spinal cord, and multi-region trauma. Of the eight papers comparing chemical prophylaxis medications in patients with hip or lower limb injuries, fondaparinux and enoxaparin were found to be significantly superior to placebo in respect of prevention of DVT, with no increased risk of bleeding. Regarding mechanical prophylaxis, meta-analysis of two studies of inferior vena cava filters failed to provide significant benefits to major trauma patients.. Enoxaparin and fondaparinux are safe and effective options for VTE prevention in trauma patients, with fondaparinux being a cheaper and easier administration option between the two. Inconclusive results were found in mechanical prophylaxis, requiring more larger-scale RCTs.

Topics: Adult; Anticoagulants; Enoxaparin; Fondaparinux; Hemorrhage; Humans; Multiple Trauma; Network Meta-Analysis; Pulmonary Embolism; Venous Thromboembolism

Many centres have noticed a high number of venous thromboembolism (VTE) events among critically ill inpatients with COVID-19 pneumonia. The aims of this study were (1) to summarise the reported risk of VTE associated with COVID-19 infections and (2) to summarise guidance documents on thromboprophylaxis in COVID-19 patients, in a systematic review.. We systematically searched for peer-reviewed evidence on the risk of VTE in patients with COVID-19, in PubMed, Embase and Twitter, and for guidelines or guidance documents for thromboprophylaxis, from international or national societies relevant to the field of thrombosis and haemostasis, up to April 30 2020.. We found 11 studies (1 clinical trial, 7 retrospective cohorts and 3 prospective cohorts), which included a range of 16 to 388 in patients with COVID-19 (total of 1369 inpatients). The diagnoses of COVID-19 and VTE were of high quality, but the follow-up was often unclear. Most studies reported universal in-hospital thromboprophylaxis. Among all inpatients and among intensive care unit (ICU) inpatients with COVID-19, reported risks of VTE were 4.4–8.2% (three studies) and 0–35.3% (six studies), respectively. Two studies at least partially screened for VTE in ICU inpatients with COVID-19, and found risks of 24.7–53.8%. We found 12 guidelines for thromboprophylaxis of COVID-19 patients. The majority suggested universal pharmacological thromboprophylaxis in all COVID-19 inpatients, but there was heterogeneity in the suggested intensity of thromboprophylaxis: seven advised considering intensified doses of heparin according to the clinical or biological severity of the disease, especially in the ICU setting.. Venous thromboembolism very commonly complicates the clinical course of inpatients with COVID-19, despite thromboprophylaxis. The risk appears highest among critically ill inpatients. We found no estimates of risks among outpatients. Many questions remain unresolved, as delineated by the heterogeneity of national and international guidelines. This situation calls for fast randomised clinical trials, comparing different schemes of thromboprophylaxis in COVID-19 inpatients.

Topics: Anticoagulants; Betacoronavirus; Coronavirus Infections; COVID-19; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Pandemics; Pneumonia, Viral; Practice Guidelines as Topic; Pulmonary Embolism; Risk; SARS-CoV-2; Venous Thromboembolism; Venous Thrombosis

The aim was to review the relative efficacy and safety of anticoagulation for managing venous thromboembolism (VTE) in patients with cancer.. A systematic review and meta-analysis was carried out. On 17 May 2018 the MEDLINE and Scopus databases were searched for randomised controlled trials (RCTs). Eligible RCTs had to be performed in patients with cancer exclusively or to report results on a subset of patients with cancer. The main study outcomes (efficacy/recurrent VTE and safety/bleeding events) were expressed as risk ratios (RR) with a 95% confidence interval (CI). The quality of evidence was assessed following the GRADE method.. Twenty-three RCTs with 6980 patients were identified. Low molecular weight heparins (LMWHs) were more effective than vitamin K antagonists (VKAs) in preventing recurrent VTE (RR 0.58, 95% CI 0.45-0.75) and deep vein thrombosis (RR 0.44, 95% CI 0.29-0.69) but not pulmonary embolism (PE), bleeding, or overall mortality. Direct oral anticoagulants (DOACs) were more effective than VKAs in preventing recurrent VTE (RR 0.65, 95% CI 0.45-0.95) but not DVT, PE, overall mortality, or bleeding. However, anti-Xa DOACs were more effective (RR for VTE 0.64, 95% CI 0.42-0.97) and caused less bleeding than VKAs, although major bleeding was reduced only with DOACs not requiring initial parenteral anticoagulation (RR 0.45, 95% CI 0.21-0.97). In a direct comparison, DOACs were more effective than LMWHs in preventing VTE recurrence (RR 0.64, 95% CI 0.45-0.90) but caused more major bleeding (RR 1.75, 95% CI 1.10-2.77), with no difference in fatal bleeding and overall mortality. Quality of evidence, where sufficient, was mostly moderate or high.. Compared with VKAs, LMWHs and DOACs are more effective in treating VTE, but the former caused less bleeding. DOACs are more effective than LMWHs in preventing VTE recurrence but may carry a higher risk of major bleeding, pending additional information by ongoing trials.

Topics: Anticoagulants; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Oligosaccharides; Pulmonary Embolism; Secondary Prevention; Venous Thromboembolism; Venous Thrombosis; Vitamin K

The initial treatment of haemodynamically stable patients with pulmonary embolism (PE) has dramatically changed since the introduction of low molecular weight heparins (LMWHs). With the recent discovery of the direct oral anticoagulant drugs (DOACs), initial treatment of PE will be simplified even further. In several large clinical trials it has been demonstrated that DOACs are not inferior to standard therapy for the initial treatment of PE, and because of their practicability they are becoming the agents of first choice. However, many relative contraindications to DOACs were exclusion criteria in the clinical trials. Therefore, LMWHs will continue to play an important role in initial PE treatment and in some cases there still is a role for unfractionated heparin (UFH). In this review we will give an overview of the biophysical, pharmacokinetic and pharmacodynamic properties of anticoagulants currently available for the initial management of PE. In addition, we will provide a comprehensive overview of the indications for the use of UFH, LMWHs and DOACs in the initial management of PE from a pharmacokinetic/-dynamic point of view.

Topics: Acute Disease; Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Fibrinolytic Agents; Fondaparinux; Hemodynamics; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Treatment Outcome

Patients undergoing surgery are at an increased risk of VTE. Since the early 1990s the prevention of VTE has been dominated by the administration of low-molecular weight heparin during admission. New oral anticoagulants have been extensively researched and have increased in popularity. This chapter reviews why surgical patients are at increased risk of VTE and summaries both the pharmacological and mechanical methods of prophylaxis available.

Topics: Age Factors; Anticoagulants; Communicable Diseases; Dabigatran; Dehydration; Fondaparinux; Heparin, Low-Molecular-Weight; Hormone Replacement Therapy; Humans; Neoplasms; Obesity; Polysaccharides; Primary Prevention; Pulmonary Embolism; Risk Factors; Surgical Procedures, Operative; Venous Thromboembolism; Venous Thrombosis

Venous thromboembolism (VTE), manifesting as either deep vein thrombosis or pulmonary embolism, is common worldwide including in Japan. The number of patients clinically diagnosed with VTE is increasing with the majority of cases occurring out-of-hospital and of milder severity. Cancer is the largest risk factor for VTE and VTE in cancer patients confers an increased 1-year mortality rate. However, the majority of VTE cases are considered "idiopathic" or "unprovoked." The limited efficacies of unfractionated heparin and warfarin have stimulated the development of new anticoagulant therapies. Recently, parenteral and oral administration of the Xa inhibitors fondaparinux and edoxaban, respectively, was approved in Japan. These agents have the potential to provide safer and more efficacious treatment options for VTE. Although further randomized studies are required to validate the utility of these agents, they are expected to substantially improve quality of life in VTE patients. This review summarizes the current status of VTE management in Japan focusing on current epidemiology and recent advances in anticoagulant therapy.

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Japan; Polysaccharides; Pulmonary Embolism; Pyridines; Quality of Life; Risk Factors; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Warfarin

The risk of recurrent thromboembolic disorders in the 10-year period following an episode of unprovoked venous thromboembolism (VTE) ranges between 30 and 50%, the rate being higher in patients with primary deep venous thrombosis (DVT) than in those with primary pulmonary embolism (PE). The clinical presentation with primary PE increases by more than three times the risk of a new PE episode over that with isolated DVT. Baseline parameters that increase this risk are the proximal location of DVT, obesity, old age and male sex, whereas the role of thrombophilia is controversial. An increasing role is played by post-baseline parameters such as the ultrasound assessment of residual vein thrombosis and the determination of D-dimer. While the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, new scenarios are being offered by the identification of risk stratification models and by strategies that have the potential to help identify patients in whom anticoagulation can be safely discontinued, such as those that incorporate the assessment of D-dimer and residual vein thrombosis. New opportunities are being offered by low-dose aspirin, which has recently been reported to decrease by more than 30% the risk of recurrent events without increasing the bleeding risk; and especially by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving at least the same effectiveness, do not require laboratory monitoring, and can be used immediately after the thrombotic episode.

Topics: Age Factors; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Dabigatran; Disease Management; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Fondaparinux; Humans; Male; Morpholines; Obesity; Polysaccharides; Postthrombotic Syndrome; Pulmonary Embolism; Risk Assessment; Risk Factors; Rivaroxaban; Secondary Prevention; Sex Factors; Thiophenes; Thrombophilia; Ultrasonography; Venous Thromboembolism; Venous Thrombosis; Warfarin

The introduction of factor Xa inhibitors advocated the initiation of clinical trials that addressed the value of anticoagulation in patients with hemodynamically stable primary pulmonary embolism (PE). In the Matisse trial in patients with PE, fondaparinux administered at therapeutic doses followed by vitamin K antagonists (VKA) has shown a comparable efficacy and safety profile to that seen with intravenous adjusted-dose unfractionated heparin/VKA. A long-acting derivative of fondaparinux, idraparinux, failed to achieve similar results. On the other hand, the Cassiopea study revealed that once weekly injections of idrabiotaparinux, a slightly modified form of idraparinux, have similar efficacy and better safety profile compared to VKAs in the long-term treatment of patients with PE. However, the inconvenient parenteral administration of both fondaparinux and idrabiotaparinux limits their routine clinical use. The availability of antithrombotic compounds that can be administered orally in fixed dose, owing to their predictable pharmacokinetics and pharmacodynamics, and have a lower potential for drug and food interactions has opened new horizons for the treatment of patients with PE. The Einstein PE, Amplify and Hokusai studies, conducted with rivaroxaban, apixaban and edoxaban, respectively, showed that for the treatment of PE they possess a more favorable benefit-to-risk profile than the conventional antithrombotic drugs. In addition, rivaroxaban and apixaban make it possible to treat uncomplicated PE patients from the beginning, without the need for the parenteral administration of heparins or fondaparinux, and edoxaban allows the treatment of fragile patients with lower doses. All of them cover a wide spectrum of clinical presentations, including PE patients at intermediate risk.

Topics: Anticoagulants; Factor Xa Inhibitors; Fondaparinux; Humans; Polysaccharides; Pulmonary Embolism; Rivaroxaban

The management of thromboprophylaxis in patients with pelvic and acetabular fractures remains a highly controversial topic within the trauma community. Despite anticoagulation, venous thromboembolism (VTE) remains the most common cause of surgical morbidity and mortality in this high-risk patient group. Although various thromboprophylactic regimes are employed, evidence relating to the most effective method remains unclear. Controversies surrounding screening, the use of prophylactic inferior vena cava filters (IVCF) and chemothromboprophylaxis in polytraumatised patients, particularly those with pelvic and acetabular fractures, form the basis of considerable debate. With the absence of a well-designed clinical trial and the presence of ongoing controversies within the literature, this review will explore current treatment options available to trauma surgeons and highlight differing scientific opinions, providing an update on the role of screening and current available preventative measures. We cover existing as well as recent advances in chemical thromboprophylactic agents and discuss external mechanical compression devices, the usefulness of serial duplex ultrasonography and the role of extended chemothromboprophylaxis on discharge. The evidence behind prophylactic IVCF is also considered, along with reported complication profiles. We conclude with a proposed protocol for use in major trauma centres, which can form the basis of local policy for the prevention of VTE in trauma patients with pelvic and acetabular fractures.

Topics: Acetabulum; Anticoagulants; Aspirin; Benzimidazoles; beta-Alanine; Coumarins; Dabigatran; Fondaparinux; Fractures, Bone; Heparin; Humans; Mass Screening; Morpholines; Multiple Trauma; Pelvis; Polysaccharides; Pulmonary Embolism; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Thiophenes; Vena Cava Filters; Venous Thromboembolism

Topics: Acute Disease; Animals; Anticoagulants; Clinical Trials as Topic; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Interactions; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Humans; Injections, Subcutaneous; Polysaccharides; Pulmonary Embolism; Venous Thrombosis

Recent data on lower-limb superficial-vein thrombosis (SVT) may substantially impact its clinical management. Particularly, the clear confirmation that SVT is closely linked to deep-vein thrombosis (DVT) or pulmonary embolism (PE) highlights the potential severity of the disease. DVT or PE is diagnosed in 20-30% of SVT patients. Moreover, clinically relevant symptomatic thromboembolic events complicate isolated SVT (without concomitant DVT or PE at diagnosis) in 4-8% of patients. For the first time, an anticoagulant treatment, once-daily 2.5 mg fondaparinux for 45 days, was demonstrated to be effective and safe for preventing these symptomatic thromboembolic events in patients with lower-limb isolated SVT in the randomized, placebo-controlled CALISTO study. More recent data from another randomized trial support these findings. New recommendations on the management of SVT patients, including complete ultrasonography examination of the legs and, in patients with isolated SVT, prescription of once-daily 2.5 mg fondaparinux subcutaneously for 45 days on top of symptomatic treatments, may be proposed, wherever the cost of fondaparinux is acceptable. Superficial-vein thrombosis (SVT) of the lower limbs has long been regarded as a benign, self-limiting disease, expected to resolve spontaneously and rapidly, and requiring only symptomatic treatments [1,2]. However, the perception of this disease is now changing with the recent publication of data indicating its potential severity [3] and showing for the first time the benefit of a therapeutic strategy based on the administration of an anticoagulant treatment [4]. The overall management of this frequent disease therefore needs to be reconsidered.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Drug Administration Schedule; Female; Fondaparinux; France; Humans; Leg; Male; Middle Aged; Polysaccharides; Pulmonary Embolism; Randomized Controlled Trials as Topic; Venous Thrombosis

Approximately 10% of all patients with acute pulmonary embolism (PE) die within the first three months after diagnosis. However, PE is not universally life-threatening, but covers a wide spectrum of clinical severity and death risk. Thrombolytic treatment is indicated patients with acute massive PE who are at high risk for early death, i.e. those patients who present with arterial hypotension and shock. On the other hand, low molecular-weight heparin or fondaparinux is adequate treatment for most normotensive patients with PE. Recombinant tissue plasminogen activator, given as 100 mg infusion over 2 h, is the treatment of choice for patients with PE, although older regimens using urokinase or streptokinase are also efficacious. Beyond the relatively small numbers of patients with massive, high-risk PE as a target population for thrombolysis, there is increasing awareness of the need for risk stratification of normotensive patients and the search for an intermediate-risk group (also called submassive PE). Recent meta-analyses of cohort studies suggest that imaging of the right ventricle or biomarkers of myocardial injury alone may be insufficient for guiding therapeutic decisions. Instead, accumulating evidence appears to support strategies which combine the information provided by an imaging procedure with a biomarker test. These data provide the rationale for a large multinational randomized trial which has set out to determine whether normotensive patients with right ventricular dysfunction, detected by echocardiography or computed tomography, plus evidence of myocardial injury as indicated by a positive troponin test, may benefit from early thrombolytic treatment. This study, which is underway in 13 European countries, will enroll a total of 1000 patients and will be completed in 2012. Together with a parallel trial currently being conducted in the United States, it will hopefully answer the question whether thrombolysis is indicated in submassive PE, thus terminating a 40-year-old debate and filling an important gap in our management concept for acute pulmonary embolism.

Topics: Acute Disease; Biomarkers; Clinical Trials as Topic; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Radiography; Risk Factors; Streptokinase; Thrombolytic Therapy; Tissue Plasminogen Activator; Troponin; Urokinase-Type Plasminogen Activator; Ventricular Dysfunction, Right

Surgery for pelvic or acetabular fractures carries a high risk of deep-vein thrombosis (DVT). Reports indicate that fondaparinux is a more effective thromboprophylactic agent than low molecular weight heparin (LMWH) after major orthopaedic surgery. The safety and efficacy of fondaparinux was evaluated in a new protocol used for DVT prophylaxis. One hundred and twenty seven patients with pelvic or acetabular fractures received either fondaparinux or enoxaparin and were analysed in a historical non-concurrent study. Specific review points included clinical deep-vein thrombosis (DVT) or pulmonary embolism (PE) and evidence of adverse effects such as bleeding or allergic reactions. Two patients that received enoxaparin were found to have a DVT and one patient had a PE. There was no documented DVT or PE in patients that received fondaparinux. The mean number of units of blood transfused postoperatively was higher in the enoxaparin group; however, multivariate regression modelling demonstrated no significant difference between the groups. The most current large randomised controlled studies investigating the administration of fondaparinux following joint arthroplasty or hip fracture surgery, have demonstrated a slight increase or a similar number of bleeding events in patients treated with fondaparinux when compared to those treated with enoxaparin. The current report supports that fondaparinux, in patients with pelvic and acetabular fractures, can be equally effective as enoxaparin and not associated with adverse bleeding events.

Topics: Acetabulum; Adult; Anticoagulants; Enoxaparin; Female; Fondaparinux; Fractures, Bone; Humans; Male; Orthopedic Procedures; Pelvic Bones; Polysaccharides; Postoperative Hemorrhage; Pulmonary Embolism; Venous Thrombosis; Wounds and Injuries

Superficial vein thrombosis (SVT) occurs at least as frequent as deep vein thrombosis (DVT), and shares common risk factors with venous thromboembolism. The CALISTO trial was the first to provide specific recommendations for the pharmacologic treatment of SVT. Before treatment is initiated, an accompanying DVT must be excluded and the proximal extension of the SVT assessed. If the proximal extension of the thrombus is closer than 3 cm towards the deep vein system, it should be treated like DVT. Under certain conditions treatment with fondaparinux is indicated in acute symptomatic SVT. Furthermore, compression treatment is recommended. Extracranial carotid artery stenosis can be treated by either surgical thrombarterectomy or catheter based endovascular stent implantation. Trials comparing the two methods have not provided conclusive results on whether the two strategies are equally safe and effective. Considering the latest data from RCTs, careful patient selection (symptoms, comorbidities, age, anatomy, re-stenosis) including individual interdisciplinary discussion appears of ample importance. To date no information is available on whether patients with asymptomatic high grade carotid stenosis receiving "best medical therapy" should be considered for revascularisation in general or only in selected circumstances.

Topics: Angioplasty; Anticoagulants; Carotid Artery, External; Carotid Stenosis; Endarterectomy, Carotid; Fondaparinux; Humans; Multicenter Studies as Topic; Myocardial Infarction; Polysaccharides; Prospective Studies; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Factors; Stents; Stockings, Compression; Stroke; Survival Rate; Venous Thrombosis

Aspirin is one of the pharmacological agents used for thromboprophylaxis.. National thromboprophylaxis guidelines, peer-reviewed studies and data from national joint register of England and Wales were analysed for evidence regarding the efficacy of aspirin versus other agents in thromboprophylaxis and the recommendations of guidelines.. Two of five guidelines reviewed recommend the use of aspirin for thromboprophylaxis. Aspirin is used as thromboprophylactic agent in approximately 25% of patients undergoing total hip and total knee arthroplasty in year 2006 in England and Wales. There is no difference in mortality in these patients compared to patients on other pharmacological agents.. There is conflicting evidence and differences in interpretation of the data from the literature. If specific outcome measures and complications such as symptomatic DVT, PE and bleeding were logged in arthroplasty registers, the resulting data would be useful in individualised decision-making.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Lower Extremity; Polysaccharides; Practice Guidelines as Topic; Pulmonary Embolism; Venous Thrombosis

In the last decade, parenteral anticoagulants have proven to be effective in the prevention of venous thromboembolism (VTE) in patients admitted to hospitals. Despite this, some registry studies have shown that pharmacological prophylaxis is still widely underused. We performed a literature search to identify important knowledge gaps in the use of VTE prophylaxis that were not addressed by previous published reports. MEDLINE and HighWire databases covering the years 1999-2009 were searched; only clinical trials of unselected adult subjects were included. Two reviewers independently selected studies and extracted data on inclusion and exclusion criteria, age, weight, comorbidities, study designs, and endpoints. Five of 113 relevant studies were identified from the literature search. Knowledge gaps were disclosed in subject inclusion, exclusion, and stratification regarding young age, under- and overweight, comorbidities, and the selection of clinically significant endpoints. Uncertainties in the dosage, risk stratification of subjects, and effect on hard endpoints as prevention of pulmonary embolism or reduction of mortality reduce the impact of VTE prevention clinical trials.

Topics: Anticoagulants; Drug Administration Schedule; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Infusions, Parenteral; Polysaccharides; Pulmonary Embolism; Venous Thromboembolism

Topics: Acute Disease; Algorithms; Anticoagulants; Echocardiography, Transesophageal; Fibrin Fibrinogen Degradation Products; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Risk Assessment; Tomography, X-Ray Computed; Vitamin K

The clinical presentation of pulmonary embolism (PE) varies widely, ranging from only limited symptoms to severe cardiogenic shock. Treatment of PE comprises initial therapy--with low-molecular-weight heparin (LMWH), fondaparinux, or unfractionated heparin--and long-term treatment, most commonly with vitamin-K antagonists (VKAs). Methods of risk stratification, to determine whether a patient will benefit from thrombolysis, are currently under investigation. However, at present, insufficient evidence exists that hemodynamically stable patients who demonstrate echocardiographic right ventricular strain (submassive PE) benefit from thrombolysis. By contrast, thrombolysis is a widely accepted treatment strategy for patients with hemodynamic shock (massive PE). The duration of VKA treatment is commonly 3-12 months and depends on the type of PE and on the balance between the risks of recurrent PE, major bleeding, and the patient's preference. In patients with a malignancy, treatment with LMWH during the first 6 months after diagnosis of PE is recommended. Several new oral anticoagulants, such as factor IIa and factor Xa inhibitors, are now being investigated. For prevention of recurrent PE in situations where anticoagulation is contraindicated, a temporary inferior vena cava filter might be useful. Some patients with PE can be safely treated at home, but few outcome studies in this setting have been published.

Topics: Acute Disease; Anticoagulants; Biomarkers; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Prothrombin; Pulmonary Embolism; Risk Assessment; Shock, Cardiogenic; Vitamin K

The treatment of choice for acute venous thromboembolism is anticoagulant therapy with fast-acting drugs (unfractionated or low-molecular-weight heparin or fondaparinux) aimed at preventing thrombus extension, followed by extended prophylaxis with vitamin K antagonists aimed at preventing recurrence. Experience accumulated over the years has demonstrated that strict laboratory monitoring is required for unfractionated heparin and vitamin K antagonists, making use of these drugs problematic for patients and physicians and prompting researchers to develop new anticoagulants equally effective but without the requirement for laboratory monitoring. The results of clinical trials to date, albeit limited, suggest that these new drugs will probably keep their promise. However, the definitive answer will come subsequent to these clinical trials, when clinicians will start to use these drugs to treat patients in the real world. It is likely that some sort of laboratory monitoring will be required at least for selected categories of patients. Accordingly, clinical laboratories should still be prepared to monitor patients, although the numbers may hopefully decrease sharply in the next decade or so.

Topics: Anticoagulants; Blood Coagulation; Clinical Trials as Topic; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Incidence; International Normalized Ratio; Monitoring, Physiologic; Morpholines; Polysaccharides; Prothrombin Time; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; Vitamin K

In trauma patients, pulmonary embolism occurs in up to 4% of cases and carries a mortality of 20-50%. The incidence of deep vein thrombosis (DVT) varies from 5 to 63% depending on patients' risk factors, modality of prophylaxis, and methods of detection. For these reasons, trauma patients require adequate DVT prophylaxis.. Spinal fracture or cord injury patients are at particular risk. Increasing injury severity, head injury, older age, lower limb injuries, and obesity are other risk factors. The current standard of care for DVT prophylaxis is enoxaparin (a low molecular weight heparin) as long as anticoagulation is not contraindicated. Unfractionated heparin alone does not provide sufficient protection against DVT. Selective factor Xa inhibitors such as fondaparinux are showing promising results. Other strategies for pulmonary embolism prevention include: graduated compression stockings, sequential compression devices, continuous passive motion, and prophylactic inferior vena cava filter. There is lack of consensus regarding the optimal DVT prophylaxis in trauma patients and few level I recommendations exist.. Best practice in thromboprophylaxis for trauma patients will remain on the basis of recommendations until definitive risk-benefit ratios are determined to justify the use of various mechanical and pharmacological measures, in combination or alone.

Topics: Anticoagulants; Critical Illness; Enoxaparin; Factor Xa Inhibitors; Fondaparinux; Humans; Incidence; Polysaccharides; Pulmonary Embolism; Risk Factors; Time Factors; Venous Thrombosis; Wounds and Injuries

Venous thromboembolism (VTE) is a common, severe and preventable disease. The severity of this entity ranges from isolated symptoms of deep vein thrombosis with favorable resolution to severe pulmonary embolism, with a high mortality rate. Several observational studies have reported the risk factors associated with VTE, such as prior surgery or trauma. However, non-traumatic or surgical immobility has also been demonstrated to be an important risk factor for VTE, even after short periods of time, and particularly for VTE associated with certain diseases.

Topics: Age Factors; Aged; Anticoagulants; Dalteparin; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Home Care Services; Hospitalization; Humans; Immobilization; Male; Middle Aged; Polysaccharides; Prevalence; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Venous Thromboembolism; Venous Thrombosis

The overall thromboembolic risk is the resultant of patient-related risk and surgical risk. The surgical risk is decreasing, especially with the introduction of new procedures (fast-track surgery). The value of prophylaxis has been firmly established. Mechanical prophylaxis is to be used as first-line prophylaxis when there is a risk of bleeding. Combining this with drugs increases the antithrombotic efficacy. However, the effectiveness of prophylaxis on pulmonary embolism and mortality has not been demonstrated. Renal function needs to be evaluated when low molecular weight heparins, fondaparinux, rivaroxaban or dabigatran are prescribed. An age of over 75 years and low body weight (<50 kg) have to be taken into account. There is a risk of spinal or epidural hematoma in patients receiving anticoagulants. Caution should be taken especially when administering the newer agents. Patients undergoing surgery that involves a moderate or high overall risk should receive prophylaxis until full mobilization. Patients who have undergone a total hip replacement, surgery for hip fracture, or major abdominal surgery should receive prophylaxis for about 5 weeks longer. The relevance of distal vein thromboses is debated. Surrogate venographic end-points should be gradually replaced by a combination of ultrasound and clinical criteria. The new antithrombotic agents will probably modify prevention in the years to come but currently there are very few long-term data for these products for which - it should be reminded - no antagonists are available.

Topics: Adult; Aged; Anticoagulants; Combined Modality Therapy; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Morpholines; Polysaccharides; Postoperative Complications; Preanesthetic Medication; Pulmonary Embolism; Risk Factors; Rivaroxaban; Stockings, Compression; Thiophenes; Thromboembolism; Thrombophlebitis; Vitamin K

Anticoagulation for thromboprophylaxis after THA and TKA has not been confirmed to diminish all-cause mortality. We determined whether the incidence of all-cause mortality and pulmonary embolism in patients undergoing total joint arthroplasty differs with currently used thromboprophylaxis protocols. We reviewed articles published from 1998 to 2007 that included 6-week or 3-month incidence of all-cause mortality and symptomatic, nonfatal pulmonary embolism. Twenty studies included reported 15,839 patients receiving low-molecular-weight heparin, ximelagatran, fondaparinux, or rivaroxaban (Group A); 7193 receiving regional anesthesia, pneumatic compression, and aspirin (Group B); and 5006 receiving warfarin (Group C). All-cause mortality was higher in Group A than in Group B (0.41% versus 0.19%) and the incidence of clinical nonfatal pulmonary embolus was higher in Group A than in Group B (0.60% versus 0.35%). The incidences of all-cause mortality and nonfatal pulmonary embolism in Group C were similar to those in Group A (0.4 and 0.52, respectively). Clinical pulmonary embolus occurs despite the use of anticoagulants. Group A anticoagulants were associated with the highest all-cause mortality of the three modalities studied.

Topics: Anesthesia, Conduction; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Azetidines; Benzylamines; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Intermittent Pneumatic Compression Devices; Morpholines; Platelet Aggregation Inhibitors; Polysaccharides; Pulmonary Embolism; Risk Assessment; Risk Factors; Rivaroxaban; Thiophenes; Treatment Outcome; Warfarin

Venous thrombosis is a common disease. As the mean age of the population increases, so does the incidence of venous thromboembolism. Anticoagulant therapy is equally effective in young and older patients, and can reduce substantially the associated morbidity and mortality. When considering long-term oral anticoagulant therapy in older patients, however, careful ongoing evaluation is imperative to ensure that the risk of bleeding does not outweigh the antithrombotic benefits.

Topics: Anticoagulants; Antithrombin III; Enoxaparin; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Stockings, Compression; Thrombolytic Therapy; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Chemoprevention; Combined Modality Therapy; Fondaparinux; Heparin; Hospitalization; Humans; Male; Middle Aged; Polysaccharides; Practice Guidelines as Topic; Pulmonary Embolism; Risk Assessment; Thromboembolism; Venous Thrombosis; Walking

The long-term complications of deep vein thrombosis (DVT), assessment of risk for venous thromboembolism (VTE) in medical and surgical patients, recommendations in evidence-based guidelines for VTE prophylaxis in surgical and medical patients and the treatment of VTE, and a new alternative for VTE prophylaxis and treatment are discussed.. Pulmonary embolism (PE) is an acute complication of DVT, and recurrent DVT, post-thrombotic syndrome, and death are long-term complications of DVT. The need to assess VTE risk and provide VTE prophylaxis are well recognized in surgical patients. However, VTE prophylaxis is underutilized in medical patients despite the fact that DVT is common and guidelines for prophylaxis are available, partly because the condition often is asymptomatic in these patients. The risk for VTE increases as the number of risk factors increases, so the aggressiveness of VTE prophylaxis in medical and surgical patients increases as the risk of VTE increases. The most recent American College of Chest Physicians (ACCP) guidelines recommend low-dose unfractionated heparin or low-molecular-weight heparin (LMWH) for VTE prophylaxis in acutely ill medical patients. The treatment of VTE recommended by ACCP involves short-term LMWH or unfractionated heparin therapy plus long-term oral warfarin therapy. The pentasaccharide, factor Xa inhibitor, fondaparinux is a new alternative for VTE prophylaxis and treatment. Reducing LMWH doses for patients with severe renal impairment may offer a safety advantage. Fixed doses of LMWH are customarily used for VTE prophylaxis regardless of body weight or body mass index, but weight-based dosing with larger doses for obese patients may be more effective than fixed doses.. Efforts to assess VTE risk and apply evidence-based guidelines for VTE prophylaxis and treatment in medical patients as well as surgical patients can improve patient care and outcomes. Findings from recent clinical research provide clinicians with clarification about the optimal prophylactic and treatment strategies, and future guidelines will reflect these findings.

Topics: Adult; Aged; Anticoagulants; Clinical Protocols; Drug Therapy, Combination; Evidence-Based Medicine; Female; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Outcome Assessment, Health Care; Polysaccharides; Pulmonary Embolism; Risk; Thromboembolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Fondaparinux; Forecasting; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Risk Factors; Thromboembolism; Thrombolytic Therapy; Venous Thrombosis; Vitamin K

Antithrombotic medication can be performed by means of heparins (non-fractionated heparin, low molecular heparins) or the pentasaccharide Fondaparinux as well as with oral vitamin K antagonists. The use of a low molecular heparin is initially recommended for the sake of practicability and safety in case of patients suffering from deep venous thrombosis of the leg and pelvis with subsequent long-term oral medication using a vitamin K antagonist (Marcumar) for anticoagulation. The most frequent indications for long-term anticoagulation are deep leg and pelvis thromboses, pulmonary embolism with atrial fibrillation, artificial prosthetic valves and open oval foramen with ischaemic cerebral infarction. In case of patients with chronic atrial fibrillation it is expedient to initiate permanent anticoagulation according to a risk score. For the purpose of controlling oral anticoagulation it is recommended to employ the INR value in place of Quick's value because these data are better comparable. In case of atherothrombotic diseases secondary prevention will always indicate administration of a thrombocyte aggregation inhibitor. In such cases acetylsalicylic acid is recommended as the standard preparation.

Topics: Administration, Oral; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atherosclerosis; Atrial Fibrillation; Blood Coagulation Tests; Cerebral Infarction; Drug Therapy, Combination; Female; Fibrinolytic Agents; Fondaparinux; Heart Valve Prosthesis; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Polysaccharides; Preoperative Care; Prevalence; Primary Prevention; Pulmonary Embolism; Risk Factors; Sex Factors; Stroke; Time Factors; Venous Thrombosis

This article summarizes the published data on the prevention of venous thromboembolism. Routine thromboprophylaxis is the best way to lower the risk. It is recommended to sort patients according the thrombosis risk and to make use of the standard prophylactic modes. In low risk patients, no specific thromboprophylaxis is needed. Patients with moderate risk levels are candidates for administration of subcutaneous low molecular weight heparin (LMWH) at doses under 3 400 anti-Xa units a day and patients with increased risk at doses higher than 3400 anti-Xa units a day during the period of higher risk. In order to decrease the risk of bleeding, a half dose 2 hours prior or 4-6 hours after the operation can be administered. Under the highest risk conditions, there is a recommendation to combine LMWH over 3 400 anti-Xa units with elastic panty-hose or, alternatively, with intermittent pneumatic compression. At moderate risk levels, subcutaneous administration of unfractionated heparin at the doses of 5 000 units twice a day is also possible and at increased risk levels, a TID administration over the increased risk period. In patients with a significant bleeding risk, the physical method of thromboprophylaxis can be used and pharmacological prophylaxis can set in after the risk of bleeding has passed. Fondaparinux is the alternative to LMWH in people after major orthopaedic surgeries and with a history of heparin induced thrombocytopenia over the past three months. An alternative to the administration of LMWH even after the end of the hospitalization can be warfarin in certain situations. The sole use of acetylsalicylic acid or Rheodextran is not recommended. While undertaking epidural anaesthesia or analgesia, it is necessary to follow strictly the guidelines of the use of pharmacological thromboprophylaxis.

Topics: Anticoagulants; Bandages; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Intermittent Pneumatic Compression Devices; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Risk Factors; Thromboembolism; Venous Thrombosis

Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into two stages. Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists, such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This paper i) reviews the pharmacology of these agents, ii) outlines their potential strengths and weaknesses, iii) describes the results of clinical trials with these new drugs, and iv) identifies the evolving role of new anticoagulants in the management of VTE.

Topics: Anticoagulants; Fondaparinux; Glycosaminoglycans; Heparin, Low-Molecular-Weight; Humans; Models, Chemical; Oligosaccharides; Polysaccharides; Postphlebitic Syndrome; Pulmonary Embolism; Thromboembolism; Venous Thrombosis; Vitamin K; Warfarin

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Azetidines; Benzylamines; Clinical Trials, Phase III as Topic; Fibrinolytic Agents; Fondaparinux; Glycine; Humans; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Thromboembolism; Venous Thrombosis

Autopsies and clinical studies have shown that venous thromboembolism (VTE) is a common cause of morbidity and mortality in medical patients. Prophylaxis of VTE has been less extensively studied in medical patients than in surgical patients, and the results of recent practice audits indicate that the use of thromboprophylaxis is uncommon in medical patients. In the past few years, 3 large randomized clinical trials have demonstrated the efficacy and safety of prophylaxis of VTE in the medical setting. The prophylaxis in MEDical patients with ENOXaparin (MEDENOX), Prospective Evaluation of Dalteparin Efficacy for PREVENTion of VTE in Immobilized Patients Trial (PREVENT), and ARixta for ThromboEmbolism Prevention in a Medical Indications Study (ARTEMIS) studies have compared the low-molecular-weight heparins enoxaparin and dalteparin, and the specific factor Xa inhibitor fondaparinux, respectively, with placebo in acutely ill medical patients hospitalized with heart failure, respiratory failure, infectious disease, or inflammatory disease. All studies showed both a statistically significant reduction in the rate of venous thromboembolic events (as assessed by venography or compression ultrasonography) and a rate of major bleeding events that were comparable to placebo. The results of these studies support the evidence-based recommendations for systematic use of thromboprophylaxis in this setting.

Topics: Aged; Anticoagulants; Dalteparin; Enoxaparin; Fondaparinux; Humans; Middle Aged; Polysaccharides; Pulmonary Embolism; Randomized Controlled Trials as Topic; Thromboembolism; Venous Thrombosis

Treatment of venous thromboembolism (VTE) has evolved significantly over the last decade. Low-molecular-weight heparins have largely replaced unfractionated heparin in the treatment of deep-vein thrombosis (DVT) but the majority of patients with pulmonary embolism (PE) continue to be treated with unfractionated heparin. Fondaparinux is the first synthetic selective inhibitor of factor Xa. It has recently been proved to be more effective than, and as safe as, a low-molecular-weight heparin for the prevention of VTE after major orthopaedic surgery. The two large randomised MATISSE trials demonstrated that fondaparinux was at least as effective and as safe as previous reference heparin therapies in the treatment of VTE. Fondaparinux should further simplify the treatment of this frequent disease since a single once-daily fixed dosage regimen may effectively and safely treat both DVT and PE, an important point especially considering the frequent though clinically silent concomitance of these two thrombotic events.

Topics: Anticoagulants; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Venous Thrombosis

Anticoagulation is an essential component of the care of patients with venous thromboembolism (VTE). Traditional anticoagulants for the treatment of VTE include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and the oral vitamin K antagonist, warfarin. A variety of anticoagulant agents with improved pharmacologic and clinical profiles are emerging and offer benefits over the traditional therapies. One of the most recent advances has been the development of new agents, such as oral direct thrombin inhibitors and factor Xa inhibitors, that have a more selective and targeted effect on the coagulation cascade. Recent clinical trials have evaluated fondaparinux, the first commercially available factor Xa inhibitor, in the treatment of patients with deep vein thrombosis and pulmonary embolism and indicate efficacy and safety as compared with traditional options such as UFH and LMWH. Fondaparinux is a welcomed addition to the available antithrombotic options.

Topics: Anticoagulants; Antithrombin III; Clinical Trials as Topic; Fondaparinux; Humans; Polysaccharides; Pulmonary Embolism; Thromboembolism; Venous Thrombosis

Venous thromboembolism VTE remains a common but preventable disease. The last decade has witnessed major advances in VTE treatment and prophylaxis. Low molecular weight heparins LMWH became the agents of choice in the treatment of deep venous thrombosis DVT and are increasingly used in the treatment of stable pulmonary embolism PE. Increasing focus on simplicity and efficacy has led to the discovery of the synthetic pentasaccharides, substances that specifically inhibit factor Xa activity, producing an antithrombotic effect without affecting other coagulation factors or platelets. Fondaparinux, the first pentasaccharide introduced into the market, was first tried as a prophylactic agent against VTE in patients undergoing major orthopedic procedures, such as hip fracture, total hip and knee replacements, such approach appeared to be more effective than LMWH. Fondaparinux was also used, with promising results, in prophylaxis in patients undergoing major abdominal surgery and high risk medical patients. Pentasaccharides were recently tried in the treatment of both DVT and PE. The largest clinical investigation program ever undertaken in this therapeutic area, has shown that pentasaccharides are as safe and as effective as either unfractionated heparin UFH or LMWH, with the added convenience of once daily injection, no need for monitoring the anticoagulant effect and no major side effects such as thrombocytopenia. Therefore, the efficacy, the safety profile and the added convenience for both patients and physicians alike, will probably keep pentasaccharides as the front runner among new anticoagulants of the future. This article focuses on the use of fondaparinux as a prophylactic agent against VTE in patients undergoing major orthopedic and abdominal surgery along with high risk medical patients; it will also discuss the recent promising data on its use to treat active DVT and PE.

Topics: Anticoagulants; Enoxaparin; Female; Fondaparinux; Humans; Male; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Sensitivity and Specificity; Thromboembolism

Treatment of venous thromboembolism (VTE) usually starts with concomitant administration of heparin or low-molecular-weight heparin (LMWH) and a vitamin K antagonist. The parenteral anticoagulant, which is given for at least 5 days, is stopped once the vitamin K antagonist produces a therapeutic level of anticoagulation. Although the introduction of LMWH has simplified the initial treatment of VTE, problems remain. LMWH must be given by daily subcutaneous (SC) injection and vitamin K antagonists require routine coagulation monitoring, which is inconvenient for patients and physicians. Recently, 3 new anticoagulants have been introduced in an attempt to overcome these limitations. These include fondaparinux and idraparinux, synthetic analogs of the pentasaccharide sequence that mediates the interaction of heparin and LMWH with antithrombin, and ximelagatran, an orally active inhibitor of thrombin. These agents produce a predictable anticoagulant response; thus, routine coagulation monitoring is unnecessary. Because they do not bind to platelets or platelet factor 4, fondaparinux and idraparinux do not cause heparin-induced thrombocytopenia (HIT). Unlike vitamin K antagonists, ximelagatran has a rapid onset of action, thereby obviating the need for concomitant administration of a parenteral anticoagulant when starting treatment. The lack of an antidote for these new agents is a drawback, particularly for idraparinux, which has a long half-life.

Topics: Anticoagulants; Azetidines; Benzylamines; Clinical Trials as Topic; Fondaparinux; Humans; Oligosaccharides; Polysaccharides; Pulmonary Embolism; Thromboembolism; Venous Thrombosis

This article discusses the prevention of venous thromboembolism (VTE) and is part of the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following. We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A). For moderate-risk general surgery patients, we recommend prophylaxis with low-dose unfractionated heparin (LDUH) (5,000 U bid) or low-molecular-weight heparin (LMWH) [< or = 3,400 U once daily] (both Grade 1A). For higher risk general surgery patients, we recommend thromboprophylaxis with LDUH (5,000 U tid) or LMWH (> 3,400 U daily) [both Grade 1A]. For high-risk general surgery patients with multiple risk factors, we recommend combining pharmacologic methods (LDUH three times daily or LMWH, > 3,400 U daily) with the use of graduated compression stockings and/or intermittent pneumatic compression devices (Grade 1C+). We recommend that thromboprophylaxis be used in all patients undergoing major gynecologic surgery (Grade 1A) or major, open urologic procedures, and we recommend prophylaxis with LDUH two times or three times daily (Grade 1A). For patients undergoing elective total hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or adjusted-dose vitamin K antagonist (VKA) [international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0] (all Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1C+), VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 2B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty, or HFS receive thromboprophylaxis for at least 10 days (Grade 1A). We recommend that all trauma patients with at least one risk factor for VTE receive thromboprophylaxis (Grade 1A). In acutely ill medical patients who have been admitted to the hospital with congestive heart failure or severe respiratory disease, or who are confined to bed and have one or more additional risk factors, we recommend prophylaxis with LDUH (Grade 1A) or LMWH

Topics: Anticoagulants; Aspirin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Evidence-Based Medicine; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Randomized Controlled Trials as Topic; Risk Assessment; Venous Thrombosis; Vitamin K

Every year, approximately 2 million people experience a deep venous thrombosis (DVT). Approximately 600,000 of these people are diagnosed with a pulmonary embolism and about 10% of these die. It has been established that surgery, anesthesia, and bed rest increase the risk of DVT, and therefore, patients who undergo a major lower-extremity procedure should receive prophylaxis. During the past 10 years, the choices of pharmacological and mechanical prophylaxis have increased greatly. Warfarin is probably the most widely used prophylactic method in the U.S., but low-molecular-weight heparin (LMWH) use has increased. Also available is a synthetic pentasaccharide that acts as an anti-Xa inhibitor to decrease DVT without increase in bleeding. All but warfarin are given by subcutaneous injection and require no laboratory management to adjust the medication. Another drug in clinical trials is a direct thrombin inhibitor taken orally in a fixed dose that does not require monitoring. Non-pharmacological prophylaxis and/or stacked modalities, although used, have not shown the efficacy of pharmacological prophylaxis. With the incidence of DVT reported in the range of 41% to 85% without prophylaxis in joint replacement and hip-fracture surgery, prophylaxis is warranted in all lower-extremity joint replacement and hip-fracture patients.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Azetidines; Benzylamines; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Venous Thrombosis; Warfarin

The current management of thrombotic and vascular disorders has been strongly influenced by the introduction of several new drugs. 1. One of the major impact in the management of venous thromboembolic disorders has been the LMWHs. The newest, third generation heparin, the pentasaccharide inhibits specifically FXa. The elimination half-life of pentasaccharide is about 17 h, which allows a convenient once-daily dosing regime. The effects of pentasaccharide needs antithrombin. 2. Melagatran dipeptid is a specific, reversible direct thrombin inhibitor. It inhibits free and clot bound thrombin. Ximelagatran is a prodrug of melagatran. It is the first clinically used orally acting direct thrombin inhibitor. 3. Recombinant human activated protein C (rh-APC) has some advantages in patients with septic DIC. Qualities of the three new anticoagulants and clinical experiences with them have been summarized.

Topics: Anticoagulants; Azetidines; Benzylamines; Fondaparinux; Glycine; Humans; Polysaccharides; Protein C; Pulmonary Embolism; Recombinant Proteins; Venous Thrombosis

Unfractionated heparin, low molecular weight heparin and vitamin K antagonists are anticoagulants currently used for the prevention and treatment of deep vein thrombosis and pulmonary embolism. Considerable limitations of these agents, such as a narrow therapeutic window, a variable dose response or lack of oral bioavailability, created the need for new anticoagulants. Numerous new compounds with different mechanisms of action have been developed and some have been already approved for clinical use. Quite recently, fondaparinux, an indirect anti-factor Xa inhibitor, has been licensed in Europe and in the US for prevention of VTE in patients undergoing hip or knee replacement surgery. In addition, lepirudin, a recombinant hirudin derivative, and the heparinoid danaparoid, have been approved in Austria for treatment of heparin-induced thrombocytopenia. Recombinant nematode anticoagulant protein c2, the orally available thrombin inhibitor ximelagatran and ART-123, a recombinant soluble thrombomodulin, are in advanced stages of clinical development. This article reviews mechanisms and sites of action, and the current state of preclinical and clinical research of these and various other agents with respect to the prevention and treatment of venous thromboembolism).

Topics: Anticoagulants; Azetidines; Benzylamines; Blood Coagulation Factors; Drugs, Investigational; Fondaparinux; Glycine; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Research; Thrombin; Venous Thrombosis; Vitamin K

Venous thromboembolism is a frequent, life-threatening, postoperative complication of hip-fracture and total-knee-replacement surgery. Fondaparinux is a synthetic polysaccharide that selectively binds to antithrombin, the primary endogenous regulator of blood coagulation. Low molecular weight heparins, such as enoxaparin, are less specific inhibitors of coagulation. In patients undergoing hip-fracture surgery, fondaparinux is more effective than once-daily enoxaparin as prophylaxis for venous thromboembolism. Fondaparinux (25 mg/day sc.) was also more effective than enoxaparin (30 mg sc. b.i.d.) as prophylaxis for venous thromboembolism in elective knee surgery. These differences may be explained by the fact that there is less prophylaxis cover with enoxaparin, as it has a much shorter duration of action than fondaparinux. Thus, with the present dosing regimens, fondaparinux is probably preferable to enoxaparin for the prevention of venous thromboembolism.

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Enoxaparin; Fondaparinux; Humans; Polysaccharides; Pulmonary Embolism; Thromboembolism; Venous Thrombosis

Antithrombotic therapy with unfractionated heparin (UFH) and warfarin for the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) became widely accepted in the early 1960s. Subsequent clinical trials have focused on the importance of early intravenous UFH in the treatment of venous thromboembolic events, the method of heparin administration, the importance of rapid anticoagulation to prevent recurrent venous thromboembolism (VTE), and the optimal duration of UFH administration. Low-molecular-weight heparin (LMWH) represents a significant advance over UFH therapy for VTE. Developed in the late 1980s, LMWH has become an excellent alternative to UFH because it offers superior efficacy and safety, improved pharmacokinetics, longer half-life, and once- or twice-daily subcutaneous administration without the need for laboratory monitoring. Fondaparinux is the first of a new class of antithrombotic agents that targets factor Xa. Based on studies of the heparin binding site of antithrombin, this novel pentasaccharide has superior pharmacokinetics and bioavailability when compared with LMWH and can be administered once daily. Studies in patients undergoing major orthopedic surgery and in those with proximal DVT indicate that the efficacy and safety of fondaparinux may represent an improvement over those of LMWH.

Topics: Double-Blind Method; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Meta-Analysis as Topic; Polysaccharides; Pulmonary Embolism; Randomized Controlled Trials as Topic; Thromboembolism; Treatment Outcome

Superficial-vein thrombosis can lead to deep-vein thrombosis and pulmonary embolism. Rivaroxaban, an oral factor Xa inhibitor, might simplify treatment compared with fondaparinux because it does not require daily subcutaneous injection and is cheaper. We compared efficacy outcomes in patients with superficial-vein thrombosis and additional risk factors given either rivaroxaban or fondaparinux to assess whether rivaroxaban is non-inferior to fondaparinux in the prevention of thromboembolic complications.. In this open-label, masked endpoint, randomised, non-inferiority phase 3b trial, we recruited patients aged 18 years or older with symptomatic superficial-vein thrombosis from 27 sites (academic, community hospitals, and specialist practices) in Germany. We randomly assigned patients (1:1) to receive 10 mg oral rivaroxaban or 2·5 mg subcutaneous fondaparinux once a day for 45 days. Patients were eligible if they had symptomatic thrombosis (at least 5 cm in a supragenual superficial-vein segment) and at least one additional risk factor (older than 65 years, male sex, previous venous thromboembolism, cancer, autoimmune disease, thrombosis of non-varicose veins). Main exclusion criteria were: symptoms for longer than 3 weeks, thrombus within 3 cm of the sapheno-femoral junction, indication for full-dose anticoagulation therapy, and substantial hepatic or renal impairment. Randomisation was done with a central block randomisation process. The primary efficacy outcome was a composite of symptomatic deep-vein thrombosis or pulmonary embolism, progression or recurrence of superficial vein-thrombosis, and all-cause mortality at 45 days in the per-protocol population (all randomly assigned patients without major protocol violations). We used a non-inferiority margin of 4·5% (absolute difference between rivaroxaban and fondaparinux). The main safety outcome was major bleeding. This study is registered with ClinicalTrials.gov, number NCT01499953.. Between April 25, 2012, and Feb 18, 2016, 485 patients were enrolled in the study and 472 were randomly assigned to the rivaroxaban group (n=236) or the fondaparinux group (n=236). In the 435 patients included in the per-protocol analysis set, the primary efficacy outcome occurred in seven (3%) of 211 patients (95% CI 1·6-6·7) in the rivaroxaban group and in four (2%) of 224 patients (0·7-4·5) in the fondaparinux group (hazard ratio [HR] 1·9, 95% CI 0·6-6·4; p=0·0025 for non-inferiority) at day 45. There were no major bleeds in either group. There was one death in the rivaroxaban group; this patient died from cardiogenic shock on day 50 after a type A aortic dissection, not related to treatment.. Rivaroxaban was non-inferior to fondaparinux for treatment of superficial-vein thrombosis in terms of symptomatic deep-vein thrombosis or pulmonary embolism, progression or recurrence of superficial vein-thrombosis, and all-cause mortality, and was not associated with more major bleeding. Therefore, rivaroxaban could offer patients with symptomatic superficial-vein thrombosis a less burdensome and less expensive oral treatment option instead of a more expensive subcutaneous injection.. GWT-TUD and Bayer Vital.

Topics: Aged; Aged, 80 and over; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Humans; Male; Middle Aged; Polysaccharides; Pulmonary Embolism; Rivaroxaban; Thrombosis; Venous Thrombosis

In cancer patients, the chest computer tomography (CT) can be used to identify asymptomatic pulmonary embolism (APE). In most cases, these patients are treated with anticoagulant drugs for at least 3 months. The American College of Physicians recommend treatment of these patients as patients with symptomatic pulmonary embolism. In this study, we evaluated and compared the efficacy and safety of fondaparinux vs warfarin in the prevention of unsuspected pulmonary embolism in patients with active cancer.. A prospective and parallel group study was performed on 64 cancer patients (29 males and 35 females) with APE. A multidetector CT angiography with high spatial and temporal resolution and quality of arterial opacification was used to make the diagnosis. Lung scintigraphy was reserved to selected patients only. Patients were randomized to either the warfarin (Group A) or the fondaparinux (Group B) for 90 days. The first end point of efficacy was the persistence, reduction, or disappearance of thrombosis after 90 days. The second end point was the reappearance of thrombosis after 1 year. The first end point of safety was the development of major bleeding.. We enrolled 32 patients into each treatment group. We reached the first end point of efficacy and safety in Group B which showed that fondaparinux was able to induce the disappearance of thrombotic pulmonary with a lower incidence of major bleeding events compared with warfarin. No difference in the secondary end point was recorded.. We suggest that the treatment of cancer patients with APE can be oriented with the administration of a standard dose of fondaparinux until the next CT lung control (3 months). However, the lack of a randomized clinical trial, including a larger patient cohort, does not allow formulation of final recommendations in these patients. A broader study would be desirable, involving a larger number of patients and a longer follow-up period.

Topics: Anticoagulants; Antineoplastic Agents; Female; Fondaparinux; Humans; Male; Neoplasms; Polysaccharides; Pulmonary Embolism; Warfarin

Renal impairment is common, affecting around 40% of acutely ill medical patients, and is associated with an increased risk of both venous thromboembolism (VTE) and bleeding. The clinical benefit of effective thromboprophylactic strategies may be outweighed in these patients by an excessive rate of hemorrhage.. To assess the safety and efficacy of lower prophylactic doses of fondaparinux in acutely ill medical patients with renal impairment.. We carried out a multicenter, investigator-initiated, prospective cohort study. Patients at risk of VTE with a creatinine clearance between 20 and 50 mL min(-1) were treated with fondaparinux 1.5 mg qd for a minimum of 6 to a maximum of 15 days. The primary outcome was the incidence of major bleeding; secondary outcomes were clinically relevant non-major bleeding (CRNMB) and symptomatic VTE.. We enrolled 206 patients with a mean age of 82 years, mean creatinine clearance of 33 mL min(-1) , and a mean Charlson co-morbidity index of 8.2. One patient had major bleeding (0.49%, 95% confidence interval [CI] 0.03-3.10), eight had CRNMB (3.88%, 95% CI 1.81-7.78) and three developed symptomatic VTE (1.46%, 0.38-4.55). Twenty-three patients (11.17%, 7.36-16.48) died. No independent predictors of bleeding were found at univariate analysis.. The addition of moderate to severe renal impairment to patients with traditional risk factors for VTE identified a population of very elderly acutely ill medical patients potentially at high risk of both VTE and bleeding complications. The recently approved lower prophylactic dose of fondaparinux appears to be a safe and relatively effective strategy in these patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Creatinine; Female; Fondaparinux; Hemorrhage; Humans; Incidence; Male; Middle Aged; Polysaccharides; Prospective Studies; Pulmonary Embolism; Renal Insufficiency; Risk Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Surgery for pelvic or acetabular fractures carries a high risk of deep-vein thrombosis (DVT). Reports indicate that fondaparinux is a more effective thromboprophylactic agent than low molecular weight heparin (LMWH) after major orthopaedic surgery. The safety and efficacy of fondaparinux was evaluated in a new protocol used for DVT prophylaxis. One hundred and twenty seven patients with pelvic or acetabular fractures received either fondaparinux or enoxaparin and were analysed in a historical non-concurrent study. Specific review points included clinical deep-vein thrombosis (DVT) or pulmonary embolism (PE) and evidence of adverse effects such as bleeding or allergic reactions. Two patients that received enoxaparin were found to have a DVT and one patient had a PE. There was no documented DVT or PE in patients that received fondaparinux. The mean number of units of blood transfused postoperatively was higher in the enoxaparin group; however, multivariate regression modelling demonstrated no significant difference between the groups. The most current large randomised controlled studies investigating the administration of fondaparinux following joint arthroplasty or hip fracture surgery, have demonstrated a slight increase or a similar number of bleeding events in patients treated with fondaparinux when compared to those treated with enoxaparin. The current report supports that fondaparinux, in patients with pelvic and acetabular fractures, can be equally effective as enoxaparin and not associated with adverse bleeding events.

Topics: Acetabulum; Adult; Anticoagulants; Enoxaparin; Female; Fondaparinux; Fractures, Bone; Humans; Male; Orthopedic Procedures; Pelvic Bones; Polysaccharides; Postoperative Hemorrhage; Pulmonary Embolism; Venous Thrombosis; Wounds and Injuries

Unfractionated heparin (UFH) is the standard drug for the initial treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT) in Japan, whereas fondaparinux is the standard drug in Europe and the United States. Here, we examine the efficacy and safety of fondaparinux in Japanese patients.. In 2 randomized, open-label, multicenter studies, 80 Japanese patients with acute PE or DVT received either subcutaneous fondaparinux or intravenous UFH as a non-comparative reference, in a 3:1 ratio, for 5-10 days. Concomitant warfarin therapy was continued until Day 90. Multidetector-row computed tomography-based assessment showed that 57.9% and 45.9% of the patients with acute PE and acute proximal DVT had proximal DVT and PE as a complication, respectively. There was no recurrence of symptomatic venous thromboembolism. In the fondaparinux group, the respective improvement rates at the end of the initial treatment and follow-up periods were 71.4% and 86.8% for 42 patients with PE, and 57.8% and 83.3% for 46 patients with DVT; similar results were noted in the UFH group. One patient in the fondaparinux group experienced major bleeding during the initial treatment, but no such episode in the UFH group.. Once-daily, subcutaneous fondaparinux is as effective and safe without monitoring as adjusted-dose intravenous UFH for the initial treatment of acute PE and DVT in Japanese patients.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anticoagulants; Asian People; Contrast Media; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Infusions, Intravenous; Injections, Subcutaneous; Japan; Male; Middle Aged; Polysaccharides; Predictive Value of Tests; Pulmonary Embolism; Recurrence; Risk Assessment; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Warfarin; Young Adult

The efficacy of measuring anti-Xa activity was evaluated in major orthopedic surgery patients receiving thrombo-prophylaxis with Fondaparinux. Although 98 orthopedic patients including those receiving total hip replacement (THR) and total knee replacement (TKR) were treated with 1.5 mg of Fondaparinux for prophylaxis of deep vein thrombosis (DVT). Sixteen patients developed DVT, but none was associated with a fatal pulmonary embolism. There was a wide range of anti-Xa activity, but there were no patients with less than 0.15 mg/l or more than 0.90 mg/l. Anti-Xa activity gradually increased from days 1 to 8 and showed no significant difference between patients with and without DVT. Anti-Xa activity was correlated with weight, height, body mass index, and antithrombin activity. Postoperative plasma levels of D: -dimer and soluble fibrin (SF) were markedly high, and those were significantly reduced at days 1 and 4 of treatment with Fondaparinux. Plasma levels of SF were significantly reduced at days 8 and 15, but D: -dimer was not. These findings suggested that there was continued thrombin generation after the injection of Fondaparinux until day 8 and secondary fibrinolysis occurred on day 8. In conclusion, 1.5 mg of Fondaparinux may not be sufficient for the prophylaxis of silent DVT, but it was found to be useful for that of fatal pulmonary embolism. Consequently, monitoring anti-Xa activity may be unnecessary for the administration of Fondaparinux at such doses.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement; Biomarkers; Chemoprevention; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Middle Aged; Polysaccharides; Premedication; Pulmonary Embolism; Treatment Outcome; Venous Thrombosis

To determine the incidence and causes of skin reactions to the synthetic pentasaccharide fondaparinux.. Patients who received prophylactic/therapeutic subcutaneous fondaparinux treatment for more than 7 days were prospectively examined for cutaneous adverse effects between September 1, 2008, and April 30, 2009. When indicated, other procedures, such as skin biopsy, allergy testing, and clinical/laboratory assessment for thrombosis and heparin-induced thrombocytopenia, were performed.. Overall, 231 patients were enrolled. No patient developed typical delayed type IV hypersensitivity (DTH) erythematous skin lesions. However, one female patient experienced abdominal pruritus at sites of injection. Histology revealed a mild lymphohistiocytic infiltrate, confirming a DTH reaction. Heparin-induced thrombocytopenia, as another possible underlying pathomechanism for cutaneous lesions, was ruled out clinically and serologically. Hence, the overall incidence of fondaparinux-induced allergic skin lesions was 0.4% (95% confidence interval, 0.01%-2.4%). No cross-allergies were observed in patients with DTH reaction to heparins.. Fondaparinux has a low allergenic potential. The incidence of allergic cutaneous DTH reactions is almost 20 times lower compared to that with commonly used heparins. These results, together with the known low prevalence of secondary thrombotic events or heparin-induced thrombocytopenia during fondaparinux therapy, suggest that in selected patients fondaparinux might substantially improve patient care, therapeutic safety, and cost-effectiveness of anticoagulant therapy.. clinicaltrials.gov identifier: NCT00510432.

Topics: Anticoagulants; Biopsy; Dose-Response Relationship, Drug; Drug Hypersensitivity; Factor X; Female; Follow-Up Studies; Fondaparinux; Germany; Humans; Incidence; Injections, Subcutaneous; Male; Middle Aged; Nadroparin; Polysaccharides; Prognosis; Prospective Studies; Pulmonary Embolism; Severity of Illness Index; Skin; Skin Tests

The efficacy and safety of anticoagulant treatment for patients with acute, symptomatic superficial-vein thrombosis in the legs, but without concomitant deep-vein thrombosis or symptomatic pulmonary embolism at presentation, have not been established.. In a randomized, double-blind trial, we assigned 3002 patients to receive either fondaparinux, administered subcutaneously at a dose of 2.5 mg once daily, or placebo for 45 days. The primary efficacy outcome was a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep-vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of superficial-vein thrombosis at day 47. The main safety outcome was major bleeding. The patients were followed until day 77.. The primary efficacy outcome occurred in 13 of 1502 patients (0.9%) in the fondaparinux group and 88 of 1500 patients (5.9%) in the placebo group (relative risk reduction with fondaparinux, 85%; 95% confidence interval [CI], 74 to 92; P<0.001). The incidence of each component of the primary efficacy outcome was significantly reduced in the fondaparinux group as compared with the placebo group, except for the outcome of death (0.1% in both groups). The rate of pulmonary embolism or deep-vein thrombosis was 85% lower in the fondaparinux group than in the placebo group (0.2% vs. 1.3%; 95% CI, 50 to 95; P<0.001). Similar risk reductions were observed at day 77. A total of 88 patients would need to be treated to prevent one instance of pulmonary embolism or deep-vein thrombosis. Major bleeding occurred in one patient in each group. The incidence of serious adverse events was 0.7% with fondaparinux and 1.1% with placebo.. Fondaparinux at a dose of 2.5 mg once a day for 45 days was effective in the treatment of patients with acute, symptomatic superficial-vein thrombosis of the legs and did not have serious side effects. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00443053.)

Topics: Acute Disease; Anticoagulants; Double-Blind Method; Female; Fondaparinux; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Polysaccharides; Pulmonary Embolism; Recurrence; Risk; Treatment Outcome; Venous Thrombosis

No data are available on the efficacy and safety of a combination of fondaparinux and thrombolysis in the setting of high to intermediate risk pulmonary embolism (PE). Patients submitted to thrombolysis and fondaparinux, presenting with > or =1 of the following criteria were included: (1) cardiogenic shock, (2) syncope, (3) > or =1 proximal thrombo-embolus at CT scan, (4) positive troponin test, (5) echocardiographic findings indicating right ventricular (RV) dysfunction. In-hospital results included death, recurrent PE, persistent RV dysfunction at 48 h echocardiography, bleeding complications. Twenty seven patients were included; 22 received a 2 h infusion of rt-PA and 5 received a 2 h infusion of streptokinase. Ten patients presented with cardiogenic shock (37%), 8 with syncope (30%), all had RV dysfunction. 82% of patients had an uneventful in-hospital course. One patient died during hospital stay from refractory shock. Thrombolysis failed in 2 patients (7%), requiring successful rescue surgical embolectomy. Bleeding events occurred in 2 patients (7%), of whom 1 required blood transfusion. Despite the small sample size, our data suggest that fondaparinux procures adequate tolerability compared to standard current therapy in combination with thrombolysis in high to intermediate risk PE.

Topics: Aged; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug-Related Side Effects and Adverse Reactions; Female; Fondaparinux; Hemorrhage; Humans; Male; Middle Aged; Phenindione; Polysaccharides; Pulmonary Embolism; Risk; Streptokinase; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome

Venous thromboembolic events (VTE) remain a major cause of morbidity and mortality after trauma. Fondaparinux, a synthetic, nonheparin drug, has shown promise in reducing VTE in orthopaedic patients, but has not previously been studied in trauma patients. The goal of this study was to determine the safety and efficacy of fondaparinux when incorporated into our VTE prevention protocol. We hypothesized that the occult deep vein thrombosis (DVT) rate in high-risk patients receiving fondaparinux would be <5%.. Consented patients were assigned to a treatment group stratified by their VTE risk factors: high-risk, fondaparinux 2.5 mg subcutaneously once daily; very high-risk, both fondaparinux and pneumatic compression. Patients who were not candidates for anticoagulation received pneumatic compression only. All patients underwent surveillance venous ultrasonography imaging of upper and lower extremities on enrollment and weekly thereafter. Serum samples were analyzed for peak and trough drug concentration levels.. Overall incidence of DVT among the 87 enrolled patients was 4.6%. DVT developed in only 1 of 80 patients who received fondaparinux (1.2%). One patient assigned to fondaparinux had a DVT on initial scan before receiving prophylaxis. DVT developed in two of six patients in pneumatic compression only (33%). There were no episodes of pulmonary embolism, thrombocytopenia, or bleeding attributable to fondaparinux. Serum levels indicated adequate absorption of the drug and an effective dosing regimen.. Fondaparinux appears to offer protection against VTE in high-risk trauma patients. Its once-daily dosing regimen can improve compliance and reduce cost and eliminate risk of heparin-induced thrombocytopenia.

Topics: Adult; Aged; Anticoagulants; Combined Modality Therapy; Drug Administration Schedule; Female; Fondaparinux; Humans; Injections, Subcutaneous; Injury Severity Score; Intermittent Pneumatic Compression Devices; Male; Middle Aged; Pilot Projects; Polysaccharides; Pulmonary Embolism; Risk Assessment; Risk Factors; Treatment Outcome; Venous Thromboembolism; Wounds and Injuries

The benefit of thromboprophylaxis for 1 month has never been evaluated in patients undergoing hip fracture surgery, a setting in the highest risk category for postoperative venous thromboembolism (VTE).. In a double-blind multicenter trial, 656 patients undergoing hip fracture surgery were randomly assigned to receive prophylaxis with a once-daily subcutaneous injection of either 2.5 mg of fondaparinux sodium or placebo for 19 to 23 days. Before randomization, all patients had received fondaparinux for 6 to 8 days. The primary efficacy outcome was VTE occurring during the double-blind period (deep vein thrombosis detected by mandatory bilateral venography or documented symptomatic deep vein thrombosis or pulmonary embolism). The main safety outcome was major bleeding.. The primary efficacy outcome was assessed in 428 patients. Fondaparinux reduced the incidence of VTE compared with placebo from 35.0% (77/220) to 1.4% (3/208), with a relative reduction in risk of 95.9% (95% confidence interval, 87.2%-99.7%; P<.001). Similarly, the incidence of symptomatic VTE was significantly lower with fondaparinux (1/326; 0.3%) than with placebo (9/330; 2.7%). The relative reduction in risk was 88.8% (P =.02). Although there was a trend toward more major bleeding in the fondaparinux group than in the placebo group (P =.06), there were no differences between the 2 groups in the incidence of clinically relevant bleeding (leading to death, reoperation, or critical organ bleeding).. Extended prophylaxis with fondaparinux for 3 weeks after hip fracture surgery reduced the risk of VTE by 96% and was well tolerated.

Topics: Adult; Aged; Aged, 80 and over; Double-Blind Method; Drug Administration Schedule; Female; Fibrinolytic Agents; Fondaparinux; Hip Fractures; Humans; Injections, Subcutaneous; Male; Middle Aged; Polysaccharides; Postoperative Complications; Prospective Studies; Pulmonary Embolism; Venous Thrombosis

The standard initial treatment of hemodynamically stable patients with pulmonary embolism is intravenous unfractionated heparin, requiring laboratory monitoring and hospitalization.. We conducted a randomized, open-label trial involving 2213 patients with acute symptomatic pulmonary embolism to compare the efficacy and safety of the synthetic antithrombotic agent fondaparinux with those of unfractionated heparin and to document noninferiority in terms of efficacy. Patients received either fondaparinux (5.0, 7.5, or 10.0 mg in patients weighing less than 50, 50 to 100, or more than 100 kg, respectively) subcutaneously once daily or a continuous intravenous infusion of unfractionated heparin (ratio of the activated partial-thromboplastin time to a control value, 1.5 to 2.5), both given for at least five days and until the use of vitamin K antagonists resulted in an international normalized ratio above 2.0. The primary efficacy outcome was the three-month incidence of the composite end point of symptomatic, recurrent pulmonary embolism (nonfatal or fatal) and new or recurrent deep-vein thrombosis.. Forty-two of the 1103 patients randomly assigned to receive fondaparinux (3.8 percent) had recurrent thromboembolic events, as compared with 56 of the 1110 patients randomly assigned to receive unfractionated heparin (5.0 percent), for an absolute difference of -1.2 percent in favor of fondaparinux (95 percent confidence interval, -3.0 to 0.5). Major bleeding occurred in 1.3 percent of the patients treated with fondaparinux and 1.1 percent of those treated with unfractionated heparin. Mortality rates at three months were similar in the two groups. Of the patients in the fondaparinux group, 14.5 percent received the drug in part on an outpatient basis.. Once-daily, subcutaneous administration of fondaparinux without monitoring is at least as effective and is as safe as adjusted-dose, intravenous administration of unfractionated heparin in the initial treatment of hemodynamically stable patients with pulmonary embolism.

Topics: Aged; Drug Administration Schedule; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Humans; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Polysaccharides; Pulmonary Embolism; Secondary Prevention; Single-Blind Method

Surgery for hip fracture carries a high risk of venous thromboembolism, despite the use of current thromboprophylactic treatments. Fondaparinux, a synthetic pentasaccharide, is a new antithrombotic agent that may reduce this risk.. In a double-blind study, were randomly assigned 1711 consecutive patients undergoing surgery for fracture of the upper third of the femur to receive subcutaneous doses of either 2.5 mg of fondaparinux once daily, initiated postoperatively, or 40 mg of enoxaparin once daily, initiated preoperatively, for at least five days. The primary efficacy outcome was venous thromboembolism up to postoperative day 11. Venous thromboembolism was defined as deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or documented symptomatic pulmonary embolism. The main safety outcomes were major bleeding and mortality from all causes. The duration of follow-up was six weeks.. The incidence of venous thromboembolism by day 11 was 8.3 percent (52 of 626 patients) in the fondaparinux group and 19.1 percent (119 of 624 patients) in the enoxaparin group (P<0.001). The reduction in risk with fondaparinux was 56.4 percent (95 percent confidence interval, 39.0 to 70.3 percent). There were no significant differences between the two groups in the incidence of death or clinically relevant bleeding.. In patients undergoing surgery for hip fracture, fondaparinux was more effective than enoxaparin in preventing venous thromboembolism and equally safe.

Topics: Aged; Double-Blind Method; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Hip Fractures; Humans; Incidence; Injections, Subcutaneous; Male; Mortality; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Thromboembolism; Venous Thrombosis

Despite thromboprophylaxis, major knee surgery carries a high risk of venous thromboembolism. Fondaparinux, the first of a new class of synthetic antithrombotic agents, may reduce this risk.. In a double-blind study, we randomly assigned 1049 consecutive patients undergoing elective major knee surgery to receive subcutaneous doses of either 2.5 mg of fondaparinux once daily or 30 mg of enoxaparin twice daily, with both treatments initiated postoperatively. The primary efficacy outcome was venous thromboembolism up to postoperative day 11, defined as deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or documented symptomatic pulmonary embolism. The primary safety outcome was major bleeding.. The primary efficacy outcome was assessed in 724 patients. The fondaparinux group had a significantly lower incidence of venous thromboembolism by day 11 (12.5 percent [45 of 361 patients]) than the enoxaparin group (27.8 percent [101 of 363 patients]; reduction in risk, 55.2 percent; 95 percent confidence interval, 36.2 to 70.2; P<0.001). Major bleeding (including overt bleeding with a bleeding index of 2 or more) occurred more frequently in the fondaparinux group (P=0.006), but there were no significant differences between the two groups in the incidence of bleeding leading to death or reoperation or occurring in a critical organ.. In patients undergoing elective major knee surgery, postoperative treatment with 2.5 mg of fondaparinux once daily was significantly more effective in preventing deep-vein thrombosis than 30 mg of enoxaparin twice daily.

Topics: Aged; Double-Blind Method; Drug Administration Schedule; Elective Surgical Procedures; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Incidence; Injections, Subcutaneous; Knee; Male; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Thromboembolism; Venous Thrombosis

Objective Venous thromboembolism (VTE) is a common cancer complication. Patients with cancer have a high risk of recurrent VTE and bleeding. We analyzed the effectiveness of VTE treatment via subcutaneous fondaparinux injection for patients with and without cancer. Methods This study included 260 inpatients who had received fondaparinux therapy. Fondaparinux's therapeutic effect was quantitatively and qualitatively evaluated by imaging tests. To quantitatively evaluate the deep vein thrombosis (DVT) clot burden of the lower limbs, we calculated the quantitative ultrasound thrombosis (QUT) score, which was devised by our institution. Results There were 80 and 180 patients with and without cancer, respectively. The QUT score significantly reduced after treatment in both groups (cancer: 6.70±4.37 vs. 4.19±4.17, p<0.001; noncancer: 7.08±4.37 vs. 4.17±3.94, p<0.001). The changes in the QUT score showed no significant difference between the 2 groups (cancer: 2.23±3.09; noncancer: 3.04±3.45, p=0.06). In addition, the quantitative evaluation of pulmonary thromboembolism (PTE) after treatment showed that PTE decreased or disappeared in 38/40 patients (95.0%) in the cancer group and 55/63 patients (87.3%) in the noncancer group, indicating no significant difference in the improvement rate between the groups. Conclusion Fondaparinux was effective for VTE both in patients with and without cancer, with no significant differences in the changes in the QUT score. However, the change in the QUT score was smaller in patients with cancer than in those without cancer, suggesting that the efficacy of fondaparinux might be diminished in patients with cancer.

Topics: Anticoagulants; East Asian People; Fondaparinux; Humans; Neoplasms; Polysaccharides; Pulmonary Embolism; Venous Thromboembolism; Venous Thrombosis

Long term incidence of symptomatic venous thromboembolism (VTE) and bleeding events in patients with superficial vein thrombosis (SVT) was investigated.. In this prospective, observational study, patients with acute SVT were treated at the discretion of the responsible physician. The primary efficacy outcome was symptomatic VTE including deep vein thrombosis (DVT), pulmonary embolism (PE), and recurrent or extending SVT. The primary safety outcome was clinically relevant bleeding, recorded at periodic clinic visits over a 12 month period.. The mean age of 872 patients with 12 month follow up was 60.6 ± 14.5 years, 64.5% were female, 80.1% had chronic venous disease (defined as chronic venous insufficiency and or varicose veins), and 41.9% had a history of VTE. They were receiving fondaparinux in 62.1% (mean duration 34.9 ± 15.7 days), low molecular weight heparin (LMWH) in 25.0% (mean duration 26.2 ± 23.2 days), any other anticoagulants in 6.2%, and no anticoagulant in 6.7%. At 12 months, 108 patients (14.3%) achieved the primary efficacy outcome. The most common VTE event was recurrent or extending SVT in 11.0%, followed by symptomatic DVT in 2.7%, symptomatic PE in 2.4%, hospitalisation due to VTE in 1.8%, and death in 1.1%. Clinically relevant bleeding events occurred in 2.1% of patients, and major bleedings in 0.3%. By drug, the rate of the primary efficacy outcome was highest in the LMWH group (22.4%) and lowest in the fondaparinux group (10.4%). In a multivariable model, patients with events between three months and 12 months were significantly more likely to have higher BMI (hazard ratio [HR] 1.06; p = .002), history of VTE (HR 2.89; p = .002), and severe systemic infections (HR 7.59; p = .006).. The risk of symptomatic VTE remained elevated over 12 months of follow up. Therefore, anticoagulation beyond 45 days may be considered in patients with risk factors. [ClinicalTrials.gov identifier: NCT02699151.].

Topics: Aged; Anticoagulants; Female; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Varicose Veins; Venous Thromboembolism; Venous Thrombosis

COVID-19 became a widespread infectious disease in late 2019. Indonesia currently has the highest COVID-19 mortality rate in Asia, between 4-5 percent. Interestingly, COVID-19-associated coagulopathy characterized by an increase of several procoagulant factor levels, including fibrinogen and D-dimer, that has been associated with higher mortality and unfavorable outcomes. We report a case of a 30-year-old male admitted to the hospital with a profuse vomiting and worsening fever, cough and shortness of breath, and was diagnosed with COVID-19-associated coagulopathy. Seven days after admission, he became deteriorated with significant reduction of oxygen saturation and his coagulation parameter levels were increased with highly suspicion of pulmonary embolism. He was treated with azithromycin, isoprinosine, lopinavir, and fondaparinux with thromboprophylaxis dosage since admission. The role of increased fondaparinux dosage at the time of clinical deterioration was then followed by clinical improvement and reduced D-dimer level. Anticoagulant therapy, mainly with fondaparinux, showed a better prognosis in patients with markedly elevated D-Dimer. Fondaparinux needs to be monitored appropriately to prevent bleeding and adverse. The patient was discharged from the hospital in an improved condition and normal D-Dimer levels. There was no bleeding event nor other major side effects had been found in this case. The decision for increasing dose of anticoagulant may be determined on individual basis, considering risks, benefits, and also the most important is clinical findings.

Topics: Adult; Antiviral Agents; Azithromycin; Clinical Deterioration; COVID-19; COVID-19 Drug Treatment; Dose-Response Relationship, Drug; Drug Monitoring; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Fondaparinux; Hemorrhage; Humans; Inosine Pranobex; Lopinavir; Male; Pulmonary Embolism; SARS-CoV-2; Thrombophilia; Treatment Outcome

A definitive diagnosis of heparin-induced thrombocytopenia (HIT) is difficult to make, especially in patients undergoing cardiac surgery. In this retrospective cohort study, we assessed the platelet count trends and the response to fondaparinux in a population of patients of suspected HIT after pulmonary endarterectomy (PEA). Patients enrolled in this study were over the age of 18 years, and survived longer than 7 days after PEA between January 1, 2011 and December 31, 2015. HIT likelihood was assessed by the 4 T's score and interpreted by our institutional algorithm. 54 patients were operated, and 49 patients met the inclusion criteria. Six patients met the criteria for suspected HIT and were treated with fondaparinux until the platelet recovered. No significant difference was observed of clinical characteristics between intermediate to high HIT likelihood patients (HIT SUSPECTED) and low HIT likelihood patients (NO HIT SUSPECTED). HIT SUSPECTED patients reached platelet count lowest later (about 5.5 days after PEA), while NO HIT SUSPECTED patients is about 4.0 days after PEA. Percentage of platelet counts decrease (> 50%) was larger than NO HIT SUSPECTED patients (< 50%). There was no difference in mortality or residual pulmonary hypertension between HIT SUSPECTED and NO HIT SUSPECTED patients. Two HIT SUSPECTED patients who used heparin after PEA died, the other four survived by replacing heparin or low molecular weight heparin with fondaparinux. Suspected HIT patients should be surveilled carefully. Platelet counts trends may have some hints in the prevention of HIT. Fondaparinux may be effective for patients with suspected HIT.

Topics: Adult; China; Cohort Studies; Endarterectomy; Factor Xa Inhibitors; Female; Fondaparinux; Heparin; Humans; Hypertension, Pulmonary; Male; Middle Aged; Platelet Count; Postoperative Complications; Pulmonary Embolism; Risk Adjustment; Thrombocytopenia

Management and outcomes of superficial vein thrombosis (SVT) are highly variable and not well described. Therefore, the INvestigating SIGnificant Health TrendS in the management of SVT (INSIGHTS-SVT) study collected prospective data under real life conditions.. Prospective observational study of objectively confirmed acute isolated SVT. The primary outcome was a composite of symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), and extension or recurrence of SVT at three months. The primary safety outcome was clinically relevant bleeding.. A total of 1 150 patients were included (mean age 60.2 ± 14.7 years; 64.9% women; mean BMI 29.4 ± 6.3 kg/m. At three month follow up, patients with isolated SVT are at risk of thromboembolic complications (mainly recurrent or extended SVT), despite anticoagulation. In this real life study, about one third had received either heparins, oral anticoagulants, or no anticoagulation.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Leg Ulcer; Lower Extremity; Male; Middle Aged; Prospective Studies; Pulmonary Embolism; Recurrence; Risk Factors; Stockings, Compression; Treatment Outcome; Varicose Veins; Venous Insufficiency; Venous Thrombosis

This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously.. We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology.. The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update.. New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.

Topics: Drug Therapy, Combination; Evidence-Based Medicine; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Injections, Intravenous; Injections, Subcutaneous; International Normalized Ratio; Pulmonary Embolism; Risk Assessment; Thrombolytic Therapy; Venous Thrombosis; Vitamin K

We aimed to investigate the clinical performance of edoxaban for the treatment of pulmonary embolism (PE) in hospitalized COVID-19 patients.. We conducted a retrospective analysis selecting hospitalized patients with COVID-19 admitted to our Institution from 20 May 2020 to 20 November 2020 with computer tomography (CT) detected PE at admission, treated with edoxaban after initial parenteral therapy. Clinical outcomes were compared between patients with and without ARDS at admission and between those with and without CT confirmed PE resolution.. 50 patients were included. Mean follow-up was 42.5 ± 10 days. No baseline differences were found between patients with ARDS (30%) and those without ARDS at admission. Patients with PE resolution (84%) were younger (. Edoxaban was an effective and safe treatment for acute PE in COVID-19 setting.

Topics: Adult; Aged; COVID-19; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Pulmonary Embolism; Pyridines; Respiratory Distress Syndrome; Retrospective Studies; SARS-CoV-2; Thiazoles

The safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) for the treatment of venous thromboembolism (VTE) have been established in randomized controlled trials, but limited data are available on their use in clinical practice across geographical regions.. In the international RE-COVERY DVT/PE observational study (enrollment January 2016 to May 2017), we sought to characterize the patient population and describe the prescribed anticoagulant. Patient characteristics and anticoagulants administered after objective diagnosis of VTE were recorded at the baseline visit and again at hospital discharge or at 14 days after the diagnosis, whichever was later.. A total of 6095 patients were included, 50.2% were male, and the mean age was 61.5 years. The most common comorbidities were hypertension (35%), diabetes mellitus (11%), cancer (11%), prior VTE(11%), and trauma/surgery (7%). Overall, 77% of patients received oral anticoagulants, with 54% on NOACs and 23% on vitamin K antagonists (VKAs); 20% received parenteral anticoagulation only. NOACs comprised about 60% of anticoagulant treatment in Europe and Asia but substantially less in Latin America (29%) and the Middle East (21%). For NOAC therapies, the distribution (as a percentage of the total cohort) was rivaroxaban 25.6%, dabigatran 15.5%, apixaban 11.3%, and edoxaban 1.7%. Treatment with NOACs was less frequent in patients who had cancer, chronic renal disease, heart failure, or stroke.. These findings enhance our understanding of baseline characteristics and the initial management of patients with VTE in routine practice.

Topics: Administration, Oral; Adult; Age Distribution; Aged; Anticoagulants; Asia; Comorbidity; Cross-Sectional Studies; Dabigatran; Diabetes Mellitus; Europe; Factor Xa Inhibitors; Female; Fondaparinux; Heparin; Humans; Hypertension; Latin America; Male; Middle Aged; Middle East; Neoplasms; Postoperative Complications; Practice Patterns, Physicians'; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Wounds and Injuries

Hepatotoxicity with low-molecular-weight heparin (LMWH) or fondaparinux is a relatively common adverse reaction. This study assessed the effects of LMWH and fondaparinux on liver function in patients with pulmonary embolism based on a retrospective cohort. As a result, a total of 463 patients with pulmonary embolism and treated with LMWH (enoxaparin sodium or nadroparin calcium) or fondaparinux sodium were included. Liver dysfunction was identified in 79 patients (17.1%), of whom 97.5% had grade 1 drug-induced liver injury (DILI) and 2.5% had grade 2 DILI. The results showed that liver dysfunction usually occurred in the first week after anticoagulant administration, and the liver tests of all patients with liver dysfunction gradually recovered or alleviated at discharge. The multivariable logistic regression analysis indicated that a longer treatment course and hepatitis B surface antigen-positive (HBsAg+) were risk factors for liver dysfunction (P < .05). Moreover, nadroparin calcium had the highest risk of liver dysfunction, approximately 2.2 times (95% confidence interval [CI], 1.1740-4.224; P = .015) that of enoxaparin sodium. In conclusion, nearly one-fifth and 10% of patients prescribed with LMWH or fondaparinux, respectively, for pulmonary embolism had liver dysfunction, mainly with mild liver injury and characterized by self-limited elevated serum transaminase levels. Hence, during the 3 anticoagulant applications, we should pay more attention to the monitoring of liver function in the first week and transit to oral anticoagulants if possible, especially for patients who are HBsAg+ or suffering from other liver diseases.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Asian People; Chemical and Drug Induced Liver Injury; Drug Combinations; Enoxaparin; Factor Xa Inhibitors; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Hepatitis B Surface Antigens; Humans; Liver; Male; Middle Aged; Nadroparin; Pulmonary Embolism; Retrospective Studies; Risk Factors; Time Factors

The present article addresses clinical challenges associated with the choice of the anticoagulant agent, the definition of the duration of anticoagulant treatment and the assessment of the risk-to-benefit ratio of prolonged anticoagulation for patients with pulmonary embolism (PE).Anticoagulation is performed with unfractionated heparin (UFH) in hemodynamically unstable patients and with low molecular weight heparins (LWMH) or fondaparinux in normotensive patients. In patients with high or intermediate clinical probability of pulmonary embolism, anticoagulation should be initiated without delay while awaiting the results of diagnostic tests. LMWH and fondaparinux are preferred over UFH in the initial anticoagulation of PE since they are associated with a lower risk of bleeding.All patients with PE require therapeutic anticoagulation for at least three months. The current 2019 guidelines of the European Society of Cardiology (ESC) recommend that all eligible patients should be treated with a non-vitamin K antagonist oral anticoagulant (NOAC) in preference to a vitamin K antagonist (VKA). In patients with active cancer, Apixaban, Edoxaban and Rivaroxaban are effective alternatives to treatment with LMWH.The decision on the duration of anticoagulation should consider both, the individual risk of PE recurrence and the individual risk of bleeding. The risk for recurrent PE after discontinuation of treatment is related to the features of the index PE event. While patients with a strong transient risk factor have a low risk of recurrence and anticoagulation can be discontinued after three months, patients with strong persistent risk factor (such as active cancer) have a high risk of recurrence and thus should receive anticoagulant treatment of indefinite duration. Given the favourable safety profile of NOACs (especially if a reduced dosage of Apixaban or Rivaroxaban is initiated after at least six months of therapeutic anticoagulation), extended oral anticoagulation of indefinite duration should be considered for all patients with intermediate risk of recurrence.

Topics: Acute Disease; Dalteparin; Dose-Response Relationship, Drug; Drug Administration Schedule; Fibrinolytic Agents; Fondaparinux; Guideline Adherence; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Long-Term Care; Neoplasms; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Recurrence; Risk Assessment; Risk Factors; Rivaroxaban; Thiazoles

The use of heparin has been shown to decrease the mortality in hospitalized patients with severe COVID-19. The aim of our study was to evaluate the clinical impact of venous thromboembolism prophylaxis with fondaparinux versus enoxaparin among 100 hospitalized COVID-19 patients. The incidence of pulmonary embolism, deep venous thrombosis, major bleeding (MB), clinically relevant non-MB, acute respiratory distress syndrome, and in-hospital mortality was compared between patients on fondaparinux versus enoxaparin therapy. The 2 groups were homogeneous for demographic, laboratory, and clinical characteristics. In a median follow-up of 28 (IQR: 12-45) days, no statistically significant difference in venous thromboembolism (14.5% vs. 5.3%; P = 0.20), MB and clinically relevant non-MB (3.2% vs. 5.3%, P = 0.76), ARDS (17.7% vs. 15.8%; P = 0.83), and in-hospital mortality (9.7% vs. 10.5%; P = 0.97) has been shown between the enoxaparin group versus the fondaparinux group. Our preliminary results support the hypothesis of a safe and effective use of fondaparinux among patients with COVID-19 hospitalized in internal medicine units.

Topics: Aged; Anticoagulants; Antithrombins; Coronavirus Infections; COVID-19; Enoxaparin; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Hospital Mortality; Humans; Incidence; Male; Middle Aged; Pandemics; Pneumonia, Viral; Pulmonary Embolism; Retrospective Studies; Venous Thromboembolism; Venous Thrombosis

Deep vein thrombosis and pulmonary artery embolisms share pathophysiological features and are therefore collectively referred to as venous thromboembolisms (VTE). While the incidence of VTE has been increasing for years as a result of demographic changes and improved diagnostics, the morbidity and mortality are decreasing. This is particularly due to more sensitive diagnostics, improvements in risk stratification and more effective anticoagulation strategies. The aim of effective anticoagulation therapy is the avoidance of early events up to death and prevention of recurrent events. Anticoagulation treatment should be started with either heparins (unfractionated or low molecular weight), the pentasaccharide fondaparinux or direct oral anticoagulants. Patients with recurrent events qualify for indefinite anticoagulation treatment. For a first episode of VTE anticoagulation treatment for at least 3 months is recommended (maintenance therapy). Subsequently, prolonged maintenance therapy for secondary prevention can be meaningful, depending on the individual patient risk (provoked event, risk for recurrence or bleeding). The non-vitamin K antagonist oral anticoagulants (NOACs) have now also been approved for this indication. As a result of a probably permanently high risk for recurrent events of up to 10% per year after cessation of anticoagulation, insufficient scores for estimation of the risk of bleeding and recent data documenting the safety and efficacy of NOACs for secondary prevention, a shift towards prolonged anticoagulation of 3-6 months or even indefinite (>1 year) treatment can be anticipated for patients after thromboembolic diseases.

Topics: Administration, Oral; Algorithms; Anticoagulants; Drug Administration Schedule; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Long-Term Care; Pulmonary Embolism; Recurrence; Risk Factors; Secondary Prevention; Survival Rate; Venous Thrombosis

There are numerous studies discussing thromboprophylaxis after total joint arthroplasty (TJA), with varying conclusions. Patient inclusion criteria may be different for each study, which may lead to selection bias and misrepresentation of data. This study aimed to investigate if industry funding impacted patient demographics and overall reported outcomes of studies analyzing venous thromboembolism (VTE) prevention after TJA.. Electronic searches were completed using Ovid, PubMed, and Embase databases. Studies were included if (1) they are published in the English language between 2000 and 2016; (2) they included patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA); and (3) they evaluated prevention and control of postoperative VTE with at least one of the following thromboprophylactic agents: aspirin, enoxaparin, dalteparin, dabigatran, apixaban, rivaroxaban, dabigatran, ximelagatran, fondaparinux, or coumadin. Data were extracted and analyzed via mixed-effect logistic regression.. Fifty-seven studies were included; 29 were industry funded, and 28, nonfunded. There were no significant differences between patient's age, body mass index, or revision exclusions between funded and nonfunded studies. Funded studies reported less pulmonary embolisms, fewer events of major bleeding, and significantly less 90-day mortality compared with nonfunded studies.. Industry-funded studies reported less pulmonary embolisms, major bleeding, and mortality compared with nonfunded studies. Detailed demographic data were missing from the literature, and we were unable to demonstrate the cause of different reported outcomes between industry-funded and nonfunded studies. Further investigations should be aimed toward understanding how funded studies report less adverse outcomes in analyzing VTE after TJA.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Conflict of Interest; Dabigatran; Enoxaparin; Female; Fondaparinux; Health Care Sector; Hemorrhage; Humans; Male; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Venous Thromboembolism; Warfarin

Rates of venous thromboembolism in contemporary studies of primary total knee arthroplasty (TKA) have been reported to be as high as 3.5%. Although drug prophylaxis is effective, the best option among these regimens is not well established. The purpose of this study was to evaluate the comparative effectiveness and safety of aspirin, low-molecular-weight heparin, synthetic pentasaccharide factor Xa inhibitors, and vitamin K antagonist.. Data were from a US total joint replacement registry, with 30,499 patients receiving unilateral TKA from May 16, 2006, to December 31, 2013. Patients received either aspirin (324-325 mg daily), enoxaparin (40-60 mg daily), fondaparinux (2.5 mg daily), or warfarin (all doses) and were followed up 90 days postoperatively on several outcomes: deep vein thrombosis, pulmonary embolism, major bleeding, wound complications, infection, and death.. There was no evidence that fondaparinux, enoxaparin, or warfarin were superior to aspirin in the prevention of pulmonary embolism, deep vein thrombosis, or venous thromboembolism or that aspirin was safer than these alternatives. However, enoxaparin was found to be as safe as aspirin with respect to bleeding, and fondaparinux was as safe as aspirin for risk of wound complications.. Among TKA patients, we did not find evidence for decreased effectiveness or increased safety with use of aspirin, but enoxaparin had comparable safety to aspirin for bleeding and fondaparinux had comparable safety to aspirin for wound complications.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Aspirin; Cohort Studies; Enoxaparin; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Polysaccharides; Pulmonary Embolism; Venous Thromboembolism; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) frequently occurs in patients undergoing total knee arthroplasty (TKA). This study aimed to evaluate the efficacy of dielectric blood coagulometry (DBCM) as a new technique for predicting postoperative VTE.. Thirty patients undergoing TKA were enrolled. DVT was diagnosed by ultrasonography preoperatively and on the fourth or fifth postoperative day. Enhanced computed tomography was performed to detect PE on the fourth postoperative day. The day after surgery, a blood sample was measured by DBCM. All patients received fondaparinux or low-molecular-weight heparin for postoperative thromboprophylaxis.. Eighteen of the 30 patients had DVT postoperatively, and 10 had asymptomatic PE. Seven patients had both DVT and PE. The patterns of permittivity as a function of time and frequency from the DBCM measurement were different between patients with and without VTE. The sensitivity and specificity of the parameter constructed from a set of permittivities at the frequencies of 2.5 kHz, 1 MHz, and 10 MHz were 90% and 78%, respectively.. DBCM was effective and efficient for predicting VTE after TKA.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Blood Coagulation; Blood Coagulation Tests; Computed Tomography Angiography; Dielectric Spectroscopy; Feasibility Studies; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Polysaccharides; Predictive Value of Tests; Pulmonary Embolism; Risk Factors; Time Factors; Treatment Outcome; Ultrasonography; Venous Thromboembolism; Venous Thrombosis

The factor Xa inhibitors have been widely used for the treatment and prevention of venous thromboembolism (VTE). However, the efficacy of factor Xa inhibitors in Japanese patients with VTE has not been well examined. In this study, we investigated the effect of the sequential use of two factor Xa inhibitors in patients with acute VTE.. We conducted an observational study of 87 consecutive patients diagnosed with VTE. As an initial treatment, we administered subcutaneous fondaparinux to the patients for 7-10 days, and then switched to oral rivaroxaban. The symptoms and findings were assessed after the initial treatment and after using rivaroxaban for 7-14 days. We evaluated the deep vein thrombosis (DVT) in the legs using our own scoring system [quantitative ultrasound thrombosis (QUT) score].. Of the 87 patients, 33% had symptoms, half had pulmonary embolism (PE), and 95% had DVT of the legs. Out of the 87 patients, VTE worsened during the administration of fondaparinux in 4 patients. All of them had experienced malignancy, and died within 6 months. Of two patients developing bleeding, one patient required a transfusion. Eventually, this strategy was effective in 80 patients and had no change in one. The D-dimer level was significantly reduced by fondaparinux (17.8μg/ml±16.0μg/ml vs. 8.3μg/ml±7.2μg/ml, p<0.0001), followed by rivaroxaban (8.3μg/ml±7.2μg/ml vs. 5.5μg/ml±4.9μg/ml, p<0.0001). Similarly, the QUT score was improved by fondaparinux (4.7±2.6 vs. 2.5±2.5, p<0.0001), and further reduced by rivaroxaban (2.5±2.5 vs. 1.9±1.8, p<0.0001).. A treatment strategy using subcutaneous fondaparinux followed by oral rivaroxaban is effective for treating acute VTE in Japanese patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Polysaccharides; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

For a long time, superficial venous thrombosis (SVT) of the lower limbs was considered as benign. Due to lack of clear scientific evidence, its treatment was heterogeneous and even potentially deleterious. Since 2010, several major studies have highlighted the seriousness of SVT, and prophylactic doses of fondaparinux have proven their efficacy for this indication. While the French recommendations have not yet taken on board all this data, has practice already changed?. To describe in general practice the usual management of suspected SVT.. A descriptive cross-sectional study of general practitioners in Saône-et-Loire. Each doctor taking part was asked to note on a paper questionnaire the details of the last patient in whom they suspected SVT. Data collected included: clinical presentation, diagnostic and therapeutic management and follow-up of the patients.. Between 01/01/2014 and 31/03/2014, 88 doctors out of 443 contacted (20%) completed the questionnaire. According to the information they provided, 36 physicians (40.9% [95% CI: 30.6-50.2]) searched for an associated pulmonary embolism. Eighty-two physicians (93.2% [95% CI: 87.9-98.4]) prescribed a venous compression ultrasound (CUS) exploration. Twelve etiological assessments were carried out (13.6% [95% CI: 6.5-20.8]) of which 6 (6.8%) appeared to be justified. 64 (72.7%) of the patients were given an anticoagulant therapy (heparin or fondaparinux), including 15 (17%) at a prophylactic dose and 49 (55.7%) at a curative dose. Forty-nine doctors (55.7% [95% CI: 45.3-66.1]) prescribed a CUS follow-up.. General practitioners seem to have adapted their diagnostic practices to the data highlighting the potential seriousness of SVT. The treatment they give, however, remains very variable and potentially deleterious, in particular due to a high rate of treatments given at curative doses.

Topics: Anti-Inflammatory Agents; Anticoagulants; Cross-Sectional Studies; Fibrin Fibrinogen Degradation Products; Fondaparinux; France; General Practitioners; Health Care Surveys; Heparin; Humans; Leg; Platelet Aggregation Inhibitors; Polysaccharides; Practice Patterns, Physicians'; Pulmonary Embolism; Risk Factors; Stockings, Compression; Surveys and Questionnaires; Ultrasonography, Doppler; Venous Thrombosis

The efficacy and safety of the anticoagulant rivaroxaban for the treatment and secondary prevention of deep-vein thrombosis and pulmonary embolism has been shown in phase 3 trials. However, data about rivaroxaban use in routine clinical practice are needed.. XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was a multicentre, international, prospective, non-interventional study of patients with deep-vein thrombosis, done in hospitals and community care centres in 21 countries. The study investigated the safety and effectiveness of rivaroxaban compared with standard anticoagulation therapy (initial treatment with unfractionated heparin, low-molecular-weight heparin, or fondaparinux, usually overlapping with and followed by a vitamin K antagonist) for at least 3 months. Eligible patients were adults (aged ≥18 years) with an objectively confirmed diagnosis of deep-vein thrombosis, and an indication to receive anticoagulation treatment for at least 3 months. Following approval of rivaroxaban for the pulmonary embolism indication, patients with deep-vein thrombosis and concomitant pulmonary embolism were also eligible; however, those with isolated pulmonary embolism were not included. Type, dose, and duration of therapy for each patient were at the physician's discretion. The primary effectiveness and safety outcomes were major bleeding, recurrent venous thromboembolism, and all-cause mortality. Propensity score-adjusted analyses were done to account for potential imbalances between groups. This study is registered with ClinicalTrials.gov, number NCT01619007.. Between June 26, 2012, and March 31, 2014, 5142 patients were enrolled. The safety population (all patients who received at least one dose of the anticoagulant of interest) comprised 2619 patients in the rivaroxaban group and 2149 in the standard anticoagulant therapy group. Patients in the rivaroxaban group were younger and fewer had active cancer or concomitant pulmonary embolism than those in the standard anticoagulation group. In the propensity score-adjusted population, the frequency of major bleeding was 0·8% (19/2505) in the rivaroxaban group and 2·1% (43/2010) in the standard anticoagulation group, with a propensity score-adjusted hazard ratio (HR) of 0·77 (95% CI 0·40-1·50); p=0·44. The frequency of recurrent venous thromboembolism was 1·4% (36/2505) in the rivaroxaban group and 2·3% (47/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·91 [95% CI 0·54-1·54], p=0·72). The all-cause mortality frequency was 0·4% (11/2505) in the rivaroxaban group and 3·4% (69/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·51 [95% CI 0·24-1·07], p=0·074). The incidence of treatment-emergent adverse events in the safety population was similar between the two groups (944 [36·0%] of 2619 in the rivaroxaban group vs 805 [37·5%] of 2149 in the standard anticoagulation group).. In routine clinical practice, rivaroxaban-treated patients had a lower risk profile at baseline than those treated with standard anticoagulation. Propensity score-adjusted results confirm that rivaroxaban is a safe and effective alternative to standard anticoagulation therapy in a broad range of patients. Rates of major bleeding and recurrent venous thromboembolism were low in rivaroxaban-treated patients and consistent with phase 3 findings.. Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.

Topics: Aged; Anticoagulants; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Middle Aged; Polysaccharides; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

The aim of this study was to estimate the effect of fondaparinux and enoxaparin combined with mechanical prophylaxis (MP) after total hip arthroplasty (THA) and total knee arthroplasty (TKA). We also investigated the occurrence of pulmonary embolism (PE) and its associated risk factors.. Data were retrospectively collected on patients who underwent THA or TKA between 2008 and 2010 from the Japanese Diagnosis Procedure Combination database (n = 49,678). We extracted information on sex, age, main diagnosis, types of anesthesia, duration of anesthesia, comorbidities, hospital volume, the use of MP, and the use of anticoagulant drugs.. The overall occurrence of PE was 0.41%. Multivariate logistic regression analysis showed that the occurrence of PE was significantly higher in females (odds ratio, 2.17; p < 0.001, compared with males), TKA (1.47; p = 0.039, compared with THA), and longer-duration anesthesia (2.63; p = 0.008 in the ≥ 240-min. group compared with the ≤ 119-min. group). Compared with the MP-alone group, the occurrence of PE was significantly reduced in the fondaparinux group (0.58; p = 0.025) and the enoxaparin group (0.59; p = 0.046).. Fondaparinux or enoxaparin combined with MP decreased the occurrence of PE. The risk factors for PE were female patients, TKA, and longer-duration anesthesia (≥ 240 min.).

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Databases, Factual; Diagnostic Imaging; Enoxaparin; Factor X; Female; Fondaparinux; Humans; Japan; Male; Middle Aged; Odds Ratio; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Retrospective Studies; Risk Factors

There is scarce evidence to identify which acutely ill medical patients might benefit from prophylaxis against venous thromboembolism (VTE).. The Spanish National Discharge Database was used to identify predictors of bleeding and VTE during hospitalization for an acute medical illness.. Of 1,148,301 patients, 3.10% bled, 1.21% were diagnosed with VTE, and 8.64% died. The case-fatality rate was: 20.8% for bleeding and 19.7% for VTE. Eight clinical variables were independently associated with an increased risk for VTE and bleeding, one with a decreased risk for both events, 4 with an increased risk for VTE and a decreased risk for bleeding, 2 with an increased risk for bleeding but a decreased risk for VTE, and 1 with a decreased risk for bleeding. When all these variables were considered, we composed a risk scoring system, in which we assigned points to each variable according to the ratio between the odds ratio for bleeding and for VTE. Overall, 21% of patients scored less than 0 points and had a bleeding vs. VTE ratio of 1.19; 55% scored 0 to 1.0 points and had a ratio of 2.13; and 24% scored over 1.0 points and had a ratio of 6.10.. A risk score based on variables documented at admission can identify patients with different ratios (near 1.0; about 2.0; and >6.0) between the rate of bleeding and of VTE.

Topics: Acute Disease; Aged; Aged, 80 and over; Anticoagulants; Chemoprevention; Comorbidity; Databases, Factual; Female; Fondaparinux; Heart Failure; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Male; Middle Aged; Polysaccharides; Pulmonary Embolism; Respiratory Insufficiency; Risk Assessment; Risk Factors; Spain; Venous Thromboembolism; Venous Thrombosis

Pulmonary embolism (PE) is recognized as an important complication in patients undergoing hip fracture surgery. However, clinical evidence demonstrating the effectiveness of pharmacological thromboprophylaxis, including fondaparinux, is limited because the occurrence of postoperative PE after hemiarthroplasty is very low. The goal of this study was to analyze the effect of fondaparinux in reducing PE following hemiarthroplasty for femoral neck fracture using large-scale retrospective data.. Employing data from the Japanese Diagnosis Procedure Combination database from July 1 to December 31 between 2007 and 2010, we retrospectively identified 22,776 patients who underwent hemiarthroplasty for femoral neck fracture; we included those who received mechanical prophylaxis alone (n = 17,984) and those who received both mechanical prophylaxis and pharmacological prophylaxis with fondaparinux (n = 4,792). Logistic regression analysis was performed to compare the occurrence of postoperative PE with adjustment for sex, age, comorbidities, and type and duration of anesthesia.. The mean age of the patients was 79.5 ± 9.4 years. Overall, postoperative PE occurred in 189 (0.83%) patients. The rate of postoperative PE in the fondaparinux group (0.61%) was lower than in the control group (0.89%), although the difference was not significant in the univariate analysis (odds ratio [OR] 0.68; p = 0.055). In the multivariate analysis, the fondaparinux group showed a significantly lower rate of postoperative PE than the group receiving mechanical prophylaxis alone (OR 0.67; p = 0.047). General anesthesia and a longer duration of anesthesia were significant risk factors for postoperative PE.. Fondaparinux combined with mechanical prophylaxis is more effective in preventing postoperative PE following hemiarthroplasty for femoral neck fracture than mechanical prophylaxis alone.

Topics: Aged; Aged, 80 and over; Anticoagulants; Databases, Factual; Dose-Response Relationship, Drug; Factor X; Female; Femoral Neck Fractures; Fondaparinux; Hemiarthroplasty; Humans; Incidence; Japan; Male; Odds Ratio; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Retrospective Studies; Risk Factors

To assess adherence to French guidelines for curative treatment of thromboembolism in cancer patients, and to identify factors limiting their implementation.. Retrospective analysis of the medical files of cancer patients diagnosed with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in one site between January 1st, 2010 and June 30th, 2011. Central venous catheter thrombosis and superficial vein thrombosis were excluded.. The series included 145 patients, among whom 113 (78%) had solid tumors (at a metastatic stage in 68% of cases) and 33 (22%) had hematologic malignancies. Low molecular weight heparin (LMWH) was prescribed as long-term treatment (>10 days) for 83 patients (57.2%) and a vitamin K antagonist (VKA) for 33 patients (22.7%). Bleeding required treatment modifications or discontinuation in 11 (7.5%) and 10 (6.8%) patients respectively. After 6 months, LMWH, VKA and fondaparinux were prescribed for 28, 27 and six (19.3%, 18.6% et 4.1%) patients respectively. Mean duration of anticoagulation was 176.8 days. Treatment was not affected by a history of venous thromboembolism, the presence of pulmonary embolism or proximal deep vein thrombosis but it was significantly shorter in case of thrombosis limited to muscular veins (115.5 vs 182.3 days, P<0.05). Overall, guidelines were fully implemented in only 68 (46.9%) patients, with regards to the choice of pharmacological class and duration of treatment.. Adherence to national guidelines is insufficient and actions must be taken to improve the management of venous thromboembolism in cancer patients.

Topics: 4-Hydroxycoumarins; Adult; Aged; Aged, 80 and over; Anticoagulants; Drug Administration Schedule; Drug Utilization; Female; Fondaparinux; France; Guideline Adherence; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasms; Polysaccharides; Practice Patterns, Physicians'; Pulmonary Embolism; Retrospective Studies; Thrombophilia; Thrombophlebitis; Ultrasonography, Doppler; Venous Thrombosis

Heparin-induced thrombocytopenia is a potentiallylife-threatening complication of heparin or low-molecular-weight heparin administration. We describe the case of a patient with heparin-induced thrombocytopenia complicated by pulmonary embolism, successfully treated with fondaparinux, a factor Xa inhibitor. We also review the literature regarding the use of this anticoagulant in heparin-induced thrombocytopenia complicated by thrombosis. Few treatment options are available in Belgium, and there is little evidence regarding newer anticoagulants.

Topics: Aged, 80 and over; Anticoagulants; Factor X; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Pulmonary Embolism; Thrombocytopenia

This article addresses the treatment of VTE disease.. We generated strong (Grade 1) and weak (Grade 2) recommendations based on high-quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence.. For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C).. Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences.

Topics: Administration, Oral; Anticoagulants; Diagnostic Imaging; Drug Administration Schedule; Evidence-Based Medicine; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Infusions, Intravenous; International Normalized Ratio; Long-Term Care; Polysaccharides; Pulmonary Embolism; Risk Factors; Societies, Medical; United States; Venous Thrombosis; Vitamin K

Patients with central nervous system (CNS) malignancies have a substantial risk for developing both thrombotic and bleeding disorders. The risk of venous thromboembolism (VTE) is substantially higher in these patients, both in the perioperative period and throughout their disease course. Patients with CNS malignancy harbor a latent hypercoagulability, which predisposes to VTE, as do postoperative immobility, hemiparesis, and other factors. The management of VTE in these patients is complex, given the significant morbidity and mortality associated with intratumoral hemorrhage. In the past, the perceived risk of intracranial hemorrhage limited the use of anticoagulation for the management of VTE with many favoring nonpharmacologic methods for prophylaxis and treatment. Inferior vena cava (IVC) filters have since lost favor at many centers given significant complications, which appear to be more frequent in patients with CNS malignancy. Recent studies have demonstrated safe and efficacious use of anticoagulation in these patients with a low incidence of intracranial hemorrhage. Treatment of established VTE is now recommended in this population with many centers favoring low-molecular-weight heparin (LMWH) versus oral warfarin for short- or long-term treatment. We advocate a multimodality approach utilizing compression stockings, intermittent compression devices, and heparin in the perioperative setting as the best proven method to reduce the risk of VTE. In the absence of a strict contraindication to systemic anticoagulation, such as previous intracranial hemorrhage or profound thrombocytopenia, we recommend LMWH in patients with newly diagnosed VTE and a CNS malignancy.

Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Arginine; Bevacizumab; Central Nervous System Neoplasms; Fondaparinux; Glioblastoma; Glioma; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Vena Cava Filters; Venous Thromboembolism; Venous Thrombosis; Warfarin

This study aims to investigate whether the usage of fondaparinux sodium may result in major hemorrhages following major orthopedic surgery.. Forty-three patients (30 females and 13 males; mean age 66 years; range 34 to 94 years) at the age of >18 years who were scheduled for major orthopedic surgery were included. Total hip arthroplasty, total knee arthroplasty and proximal femur fracture surgeries were defined as the major orthopedic surgeries. Prophylaxis was administered with 2.5 mg fondaparinux sodium once daily subcutaneously. Prophylaxis was initiated at 6-8 hours after the closure of incision. During the prophylaxis period (31±3 days), the patients were monitored for symptomatic deep venous thrombosis. Serum creatinine, platelet and hemoglobin levels were measured at the baseline and in the first week and at one month postoperatively. Wound healing time, healing complications, and major/minor hemorrhages seen during the prophylaxis period were recorded.. During the follow-up, none of the patients had symptomatic deep vein thrombosis or symptomatic pulmonary embolism. Two patients (4.6%) had delayed wound healing, while four (9.3%) had minor ecchymosis. No major hemorrhages were observed in any patients.. With the long-term use of fondaparinux, we did not observe any major hemorrhagic complications. However, further large-scale studies including control groups are required to establish the effects of long-term use of fondaparinux.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Fondaparinux; Humans; Injections, Subcutaneous; Male; Middle Aged; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Treatment Outcome; Venous Thrombosis

Due to high health care costs of venous thromboembolism (VTE), economic analyses are needed to determine the efficiency of different drug treatments. Consequently, a study was conducted to estimate the budgetary impact for the National Health System (NHS) with apixaban for prevention of venous thromboembolism (VTE) in total hip (THR) or knee (TKR) replacement.. Cost considered: the drugs for the prevention of VTE (apixaban, dabigatran, enoxaparin, fondaparinux, other heparins, rivaroxaban and warfarin) and the complications of VTE in the short term and in 5 years (deep vein thrombosis, pulmonary embolism, bleedings and the post-thrombotic syndrome). The effectiveness of prophylaxis was estimated using a meta-analysis. The VTE rates and death with apixaban are lower in THR and TKR than enoxaparin (-3.5% and -10.0%, respectively) with less bleeding events (-0.7% and -1.6%, respectively). Population data and unit costs were obtained from Spanish sources.. 5 years. All costs were discounted by 3.5% annually. Five years after commercialization, the use of apixaban was estimated to account for 23% of the prophylaxis of VTE and the use of enoxaparin decrease from the 60% to 33%.. Apixaban´s introduction for the prophylaxis of VTE would have a significant impact for the NHS, resulting in a saving of 547,422 Euro over a period of 5 years. In the case of outpatient administration of heparin did not have a cost, the savings for the NHS five years amount to 270,068 Euro.. According to this study, the introduction of apixaban may reduce the rate of VTE and bleeding compared with enoxaparin, decreasing the expenditure of NHS in VTE prophylaxis.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Budgets; Cost Control; Dabigatran; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Morpholines; Polysaccharides; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Spain; State Medicine; Thiophenes; Venous Thromboembolism

A 69-year-old woman presented to the emergency department with sudden onset of dyspnea. She reported bilateral total knee surgery 12 days prior for gonarthrosis. The patient was recommended low-molecular-weight heparin (LMWH) 0.4 cc (4 milliliter) twice a day. On evaluation, severe thrombocytopenia was detected. An echocardiogram was performed because of her dyspnea, which revealed right ventricular dilatation and hypokinesis. Due to suspicion of a pulmonary embolism (PE), a pulmonary computed tomography (CT) was performed, which revealed bilateral massive PE. This event occurred while the patient was receiving LMWH for prophylaxis of PE. Due to the presence of severe thrombocytopenia, fondaparinux and immunoglobulin were initiated. Her platelet levels improved significantly and she was discharged on warfarin.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Echocardiography; Female; Fondaparinux; Heparin; Humans; Immunoglobulin G; Polysaccharides; Pulmonary Embolism; Thrombocytopenia; Tomography, X-Ray Computed

Topics: Anticoagulants; Fondaparinux; Humans; Outcome Assessment, Health Care; Polysaccharides; Pulmonary Embolism; Research Design; Venous Thrombosis

A serious complication of heparin treatment, heparin-induced thrombocytopenia (HIT) is rarely observed in pregnant women. Drug therapy during pregnancy should always be chosen to minimize fetal risk. The management of HIT in pregnancy represents a medical challenge. Unlike heparins, the anticoagulants used in patients with HIT do cross the placenta, with unknown fetal effects.. We present a case of a 24-year-old female presenting for care at 34 weeks of gestation with acute pulmonary embolism treated initially with unfractionated heparin (UFH) and low molecular weight heparin (LMWH), who developed HIT. She was then successfully treated with fondaparinux.. To the best of our knowledge, this is one of the first case reports describing a successful use of fondaparinux in the treatment of HIT in a third-trimester pregnant woman, providing a novel approach for this subset of patients.

Topics: Female; Fondaparinux; Heparin; Humans; Polysaccharides; Pregnancy; Pulmonary Embolism; Thrombocytopenia; Ultrasonography; Young Adult

Many hospitalized Medical Service patients remain at high risk for venous thromboembolism (VTE) after hospital discharge. Our aim was to compare the effect of the use or omission of extended pharmacologic VTE prophylaxis after hospital discharge among Medical Service patients on the incidence of symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) over the ensuing 3 months.. In this case-control study, we identified a case population of 461 patients for whom parenteral pharmacological VTE prophylaxis was prescribed to continue after discharge and matched them according to age, sex, and VTE risk score to a control group of 922 patients for whom VTE prophylaxis was not continued after discharge.. The primary endpoint of symptomatic DVT or PE at 90 days occurred in 5.0% of patients receiving extended prophylaxis compared with 4.3% of patients who received no prophylaxis after discharge (P=.58). Fewer patients were alive at 90 days in patients receiving extended pharmacologic VTE prophylaxis, compared with those who received no prophylaxis after discharge (56.8% vs 68.4%, P <.001). Major bleeding, defined as those events requiring blood transfusion, medical, or surgical intervention, occurred more frequently in patients receiving extended VTE prophylaxis after discharge than in those patients who received no prophylaxis after discharge (3.9% vs 1.9%, P=.03).. Extended pharmacologic thromboprophylaxis in high-risk Medical Service patients did not reduce symptomatic DVT and PE in the ensuing 90 days after hospital discharge. There was a higher incidence of all-cause death and major bleeding episodes in patients receiving extended prophylaxis. Our observations do not support the routine use of extended VTE prophylaxis in Medical Service patients. Further research is needed to identify patients who may benefit from extended pharmacologic VTE prophylaxis and those who may have too great a bleeding risk.

Topics: Aged; Anticoagulants; Case-Control Studies; Confidence Intervals; Endpoint Determination; Enoxaparin; Female; Follow-Up Studies; Fondaparinux; Humans; Incidence; Male; Neoplasms; Patient Discharge; Polysaccharides; Pulmonary Embolism; Risk Factors; Treatment Outcome; Venous Thromboembolism

Clinical evidence demonstrating the effectiveness of pharmacological and mechanical thromboprophylaxis for the prevention of pulmonary embolism is limited because the prevalence of postoperative pulmonary embolism following total hip and knee arthroplasty is very low. Our purposes were to characterize a patient population with in-hospital pulmonary embolism, to identify perioperative risk factors associated with pulmonary embolism, and to analyze the effect of combining fondaparinux with mechanical prophylaxis on the prevalence of pulmonary embolism following total hip and knee arthroplasty.. We retrospectively identified 27,542 patients who underwent total hip or knee arthroplasty at 793 hospitals, using data from the Diagnosis Procedure Combination database, collected from July 1 to December 31 in 2007 and 2008. We extracted data on patient sex, age, primary diagnoses, and comorbidities that could potentially affect the prevalence of pulmonary embolism. The dates of pharmacological and mechanical thromboprophylaxis were identified for each patient. Logistic regression analysis was performed to analyze the concurrent effects of various factors on the prevalence of postoperative pulmonary embolism.. The mean age (and standard deviation) of the patients at the time of arthroplasty was 69.9 ± 10.3 years, and 23,783 patients (86.4%) were diagnosed as having osteoarthritis. The overall mean duration of anesthesia was 159 ± 84 minutes. The overall prevalence of postoperative pulmonary embolism was 0.55% (151 of 27,542). Significant risk factors for postoperative pulmonary embolism included age, number of comorbidities, diagnosis of rheumatoid arthritis, type of anesthesia, and duration of anesthesia. Multivariate analysis found that the prevalence of postoperative pulmonary embolism was significantly reduced when fondaparinux was used in combination with mechanical prophylaxis, compared with the use of mechanical prophylaxis alone (0.40% versus 0.66%; odds ratio, 0.60; 95% confidence interval, 0.42 to 0.84; p = 0.003).. These findings could help to identify patients at higher risk of postoperative pulmonary embolism after total hip or knee arthroplasty. Our results demonstrate the effectiveness of fondaparinux in combination with mechanical prophylaxis for the prevention of postoperative pulmonary embolism after total hip or knee arthroplasty.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cohort Studies; Confidence Intervals; Databases, Factual; Female; Follow-Up Studies; Fondaparinux; Humans; Incidence; Intermittent Pneumatic Compression Devices; Japan; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Osteoarthritis, Hip; Osteoarthritis, Knee; Polysaccharides; Postoperative Care; Postoperative Complications; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Stockings, Compression; Treatment Outcome

Hospitalized cancer patients are at an increased risk for venous thromboembolism (VTE) and it is recommended they receive pharmacologic prophylaxis unless otherwise contraindicated. The majority of data supporting this recommendation comes from sub-group analyses and extrapolation of data gathered in general medical/surgical patients. This study seeks to assess the safety and efficacy of VTE prophylaxis in cancer patients admitted to our institution.. Charts of patients 18-89 years of age receiving VTE prophylaxis with unfractionated heparin, low molecular weigh heparin, or fondaparinux while admitted to Karmanos Cancer Center between September and October 2007 were retrospectively reviewed. Risk factors for VTE were assessed and the efficacy/safety of the prophylactic agents was compared.. One-hundred and eighty consecutive patients were identified. The average number of risk factors for developing VTE was 3-4 per hospital admission in addition to an active cancer diagnosis. Three VTEs occurred in the heparin group with two patients experiencing a VTE during their admission and one experiencing a VTE within 1 month after discharge. Four (2.6%) patients receiving heparin had a major bleeding event. Minor bleeding occurred in 14.3, 11.5, and 22.2% of patients receiving heparin, enoxaparin, and fondaparinux, respectively.. This retrospective study showed cancer patients are at increased risk for VTE, typically with 3-4 risk factors per admission. VTEs were uncommon; however, three patients receiving heparin experienced a VTE and four had a major bleeding event. Minor bleeding rates were similar among groups.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Drug Therapy, Combination; Enoxaparin; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Medical Records; Middle Aged; Neoplasms; Polysaccharides; Practice Guidelines as Topic; Pulmonary Embolism; Retrospective Studies; Risk Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Young Adult

The purpose of this investigation is to show trends in the duration of hospitalization of patients with pulmonary embolism (PE) and deep venous thrombosis (DVT). The number of patients discharged from short-stay non-Federal hospitals throughout the United States with a primary diagnostic code for PE or DVT from 1979 through 2005 was obtained from the National Hospital Discharge Survey. By 2005, 13% of patients with PE were discharged in 1 to 2 days, 30% in 3 to 4 days, 26% in 5 to 6 days, and 31% in > or =7 days. Regarding DVT, by 2005, 26% of patients with DVT were discharged in 1 to 2 days, 34% were discharged in 3 to 4 days, 20% were discharged in 5 to 6 days, and 19% were discharged in > or =7 days. The data indicate that large proportions of patients with a primary diagnosis of PE and of DVT are being discharged before adequate heparin can be administered and before warfarin can become antithrombotic. Others have reported an increased mortality among patients with PE discharged in < or =4 days. If patients are to be discharged before adequate heparin can be administered, outpatient treatment with low-molecular-weight heparin (LMWH) for at least 5 days and until the international normalized ratio (INR) is > or =2.0 for 24 hours is recommended or extended outpatient treatment with LMWH may be considered.

Topics: Anticoagulants; Cost Savings; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Length of Stay; Patient Discharge; Patient Selection; Polysaccharides; Pulmonary Embolism; United States; Venous Thrombosis; Warfarin

Essential thrombocythemia is a hematological disorder characterized by clonal hemopoiesis in the bone marrow and increased number of circulating platelets. It is usually discovered accidentally at the time of routine blood examinations or can become clinically evident with either thrombotic or hemorrhagic complications. In the present article, we describe the case of a 66-year-old woman with pneumonia due to Pneumocystis carinii, who experienced deep vein thrombosis and pulmonary embolism during hospitalization with a subsequent heparin-induced thrombocytopenia. Bone marrow examination performed after clinical improvement revealed the patient to be affected by essential thrombocythemia.

Topics: Aged; Anticoagulants; Female; Fondaparinux; Heparin; Humans; Incidental Findings; Platelet Factor 4; Pneumonia, Pneumocystis; Polysaccharides; Pulmonary Embolism; Thrombocythemia, Essential; Thrombocytopenia; Thrombophlebitis; Warfarin

Approximately 50% of hospitalised patients need thromboprophylaxis. However, 30-50% of these high-risk patients remain without adequate treatment. Treatment of venous thrombombolism has remained unchanged, apart from the option of replacement of low-molecular-weight heparin by fondaparinux in the initial regimen. Practical guidance is now available for unfractionated heparin. Administration of thrombolysis is restricted to haemostatically unstable patients and local massive thrombosis, where catheter-based strategies are preferred to systemic fibrinolytics. Although anticoagulation therapy is life-long in the case of patients with idiopathic thrombosis and permanent risk factors, repeated safety evaluations must be performed. Otherwise, the duration of anticoagulation treatment is individualised.

Topics: Drug Administration Schedule; Fibrinolytic Agents; Fondaparinux; Humans; Polysaccharides; Pulmonary Embolism; Venous Thrombosis

Cardiopulmonary bypass during pregnancy is associated with a high fetal and maternal mortality. We report a successful pulmonary embolectomy in a woman at the 27th week of pregnancy; we performed surgical pulmonary embolectomy under cardiopulmonary bypass to restore adequate hemodynamic stability and to relieve right ventricle strain. We discuss the decision made for the preferred anticoagulation drug in the setting of heparin-induced thrombocytopenia in the gravida. The pregnancy was carried to term and she delivered a healthy boy at 38 weeks of gestation.

Topics: Adult; Anticoagulants; Cardiopulmonary Bypass; Echocardiography, Transesophageal; Embolectomy; Enoxaparin; Female; Fondaparinux; Heart Arrest, Induced; Heparin; Humans; Infant, Newborn; Live Birth; Male; Polysaccharides; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Second; Pulmonary Embolism; Thrombocytopenia; Tirofiban; Treatment Outcome; Tyrosine; Venous Thrombosis; Warfarin

Venous thromboembolism remains the most common cause of hospital readmission and death after total joint arthroplasty. The 2008 American College of Chest Physicians (ACCP) guidelines, based on prospective randomized clinical trials with a venography endpoint, endorse the use of low-molecular-weight heparin, fondaparinux, or adjusted dose warfarin (target international normalized ratio, 2.5; range, 2-3) for up to 35 days after total hip arthroplasty (THA) and total knee arthroplasty (TKA). In the past, the ACCP has recommended against the use of aspirin, graduated compression stockings, or venous compression devices as the sole means of prophylaxis, but in 2008 they first recommended the "optimal use of mechanical thromboprophylaxis with venous foot pumps or intermittent pneumatic compression devices" in patients undergoing total joint arthroplasty who "have a high risk of bleeding." When the high risk subsides, pharmacologic thromboprophylaxis is substituted for, or added to, mechanical methods. Fractionated heparins and pentasaccharide are the most effective agents in reducing venographic deep venous thrombosis (DVT) after total joint arthroplasty with residual clot rates <5% after THA and 20% after TKA, but major or clinically meaningful bleeding occurs in 3% to 5% of patients. Newer Xa and thrombin inhibitors enjoy greater efficacy with equal or higher bleeding rates. Low-intensity warfarin (target international normalized ratio, 2.0) combines safety (bleeding rates <1%) with efficacy (readmission for clinical DVT or pulmonary embolism 0.2%) after total joint arthroplasty. Warfarin represents a therapeutic compromise by preventing clinical events in exchange for a lower bleeding rate; genetic testing will likely simplify warfarin use and reduce outlier responders.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Chemoprevention; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Intermittent Pneumatic Compression Devices; Patient Readmission; Platelet Aggregation Inhibitors; Polysaccharides; Postoperative Hemorrhage; Practice Guidelines as Topic; Pulmonary Embolism; Venous Thrombosis; Warfarin

Topics: Anticoagulants; Clinical Trials, Phase III as Topic; Cost-Benefit Analysis; Fondaparinux; Humans; Off-Label Use; Polysaccharides; Pulmonary Embolism; United States; United States Food and Drug Administration; Venous Thrombosis

Topics: Anticoagulants; Cardiopulmonary Bypass; Embolectomy; Enoxaparin; Female; Fondaparinux; Heart Arrest, Induced; Heparin; Humans; Polysaccharides; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Second; Pulmonary Embolism; Risk Assessment; Thrombocytopenia; Tirofiban; Treatment Outcome; Tyrosine; Ultrasonography; Venous Thrombosis; Warfarin

Topics: Aged; Aged, 80 and over; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Humans; Male; Middle Aged; Pilot Projects; Polysaccharides; Pulmonary Embolism; Rehabilitation Centers; Retrospective Studies; Stroke Rehabilitation; Venous Thrombosis

In the initial treatment of venous thromboembolism (VTE) fondaparinux, a pentasaccharide, is a good alternative to heparin. Whether this is also true for cancer patients is unknown. We performed two post-hoc analyses of two randomized studies to compare efficacy, safety and overall survival of fondaparinux to standard initial (low-molecular-weight) heparin (LMWH) treatment in cancer patients with venous thromboembolism. Two hundred thirty-seven cancer patients with deep venous thrombosis (DVT) were initially treated with fondaparinux or enoxaparin. Two hundred forty cancer patients with pulmonary embolism (PE) received fondaparinux or unfractionated heparin. The initial treatment was followed by vitamin K antagonists. In DVT patients, the three-month recurrence rate was 5.4% in the enoxaparin recipients compared to 12.7% in those treated with fondaparinux [absolute difference 7.3%, 95% CI 0.1, 14.5]. A recurrence was observed in 8.9% of the PE patients treated with fondaparinux compared to 17.2% in the unfractionated heparin recipients [absolute difference -8.3, 95% CI -16.7, 0.1]. In both studies no difference in bleeding and overall survival was observed. Regarding overall survival and bleeding fondaparinux is comparable to enoxaparin and unfractionated heparin in cancer patients. No significant differences in recurrent VTE were observed when comparing fondaparinux with unfractionated or LMWH. Because of study limitations these results should be considered hypothesis-generating.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Double-Blind Method; Enoxaparin; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms; Polysaccharides; Proportional Hazards Models; Pulmonary Embolism; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Secondary Prevention; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis; Vitamin K; Young Adult

Fondaparinux is an antithrombotic agent with unique properties that may offer benefit to patients beyond the current approved indications. To explore the off-label use versus approved use of fondaparinux, we initiated a single-center registry of fondaparinux use. During the 25-month study period, 219 patients were prescribed fondaparinux: 157 (71.7%) for prophylaxis and 62 (28.3%) patients for the treatment of thrombosis. When fondaparinux was used for prophylaxis in our registry, 94% of patients had documentation of heparin-induced thrombocytopenia (HIT). Fondaparinux warrants further evaluation in patients with HIT or suspected HIT. In the meantime, its off-label use may exceed its use for FDA-approved indications.

Topics: Adult; Aged; Drug Prescriptions; Female; Fibrinolytic Agents; Fondaparinux; Heparin; Hospitals; Humans; Male; Middle Aged; Orthopedic Procedures; Perioperative Care; Polysaccharides; Pulmonary Embolism; Registries; Risk Factors; Thrombocytopenia; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Azetidines; Benzylamines; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Morpholines; Polysaccharides; Pulmonary Embolism; Research Design; Rivaroxaban; Thiophenes; Venous Thrombosis

This chapter about treatment for venous thromboembolic disease is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading, see "Grades of Recommendation" chapter). Among the key recommendations in this chapter are the following: for patients with objectively confirmed deep vein thrombosis (DVT) or pulmonary embolism (PE), we recommend anticoagulant therapy with subcutaneous (SC) low-molecular-weight heparin (LMWH), monitored IV, or SC unfractionated heparin (UFH), unmonitored weight-based SC UFH, or SC fondaparinux (all Grade 1A). For patients with a high clinical suspicion of DVT or PE, we recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests (Grade 1C). For patients with confirmed PE, we recommend early evaluation of the risks to benefits of thrombolytic therapy (Grade 1C); for those with hemodynamic compromise, we recommend short-course thrombolytic therapy (Grade 1B); and for those with nonmassive PE, we recommend against the use of thrombolytic therapy (Grade 1B). In acute DVT or PE, we recommend initial treatment with LMWH, UFH or fondaparinux for at least 5 days rather than a shorter period (Grade 1C); and initiation of vitamin K antagonists (VKAs) together with LMWH, UFH, or fondaparinux on the first treatment day, and discontinuation of these heparin preparations when the international normalized ratio (INR) is > or = 2.0 for at least 24 h (Grade 1A). For patients with DVT or PE secondary to a transient (reversible) risk factor, we recommend treatment with a VKA for 3 months over treatment for shorter periods (Grade 1A). For patients with unprovoked DVT or PE, we recommend treatment with a VKA for at least 3 months (Grade 1A), and that all patients are then evaluated for the risks to benefits of indefinite therapy (Grade 1C). We recommend indefinite anticoagulant therapy for patients with a first unprovoked proximal DVT or PE and a low risk of bleeding when this is consistent with the patient's preference (Grade 1A), and for most patients with a second unprovoked DVT (Grade 1A). We recommend that the dose of VKA be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations (Grade 1A). We recommend at

Topics: Drug Therapy, Combination; Evidence-Based Medicine; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Injections, Intravenous; Injections, Subcutaneous; International Normalized Ratio; Polysaccharides; Pulmonary Embolism; Risk Assessment; Venous Thrombosis; Vitamin K

Heparin-induced thrombocythopenia (HIT) is a potentially serious complication of heparin treatment, rarely observed in cardiological wards. We present a case of a 38-year-old woman with dilated cardiomyopathy and massive pulmonary embolism treated with alteplase and unfractionated heparin. On 12th day an unexpected fall in platelet count was observed, without new signs of thrombosis. The HIT type II was diagnosed. Patient was treated effectively and safely by 7.5 mg of fondaparinux given subcutaneously once daily for 10 days.

Topics: Adult; Anticoagulants; Cardiomyopathy, Dilated; Female; Fondaparinux; Heparin; Humans; Injections, Subcutaneous; Polysaccharides; Pulmonary Embolism; Thrombocytopenia

Topics: Ambulatory Care; Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Outpatients; Polysaccharides; Pulmonary Embolism; Venous Thrombosis

Topics: Anticoagulants; Fondaparinux; Humans; Polysaccharides; Pulmonary Embolism

Initial treatment of venous thromboembolic events is currently based on antithrombotics. This treatment is validated and identical for deep vein thrombosis (DVT) and pulmonary embolism. For distal DVT, this treatment has still to be validated. This reference therapeutic strategy is firstly parenteral and based on low-molecular-weight heparins (LMWH) or fondaparinux, subcutaneously prescribed at fixed dosage based on body weight without any systematic dose adjustment on hemostasis tests. Unfractionated heparin is steel the reference treatment in case of severe renal insufficiency. This parenteral treatment has to be relieved by vitamin K antagonists (VKA). VKA has to be co-administrated for at least 3 days, without any loading dose and can be early initiated. VKA dose needs to be adjusted in order to maintain INR between 2 and 3. However, in case of cancer, LMWH have to be carried on for 6 months. A part this antithrombotic treatment, thrombolytics are recommended in case of massive PE and vena cava filter should be used in case of recurrence despite adequate antithrombotic treatment or in case of contraindication to antithrombotic.

Topics: Anticoagulants; Antifibrinolytic Agents; Factor X; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Injections, Intravenous; Injections, Subcutaneous; International Normalized Ratio; Polysaccharides; Pulmonary Embolism; Renal Insufficiency; Thromboembolism; Vena Cava Filters; Venous Thrombosis; Vitamin K

Treatment of thrombosis in children with end-stage renal disease (ESRD) is extremely challenging owing to the underlying risk of bleeding. Fondaparinux (Arixtra, Sanofi-Synthélabo), a synthetic pentasaccharide, is contraindicated in patients with compromised renal function as it is excreted via kidneys. We describe a unique case with ESRD and pulmonary embolism who was treated with fondaparinux owing to the toxicity and poor compliance with low-molecular-weight heparin. Despite regular hemodialysis, a gradual rise in drug levels was observed without significant bleeding complications. This report implies that although low dose fondaparinux can be an option in patients with ESRD under special circumstances, guidelines for laboratory monitoring and appropriate dose adjustments are urgently required to ensure the safety of the patient.

Topics: Adolescent; Anticoagulants; Female; Fondaparinux; Humans; Kidney Failure, Chronic; Polysaccharides; Pulmonary Embolism; Renal Dialysis

Topics: Adult; Anticoagulants; Cortisone; Drug Eruptions; Female; Fibrinolytic Agents; Follow-Up Studies; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Injections, Subcutaneous; Nadroparin; Ointments; Polysaccharides; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pulmonary Embolism

Topics: Anticoagulants; Factor X; Fondaparinux; Humans; Myocardial Infarction; Partial Thromboplastin Time; Polysaccharides; Pulmonary Embolism; Risk; Venous Thrombosis

43 years old women with tumor of the right ventricle was admitted to ICU due to pulmonary embolism and suspicion for heparin-induced thrombocytopenia. Thrombocytopenia was successfully treated with Arixtra and the patient was qualified for the cardio surgery intervention. Heparin is widely used in treatment and prophylaxis of venous thromboembolism and other diseases. One of the most important adverse effect of treatment with heparin is heparin-inducted thrombocytopenia (HIT), which is one of the most frequent drug-induced, immune-mediated type of thrombocytopenia. If it is unrecognized is associated with significant morbidity and mortality. According to our knowledge this is first report of Arixtra usage in patient with suspicion of HIT in Poland.

Topics: Adult; Anticoagulants; Female; Fondaparinux; Heart Neoplasms; Heart Ventricles; Heparin; Humans; Poland; Polysaccharides; Pulmonary Embolism; Thrombocytopenia; Warfarin

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost Savings; Cost-Benefit Analysis; Decision Making; Denmark; Drug Costs; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Humans; Models, Economic; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Risk Factors; Venous Thrombosis

Topics: Fibrinolytic Agents; Fondaparinux; Heparin; Humans; Infusions, Intravenous; Partial Thromboplastin Time; Polysaccharides; Pulmonary Embolism

Topics: Adult; Age Factors; Aged; Anticoagulants; Azetidines; Benzylamines; Dalteparin; Female; Fibrinolytic Agents; Fondaparinux; Humans; Male; Middle Aged; Multicenter Studies as Topic; Oligosaccharides; Placebos; Polysaccharides; Prodrugs; Pulmonary Embolism; Randomized Controlled Trials as Topic; Thromboembolism; Thrombomodulin; Time Factors; Warfarin

Topics: Adult; Aerospace Medicine; Anticoagulants; Death, Sudden; Female; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Life Style; Male; Obesity; Polysaccharides; Pulmonary Embolism; Smoking; Venous Thrombosis

Topics: Anticoagulants; Clinical Trials as Topic; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Heparin; Humans; Polysaccharides; Pulmonary Embolism; Risk Factors; Thrombophlebitis; Time Factors

Topics: Angina, Unstable; Anticoagulants; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Postoperative Complications; Pulmonary Embolism; Thromboembolism; Venous Thrombosis