fondaparinux and Venous-Thrombosis

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

Fondaparinux is a synthetic heparin pentasaccharide with a sequence identical to that found in anticoagulant heparin. It is a pure compound with a molecular weight of 1728Da. Fondaparinux catalyzes the conformational change of a serpin or serine protease inhibitor antithrombin III to accelerate the suicidal inactivation of factor Xa over 340-fold, which in turn inhibits thrombin generation in the coagulating signal transduction pathway. Fondaparinux does not inhibit thrombin activity, release tissue factor pathway inhibitor, or possess other properties of heparin such as anti-inflammatory, anti-viral, anti-angiogenesis, anti-neoplastic, and anti-metastatic effects though high affinity interactions with a variety of proteases, protease inhibitors, chemokines, cytokines, growth factors, and their respective receptors. Low antithrombin III levels in blood circulation also affects the efficacy of Fondaparinux. Thus, Fondaparinux represents a refined use of the anti-factor Xa property of heparin. As an anti-factor Xa drug, Fondaparinux has complete bioavailability subcutaneously, instant onset of action, a half-life of 15-20h, and a direct renal excretion without any metabolism. Fondaparinux has been shown to be superior to low molecular weight heparin in preventing deep vein thrombosis. Clinically, Fondaparinux is used for the prevention of deep vein thrombosis in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and pulmonary embolism with limitations of use in elderly, low weight, renal impaired patients and in those receiving spinal anesthesia. Clinical studies showed that Fondaparinux acts in prevention and treatment of venous thromboembolism and in ischemic heart disease without significant risk of bleeding.

Topics: Clinical Trials as Topic; Fondaparinux; Heparin; Humans; 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

Portal vein thrombosis (PVT) is a rare but serious complication in the decompensated stage of cirrhosis, and recurrent upper gastrointestinal bleeding and refractory ascites can occur in such patients. In decompensated cirrhotic patients, the application of conventional anticoagulant therapy is limited due to severe coagulation disorders, thrombocytopenia, and history of gastrointestinal bleeding.In this study, we sought to investigate the effect of fondaparinux on acute PVT in decompensated cirrhotic patients.Patients were treated with fondaparinux (2.5 mg, q 24 h, subcutaneously) in the region of the umbilicus for conventional liver protection, after a clear diagnosis was made and contraindications such as active bleeding were ruled out. Other anticoagulants and circulation-improving drugs were not administered. Platelet count, prothrombin time, international normalized ratio, D dimer (DD), and liver function were measured. Furthermore, portal vein color Doppler ultrasound was performed every 7 days while patients were treated with fondaparinux and after portal vein recanalization.The portal vein was recanalized in all patients after treatment (P = .018). The decline in DD had a predictive value for portal vein recanalization (P = .018). No side effects such as bleeding or thrombocytopenia occurred in any of the patients (P > .05).Selective factor Xa inhibitor fondaparinux is effective and safe for acute PVT in decompensated cirrhotic patients.

Topics: Adult; Aged; Factor Xa Inhibitors; Female; Fibrin Fibrinogen Degradation Products; Fondaparinux; Humans; International Normalized Ratio; Liver Cirrhosis; Male; Middle Aged; Platelet Count; Polysaccharides; Portal Vein; Predictive Value of Tests; Prothrombin Time; Treatment Outcome; Ultrasonography, Doppler; Vascular Surgical Procedures; Venous Thrombosis

Standard treatment of deep vein thrombosis (DVT) is based on antithrombotic therapy, initially with parenteral administration of unfractionated heparin or low molecular weight heparins (LMWH) for five to seven days, then subsequent long-term therapy with oral vitamin K antagonists (e.g. warfarin). Pentasaccharides are novel anticoagulants that may be favourable over standard therapy due to their predictable effect, no need for frequent monitoring or re-dosing, and few known drug interactions. Heparin-induced thrombocytopenia, a harmful effect of heparins, appears to be rare during treatment with pentasaccharides.. To assess the efficacy and harms of pentasaccharides for the treatment of deep vein thrombosis.. The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (22 March 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2) (searched 22 March 2017). We searched clinical trials databases for details of ongoing or unpublished studies and the reference lists of relevant articles for additional citations.. We included randomised controlled trials in which people 18 years of age or older with a DVT confirmed by standard imaging techniques were allocated to receive a pentasaccharide (fondaparinux, idraparinux, or idrabiotaparinux) for the treatment of DVT in comparison with standard therapy or other treatments.. We extracted data characterising the included trials according to the methods, participants, interventions, and outcomes. We assessed risk of bias using Cochrane's 'Risk of bias' tool and employed the GRADE methodology to evaluate the quality of the evidence.The main primary outcome for efficacy was recurrent venous thromboembolism (VTE), and the main primary outcome for harm was major and clinically relevant bleeding. Since our outcomes were dichotomous, we calculated the risk ratio (RR) with a 95% confidence interval (CI). We combined the effects of different comparisons through a meta-analysis using a fixed-effect model.. We included five randomised controlled trials of 6981 participants comparing pentasaccharides with standard therapy or other pentasaccharides. The quality of the evidence varied depending on the outcome and was judged as of moderate to very low quality. We downgraded the quality of the evidence due to risk of bias or imprecision, or both.Two studies evaluated fondaparinux, at doses of 5.0 mg, 7.5 mg, and 10.0 mg, plus vitamin K antagonist in comparison with standard therapy. A meta-analysis of these two studies showed no clear difference in the risk of recurrent VTE (RR 0.80, 95% CI 0.43 to 1.47; 2658 participants); moderate-quality evidence. The frequencies of major bleeding were similar between interventions in the initial period of treatment (approximately five days) (RR 1.15, 95% CI 0.39 to 3.44; 2645 participants) and at three months' follow-up (RR 1.05, 95% CI 0.64 to 1.71; 2645 participants). We judged the quality of the evidence as moderate.One study (757 participants) compared idrabiotaparinux (3.0 mg) with idraparinux (2.5 mg) and demonstrated no clear difference in the risk of recurrent VTE at six months' follow-up (RR 0.72, 95% CI 0.31 to 1.69); low-quality evidence. Major bleeding during the initial treatment period was not reported. Major bleeding at six-month follow-up was less frequent in participants receiving idrabiotaparinux versus participants treated with idraparinux (RR 0.21, 95% CI 0.06 to 0.71); low-quality evidence.The effect of an initial treatment with LMWH followed by three months of idraparinux (10 mg) showed no clear difference from standard therapy for risk of recurrent VTE (RR 1.51, 95% CI 0.26 to 8.90; 263 participants); very low-quality evidence; one study. Major bleeding during the initial treatment period was not reported. The frequency of major and other clinically relevant bleeding at three months' follow-up ranged from 2% to 15% in participants receiving LMWH and increasing doses of idraparinux of 2.5 mg, 5 mg, 7.5 mg, or 10 mg. When dosage groups were combined, there was no clear difference in major plus other clinically relevant bleeding or in major bleeding alone between the idraparinux treatment group and the standard therapy group (RR 1.30, 95% CI 0.70 to 2.40; 659 participants; RR 3.76, 95% CI 0.50 to 28.19; 659 participants, respectively); very low-quality evidence.One study (2904 participants) compared idraparinux (2.5 mg) to standard therapy. There was no clear difference in the risk of recurrent VTE at thre. We found moderate-quality evidence that the effects of fondaparinux at doses of 5.0 mg, 7.5 mg, and 10.0 mg plus vitamin K antagonist are similar in terms of recurrent VTE and risk of major bleeding compared with standard treatment for DVT.Low-quality evidence suggests equal efficacy of idraparinux at 2.5 mg and the equimolar dose of 3.0 mg of idrabiotaparinux with regard to recurrent VTE, but a higher frequency of major bleeding was observed in participants treated with idraparinux.We judged evidence on the effectiveness of idraparinux compared with standard therapy, with or without initial treatment with LMWH, and on associated bleeding risk to be low to very low quality, therefore we have very limited confidence in the estimated effects.The observed similar effectiveness in terms of recurrent DVT and harmful effects in terms of bleeding risk with fondaparinux plus vitamin K antagonist compared to standard treatment for DVT suggest that it may be an alternative to conventional anticoagulants for the treatment of DVT in certain circumstances.

Topics: Anticoagulants; Biotin; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Oligosaccharides; Polysaccharides; Randomized Controlled Trials as Topic; Recurrence; Time Factors; Venous Thrombosis

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

Pharmacologic prophylaxis of deep vein thrombosis and venous thromboembolism (VTE) is an important aspect of medical care, particularly in the inpatient setting. Low-molecular weight heparins, heparin, and fondaparinux are commonly used agents to prevent VTE, each of which has well established dosing regimens in patients with normal body mass index. Dosing of these medications in morbidly obese populations (BMI > 40 kg/m(2)) is not as clearly defined in guidelines. This article reviews published data to support specific dosing regimens and monitoring strategies of these agents in this population. The most validated parenteral agent to prevent VTE in morbidly obese hospitalized patients is enoxaparin, dosed at 40 mg subcutaneously (SC) twice daily. If unfractionated heparin is utilized for prophylaxis in morbidly obese patients, a dose of 7500 units SC three times daily should be considered. Monitoring of anti-factor Xa levels to guide prophylactic dosing is an option, although the utility of this lab test is limited, as target anti-Xa ranges for VTE prophylaxis have not been universally defined and trials have not shown a clear link between anti-factor Xa levels and bleeding or thrombotic events. Additional studies are needed to clearly define the most appropriate dosing strategies in patients with moderate obesity (BMI 35-40 mg/m(2)) and those with extreme obesity (BMI > 60 mg/m(2)).

Topics: Factor Xa; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Obesity, Morbid; Polysaccharides; Venous Thromboembolism; Venous Thrombosis

Venous thromboembolism (VTE) is a common and potentially fatal disease. Fondaparinux is a synthetic agent able to act on single factors involved in the coagulation network, which could be administered at fixed doses and with a more predictable response.. This review will focus on the efficacy and safety of fondaparinux in the treatment of major VTE (deep vein thrombosis and pulmonary embolism) and in the treatment of superficial vein thrombosis (SVT).. Results of high quality randomized controlled trials have clearly shown the efficacy and safety of fondaparinux in comparison to conventional treatment in patients with a major VTE. There are limited evidences on the safety and efficacy of different options in patients presenting with SVT. Fondaparinux has been evaluated in a large population of patients presenting with a SVT. Results of this high quality RCT provided the evidence on the efficacy and safety of fondaparinux 2.5 mg s.c./day for 45 days in this setting. Thus, considering the evidence of the literature and thanks to its pharmacokinetic and pharmacodynamic characteristics, fondaparinux represent a valid treatment option for both the acute management of patients with major VTE, and for the treatment of SVT.

Topics: Anticoagulants; Fondaparinux; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Venous Thromboembolism; Venous Thrombosis

Venous thromboembolism (VTE) is a common condition with potentially serious and life-threatening consequences. The standard method of thromboprophylaxis uses an anticoagulant such as low molecular weight heparin (LMWH) or warfarin. In recent years, another type of anticoagulant, pentasaccharide, an indirect factor Xa inhibitor, has shown good anticoagulative effect in clinical trials. Three types of pentasaccharides are available: short-acting fondaparinux, long-acting idraparinux and idrabiotaparinux. Pentasaccharides cause little heparin-induced thrombocytopenia and are better tolerated than unfractionated heparin, LMWH and warfarin. However, no consensus has been reached on whether pentasaccharides are superior or inferior to other anticoagulative methods.. To assess effects of pentasaccharides versus other methods of thromboembolic prevention (thromboprophylaxis) in people who require anticoagulant treatment to prevent venous thromboembolism.. The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched March 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2). The CIS searched trial databases for details of ongoing and unpublished studies. Review authors searched LILACS (Latin American and Caribbean Health Sciences) and the reference lists of relevant studies and reviews identified by electronic searches.. We included randomised controlled trials on any type of pentasaccharide versus other anticoagulation methods (pharmaceutical or mechanical) for VTE prevention.. Two review authors independently selected trials, assessed methodological quality and extracted data in predesigned tables.. We included in this review 25 studies with a total of 21,004 participants. All investigated fondaparinux for VTE prevention; none investigated idraparinux or idrabiotaparinux. Studies included participants undergoing abdominal surgery, thoracic surgery, bariatric surgery or coronary bypass surgery; acutely ill hospitalised medical patients; people requiring rigid or semirigid immobilisation; and those with superficial venous thrombosis. Most studies focused on orthopaedic patients. We lowered the quality of the evidence because of heterogeneity between studies and a small number of events causing imprecision.When comparing fondaparinux with placebo, we found less total VTE (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.15 to 0.38; 5717 participants; 8 studies; I. Moderate to high quality evidence shows that fondaparinux is effective for short-term prevention of VTE when compared with placebo. It can reduce total VTE, DVT, total PE and symptomatic VTE, and does not demonstrate a reduction in deaths compared with placebo. Low to moderate quality evidence shows that fondaparinux is more effective for short-term VTE prevention when compared with LMWH. It can reduce total VTE and total DVT and does not demonstrate a reduction in deaths when compared with LMWH. However, at the same time, moderate to high quality evidence shows that fondaparinux increases major bleeding when compared with placebo and LMWH. Therefore, when fondaparinux is chosen for the prevention of VTE, attention should be paid to the person's bleeding and thrombosis risks. Most data were derived from patients undergoing orthopaedic surgery. Therefore, the conclusion predominantly pertains to these patients. Data on fondaparinux for other clinical conditions are sparse.

Topics: Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Venous Thromboembolism; Venous Thrombosis; Warfarin

Superficial vein thrombosis (SVT) was considered to be a benign and self-limiting condition. However, it is now appreciated that a significant proportion of those presenting with SVT will have concomitant deep vein thrombosis or pulmonary embolism, or are at significant risk of developing deep venous thromboembolism. Potential therapeutic options include topical preparations, compression therapy (stockings, bandages), medication such as non-steroidal anti-inflammatory drugs (NSAIDs) or anticoagulants (therapeutic or prophylactic doses) and surgery, ligation or stripping, of superficial veins. The treatment of choice is therapeutic/intermediate dose low molecular weight heparin or prophylactic dose fondaparinux administered for 4-6 weeks. The cost-effectiveness of treatment is a concern and more targeted therapy is required.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Risk Factors; Time Factors; 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 introduction of venography into patient care was a major advance because it was the first accurate method for the diagnosis of DVT. Compression ultrasound has since become the preferred test for patients with suspected DVT because, unlike venography, it is simple, non-invasive and widely available. Venography has facilitated the development and approval of new anticoagulants and remains widely used as an efficacy outcome in trials of venous thromboembolism prevention. Most thrombi detected by screening venography are, however, small and unimportant for patients. In order to calculate the trade-off between an asymptomatic thrombus and a bleed we require an estimate of the number of asymptomatic thrombi that must be prevented to avoid a patient-important thrombus. A credible estimate of this ratio is not available. Therefore when used as a measure of efficacy in trials of thromboprophylaxis, venography has limitations for comparing the relative effects of alternative antithrombotic agents on outcomes important to patients.

Topics: Anticoagulants; Cardiology; Clinical Trials as Topic; Contrast Media; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Phlebography; Polysaccharides; Reproducibility of Results; Thrombosis; Treatment Outcome; Venous Thrombosis

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

Topics: Antibodies; Anticoagulants; Antithrombins; Arthroplasty, Replacement, Knee; Chondroitin Sulfates; Dermatan Sulfate; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Immunoglobulin G; Male; Middle Aged; Platelet Activation; Platelet Count; Platelet Factor 4; Polysaccharides; Practice Guidelines as Topic; Thrombocytopenia; Venous Thrombosis; Vitamin K

Drugs that inhibit factor Xa have been shown to reduce mortality and morbidity in acute coronary syndromes (ACS). Presently, factor Xa inhibition is most often achieved indirectly with the heparins and, increasingly, fondaparinux. Despite effective anticoagulation with indirect factor Xa inhibition there remains considerable mortality and morbidity in ACS. The recently developed direct factor Xa inhibitors (the xabans) appear to offer promise as alternatives to the heparins. We review the evidence behind indirect and direct factor Xa inhibition in non-ST-segment elevation ACS, ST-segment elevation myocardial infarction, and with percutaneous coronary intervention.

Topics: Acute Coronary Syndrome; Anticoagulants; Blood Coagulation; Factor Xa Inhibitors; Female; Fondaparinux; Heart Conduction System; Heparin; Humans; Male; Polysaccharides; Randomized Controlled Trials as Topic; Venous Thrombosis

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

The Authors describe diagnosis, treatment and therapy of deep venous thrombosis in Emergency Department following the last guidelines indications.. Deep venous thrombosis of the legs, ranges from asymptomatic, incidentally discovered emboli to massive embolism causing immediate death. Chronic sequelae of venous thromboembolism (deep venous thrombosis and pulmonary embolism) include the post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension. Acute pulmonary embolism may occur rapidly and unpredictably and may be difficult to diagnose. Diagnosis and treatment can reduce the risk of death, and appropriate primary prophylaxis is usually effective. Patients treated for acute pulmonary embolism appear to be more times as likely to die of recurrent thromboembolism in the next year.

Topics: Anticoagulants; Antifibrinolytic Agents; Emergency Medical Services; Emergency Service, Hospital; Fibrin Fibrinogen Degradation Products; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Risk Factors; Stockings, Compression; Thrombectomy; Thromboembolism; Thrombolytic Therapy; Tomography, Spiral Computed; Ultrasonography; Vena Cava Filters; Venous Thrombosis; Vitamin K

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

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

The prevalence of obesity has increased substantially over recent years. Clinicians are increasingly being challenged with making uncertain anticoagulant dosing decisions, as the optimal dosing strategy for most anticoagulants in the obese patient population remains unknown. Research published to date suggests that the clearance of anticoagulants increases with weight. As obesity is associated with an increased risk of venous thromboembolism and arterial disease, there is an urgent need to establish appropriate anticoagulation regimens for this patient group. Research studies applying the method of pharmacokinetic-pharmacodynamic modelling and simulation could establish an appropriate evidence base and provide direction and reassurance to prescribing clinicians.

Topics: Acute Coronary Syndrome; Anticoagulants; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Double-Blind Method; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Humans; Morpholines; Multicenter Studies as Topic; Obesity; Polysaccharides; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thrombin; Thrombophilia; Venous Thrombosis; Warfarin

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

Currently, pharmacological thromboprophylaxis is frequently required in patients undergoing surgery, due to the high risk of deep venous thrombosis in the perioperative period. The administration of these anticoagulant agents (in Spain, usually low molecular weight heparins or fondaparinux, and in future, probably also the new oral anticoagulants dabigatran and rivaroxaban) may conflict with regional anesthetic techniques, in which maintaining hemostatic integrity is essential. Therefore, safety protocols have been designed that allow thromboprophylaxis to be administered with optimal effectiveness and anesthetic techniques to be performed with maximal safety; these protocols are based on the drug used, as well as on the dose and time of administration. The present chapter reviews the details related to these issues.

Topics: Acenocoumarol; Administration, Oral; Anesthesia, Conduction; Anticoagulants; Benzimidazoles; Clinical Protocols; Dabigatran; Early Ambulation; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Morpholines; Polysaccharides; Postoperative Complications; Pyridines; Risk Factors; Rivaroxaban; Safety; Surgical Procedures, Operative; Thiophenes; Venous Thromboembolism; Venous Thrombosis

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

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Arthroscopy; Drug Administration Schedule; Fondaparinux; Hematoma, Epidural, Spinal; Hematoma, Subdural, Spinal; Heparin; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Premedication; Punctures; Soft Tissue Injuries; Thromboembolism; Venous Thrombosis; Wounds and Injuries

Cancer is a risk factor for venous thromboembolism (VTE). This risk is amplified by treatment with chemotherapy, radiation, or surgery. Thus, patients with cancer undergoing major surgery should receive appropriate prophylaxis. Available agents include low-dose unfractionated heparin (LDUH), low-molecular-weight heparin (LMWH), and Factor Xa inhibitors. Recent data suggest that Factor Xa inhibitors are safe and effective for VTE prevention in patients with cancer undergoing abdominal surgery. Further study in this patient population is warranted.

Topics: Abdomen; Anticoagulants; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; Neoplasms; Polysaccharides; Postoperative Complications; Risk Factors; Venous Thrombosis

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

Thromboembolic complications are one of the most severe complications after orthopaedic or trauma surgery. More than 50% of patients undergoing total knee replacement are at risk of suffering deep-vein thrombosis if not provided sufficient prophylaxis. The former standard prophylaxis with unfractionated heparin has been changed over the few last years to low molecular weight heparin or heparinoids, due to the increased incidence of heparin-induced thrombocytopenia under therapy with unfractionated heparin. Risk management is based on different risk levels: highest risk, high risk, intermediate risk and low risk. The probabilities of suffering from deep-vein thrombosis have been determined dependent on the risk level. In patients with total knee replacement, which are at highest risk, a higher dose for the prevention of thromboembolism has been recommended. The synthetic, selective antithrombin-binding pentasaccharide fondaparinux has been successfully used in prophylaxis for the prevention of thrombosis in highest risk patients. However, because of a higher risk of bleeding, this pentasaccharide can be only given 6-8 h after surgery. Low molecular weight heparins and the pentasaccharide are the standard pharmacological prophylaxis for the prevention of venous thromboembolism. Physical therapy, pneumatic compression, A-V impulse systems, passive ankle motion systems and graduated compression stockings are an additional, effective prophylaxis without side effects.

Topics: Adult; Age Factors; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Orthopedic Procedures; Physical Therapy Modalities; Polysaccharides; Postoperative Complications; Risk Assessment; Risk Factors; Stockings, Compression; Thrombocytopenia; Thromboembolism; Time Factors; Venous Thrombosis

Fondaparinux is the first selective inhibitor of the coagulation factor Xa which is commercially avaliable for clinical use. It has been approved for the prevention of venous thromboembolism in patients undergoing orthopedic surgery and for the initial therapy of venous thromboembolism. In randomized clinical trials the value of fondaparinux in the treatment of ST-elevation myocardial infarction (STEMI) has been investigated. The PENTALYSE study showed that fondaparinux was at least as effective and safe as unfractionated heparin in 333 patients with STEMI undergoing fibrinolysis with t-PA. In the recent large OASIS-6 trial with 12,092 patients the treatment with 2.5 mg fondaparinux daily significantly reduced death and reinfarctions until day 30 compared with guideline recommended usual care and compared with unfractionated heparin (9.7% vs 11.2%, p = 0.008) without increasing major bleedings (1.0% vs 1.3%, p = 0.13). This advantage was predominantly seen in the subgroups of patients with fibrinolysis and without early reperfusion therapy. However, in the subgroup of primary percutaneous coronary interventions (PCIs) no clinical benefit of fondaparinux was found, but there were more catheter thrombosis and acute thrombotic complications. In summary, fondaparinux is a new antithrombin that is an efficient, safe, and easy to use in treatment for STEMI patients, particularly those not undergoing primary PCI.

Topics: Acute Coronary Syndrome; Anticoagulants; Fondaparinux; Heparin; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Venous Thrombosis

Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism, remains a common and costly condition that is associated with significant morbidity and mortality. Treatment options for initial management of DVT include unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), and fondaparinux, which is the first of a new class of pentasaccharide antithrombotic agents with anti-factor Xa activity. LMWHs are an important tool in DVT management, offering advantages over UFH such as ease of dosing, lack of need for coagulation monitoring, and reduced risk for heparin-induced thrombocytopenia (HIT). Fondaparinux is also characterized by a simple dosing regimen, no need for coagulation monitoring, and potentially a lower risk of HIT compared with LMWH. In a recent clinical trial of DVT management, efficacy and bleeding rates with fondaparinux appeared similar to those observed with LMWH. In contrast to LMWH, fondaparinux is generally given as a fixed dose across a range of patient weights rather than calculated per individual patient weight. Given the increasing economic burden of VTE, particularly due to its increased rate among the elderly, pharmacoeconomic analyses have become a particularly useful tool to aid in selecting among similarly effective and safe agents for VTE treatment. A recent cost-effective analysis demonstrated that fondaparinux use offers an attractive economic alternative to other agents for initial DVT therapy that could yield cost savings without compromising clinical outcomes or patient safety.

Topics: Anticoagulants; Enoxaparin; Fondaparinux; Humans; Polysaccharides; Venous Thrombosis

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

Hospital-acquired deep vein thrombosis (DVT) affects 10-25% of medical patients and up to 60% of surgical patients. While thromboprophylaxis is without a doubt under utilized in the hospital setting, there is also a need for more efficacious agents. Fondaparinux, the first of a new class of agents Factor Xa inhibitiors, has recently come into clinical use. It is a synthetic pentasaccharide and indirect Factor Xa inhibitor with a predictable antithrombotic action. Being a synthetic product, there are no concerns about supply, nor viral or prion protein contamination. Initial large international trials in orthopaedic patients demonstrated its superior efficacy to standard thromboprophylaxis. Further trials confirmed its superior efficacy in venous thromboembolism (VTE) prevention, both in medical and surgical patient groups, as well as treatment of pulmonary embolism and DVT. Its use has also recently been evaluated in acute coronary syndromes and angioplasty. Fondaparinux currently has licenses in the UK for thromboprophylaxis and treatment of VTE and a license for the management of acute coronary syndrome is likely to be forthcoming. It has a favourable side effect profile and if the price is acceptable, is likely to take over from low molecular weight heparins in these indications as the drug of choice on the grounds of efficacy and safety.

Topics: Anticoagulants; Antithrombin III; Coronary Disease; Fondaparinux; Humans; Polysaccharides; Thrombosis; 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

The incidence of venous thromboembolism in orthopaedic patients is high and its prevention deserves special attention. In patients with total hip and knee replacements and with the proximal femur fractures, low molecular weight heparin should be administered at higher prophylactic dosages. Following its approval, pentasaccharide (fondaparinux) should become the drug of choice, especially in patients with proximal femur fractures. Pharmacological prophylaxis should take at least 10 days in case of total knee replacements and longer in patients with increased risk of venous thromboembolism. In patients with total hip replacements or with proximal femur fractures, LMWH or pentasaccharide prophylaxis is indicated over a period of 28-35 days. Under the conditions of well working infrastructure for anticoagulation treatment, there is an alternative of warfarin treatment, lasting consequently 6-8 weeks. In patients with proximal femur fracture that bleed or are in a very increased risk of bleeding, a possible alternative is represented by intermittent pneumatic compression and shift to antithrombotic treatment after bleeding stops. In patients with knee arthroscopies displaying no risk factors of venous thromboembolism where tourniquet was used no longer than 60 minutes, pharmacological prophylaxis is not necessary. Only timely mobilisation is recommended. In patients displaying risk factors of venous thromboembolism or with tourniquet use surpassing 60 minutes, it is advisable to administer low molecular weight heparin in lower prophylactic dosage. In patients with lower extremity fractures treated with osteosynthesis, LMWH administration of 7-10 days is indicated. In patients with lower extremity injuries requiring plaster casting or other type of fixation reaching below the knee, LMWH administration is indicated over the whole period of fixation in persons with higher risk (people with venous thromboembolism in their histories, in direct relative's histories, people with thrombophilic conditions including poeple with malignancies, women using hormonal contraceptives or their substitutions). Aspirin is not a suitable drug for separate administration in the prophylaxis of venous thromboembolism in orthopaedic patients.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Femoral Fractures; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Risk Factors; Thromboembolism; Venous Thrombosis

Shortcomings of the existing anticoagulants, vitamin K antagonists and heparins, have led to the development of newer anticoagulant therapies. In particular, Vitamin K antagonists' slow onset of action, numerous drug interactions, narrow therapeutic window and need for frequent monitoring make it the most obvious target for replacement. Targeting specific coagulation enzymes or steps in the coagulation pathway, new anticoagulants have been or are under evaluation in clinical trials for a number of clinical indications, namely the prevention and treatment of venous thromboembolism, the prevention of ischemic stroke in patients with atrial fibrillation, and in acute coronary syndromes. Following a brief review of pharmacological aspects, this article will summarize the results of Phase III clinical trials evaluating the novel anticoagulants fondaparinux, ximelagatran and idraparinux. At present, most attention is directed at developing an oral anticoagulant to replace vitamin K antagonists for prevention of systemic thromboembolism. A number of newer agents are in both early and advanced stages of investigation.

Topics: Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Clinical Trials, Phase III as Topic; Fondaparinux; Humans; Oligosaccharides; Polysaccharides; Thromboembolism; Thrombosis; Venous Thrombosis

Prevention and treatment of the venous thromboembolic phenomena should be modified in a near future. The arrival of two new classes of anticoagulants: antifactor Xa and anti-factor IIa, opens a new perspective in an area in which low molecular weight heparins and oral anticoagulants have the exclusivity. Fondaparinux has the approval for its introduction into the market as a maximum representative of this group and has begun to be used. Among the direct antithrombotics we find melagatran and its oral form, ximelagatran, that opts to be the substitute of oral anticoagulants.

Topics: Antithrombin III; Antithrombins; Azetidines; Benzylamines; Fibrinolytic Agents; Fondaparinux; Forecasting; Humans; Polysaccharides; Venous Thrombosis

Venous thromboembolism (VTE) is a major problem in non-surgical patients admitted to the hospital, both during the hospitalization period and after discharge. Risk factors for VTE are well known and scoring systems have been published. Nevertheless, prophylaxis against VTE is in many hospitals used less often than ideal and also inappropriately. Electronic tools to alert the physicians to provide prophylaxis and suggest suitable measures have shown promising results with a reduction of clinically relevant VTE. Large randomized clinical trials have demonstrated efficacy of low molecular-weight heparin (LMWH), pentasaccharide(fondaparinux) and unfractionated heparin. The results were, however, driven by asymptomatic deep vein thrombosis (DVT), including distal DVT in some studies. A reduction of pulmonary embolism is achieved, but without any significant effect on the mortality. The agents are generally safe, with only a small increase of major bleeding, less with LMWH than with unfractionated heparin. The challenge is still to direct the efforts to the most appropriate patients.

Topics: Clinical Trials as Topic; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Premedication; Thromboembolism; Thrombosis; Treatment Outcome; 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

Patients with clinical conditions such as surgery, trauma, and acute medical illness have a transiently increased risk of venous thromboembolism and merit consideration for adequate thromboprophylaxis. The choice of an appropriate pharmacologic or physical means of prophylaxis should be made taking into account both the thrombotic and bleeding risk associated with patient-related factors and the type of surgery or other disease state involved. A large number of randomized clinical trials, meta-analyses, and guidelines developed by scientific societies worldwide have addressed this issue and have provided information and recommendations that should be considered carefully. The aim of this review is to provide the practicing physician with a brief updated summary of the subject, stratifying those patients at low thrombotic risk who do not require specific thromboprophylaxis apart from early ambulation, from those at moderate or higher thrombotic risk. Patients at moderate thrombotic risk face a 10 to 20% risk of deep vein thrombosis (DVT) and require prophylaxis with low-dose unfractionated heparin or low molecular weight heparins (LMWHs) at a dosage < 3400 U once daily, or with graduated elastic stockings if their bleeding risk is high. Patients with an expected 20 to 40% DVT rate without prophylaxis are considered at high thrombotic risk and should be treated preferentially with LMWHs at high prophylactic dosage (> 3400 U). Patients undergoing major orthopedic surgery face a DVT rate > 40%, are considered at very high risk of venous thromboembolism, and should be given either LMWHs at high prophylactic dosage, fondaparinux, or vitamin K antagonists--either alone or in association with intermittent pneumatic compression devices.

Topics: Anticoagulants; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Polysaccharides; Stockings, Compression; Thromboembolism; Venous Thrombosis

The antithrombin binding sequence of heparin, a pentasaccharide, has been synthesized as fondaparinux, an indirect, selective, and reversible factor Xa inhibitor. It can be administered subcutaneously, is well absorbed, and has a half-life of c. 17 hours permitting once-daily injection. It has been evaluated in an extensive study program in major orthopedic surgery, including hip fracture, and in major abdominal surgery with a large proportion of surgery for cancer. The effect is at least as effective as for low-molecular-weight heparins and it has also been shown effective for extended prophylaxis in hip fracture patients. Several thousands of patients have been studied and the substance is safe, although a slightly higher frequency of bleedings is found than in patients on low-molecular-weight heparins. There is no specific antidote but if necessary, recombinant activated factor VII can be used. Other side-effects are rare. Fondaparinux is cost saving and sometimes cost neutral when compared with enoxaparin.

Topics: Abdomen; Anticoagulants; Cost-Benefit Analysis; Drug Costs; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; Orthopedic Procedures; Polysaccharides; Surgical Procedures, Operative; Thromboembolism; Treatment Outcome; Venous Thrombosis

Extending the period of anticoagulation is an active area of investigation in both primary and secondary prevention of venous thromboembolic disease. In orthopaedic surgery, particularly in patients undergoing hip surgery, there is a growing interest in using extended anticoagulation beyond that traditionally given in the postoperative period using low-molecular weight heparin, oral anticoagulants, or newer agents such as fondaparinux sodium. Most studies show a benefit to extending anticoagulation without a considerable increase in major bleeding. There have been several large clinical trials addressing the question of extending oral anticoagulation in secondary prevention of venous thromboembolism (VTE). Just how long anticoagulation should be given in the treatment of venous thromboembolic disease remains an open question, depending on the nature of the initial VTE, associated patient risk factors and the risks of major bleeding. Future directions include the use of newer agents for anticoagulation as well as methods of better defining who will benefit most from extended anticoagulation based on an identification of risk factors with the aid of markers such as D-dimer or residual vein thrombosis.

Topics: Anticoagulants; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Postoperative Care; Secondary Prevention; Venous Thrombosis

The design and synthesis of new antithrombotic agents have led to numerous recent clinical trials to investigate their efficacy and safety. Analysis of the data from these trials, especially when the results were not totally expected, has provided interesting information, allowing a better understanding of the pathophysiology of thrombosis in various clinical situations. The aim of the present manuscript is to present the hypotheses on thrombogenesis generated by some of these recent clinical trials, notably those investigating the antithrombotic efficacy of a new synthetic and selective factor Xa inhibitor, fondaparinux. The antithrombotic efficacy of fondaparinux was recently investigated in a number of trials in the prevention and treatment of venous and arterial thrombotic disorders. In each case, the concept of the clinical efficacy of a selective factor Xa inhibitor has been proven. These trials have also clarified the implication and mode of action of factor Xa in these various types of thrombotic events. In the light of these trials, we discuss the clinical efficacy of such a selective factor Xa inhibitor, and other specific points such as the apparent lack of dose-dependency of its antithrombotic effect.

Topics: Anticoagulants; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; Polysaccharides; Postoperative Complications; Thrombin; Thromboembolism; Venous Thrombosis

Fondaparinux (Arixtra) is the first selective factor Xa inhibitor approved for use in thromboprophylaxis after orthopaedic surgery. New recently completed trials have also demonstrated the potential of fondaparinux in the prevention of venous thromboembolism (VTE) in other surgical and medical settings and in the treatment of established VTE. In the randomized double-blind PEGASUS study in high-risk abdominal surgery patients, fondaparinux reduced the incidence of VTE from 6.1% with dalteparin to 4.6% (odds ratio reduction = 25.8%, P = 0.14), without increasing the bleeding risk. In the randomized double-blind ARTEMIS trial in acutely ill medical patients, fondaparinux reduced the incidence of VTE from 10.5% with placebo to 5.6% (odds ratio reduction = 49.5%, P = 0.029), without increasing the bleeding risk; there was no pulmonary embolism in the fondaparinux group compared with five, all fatal, in the placebo group (P = 0.029). In the two MATISSE trials, both the efficacy and safety of once daily fondaparinux were at least as good as enoxaparin in the treatment of deep-vein thrombosis (MATISSE-DVT) and unfractionated heparin in the treatment of pulmonary embolism (MATISSE-PE). In patients with coronary artery disease, promising results were obtained in phase II trials and large phase III trials are ongoing. In conclusion, fondaparinux may further improve and simplify the prevention and treatment of thrombosis in a large range of medical and surgical settings.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombin III; Fondaparinux; Humans; Myocardial Infarction; Polysaccharides; Postoperative Complications; Thromboembolism; Venous Thrombosis

For patients with heparin-induced thrombocytopenia (HIT), reexposure to heparin is generally not recommended. However, these patients are likely to require anticoagulation therapy at some point in the future. During acute HIT, when thrombocytopenia and anti-heparin-platelet factor 4 antibodies (or HIT antibodies) are present, therapy with heparin must be avoided. In patients with subacute HIT, when platelets have recovered but HIT antibodies are still present, therapy with heparin should be avoided. In patients with a remote history of HIT, when HIT antibodies have cleared, heparin reexposure may be safe, although recurrent HIT has been described in some patients. For all of these patients, the use of alternate anticoagulant agents, including direct thrombin inhibitors and anti-Xa agents, is preferable. There is an increasing amount of data supporting the use of these alternative agents in a wide variety of clinical circumstances, including thromboprophylaxis and treatment of acute thrombosis. Except for a few clinical situations, it is generally possible to avoid heparin reexposure in patients with a history of HIT.

Topics: Angina, Unstable; Antibodies; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Female; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Male; Multiple Organ Failure; Platelet Factor 4; Polysaccharides; Pregnancy; Preoperative Care; Recombinant Proteins; Thrombin; Thrombocytopenia; Venous Thrombosis

Because the costs of anticoagulation therapy are substantial and the difference between the risks and benefits of this therapy are often narrow, economic analyses are particularly valuable when weighing anticoagulation options. Economic analyses to date suggest that anticoagulation is most effective and results in the greatest cost savings when applied to populations at highest risk for thrombotic events. They also suggest that in situations where a more costly anticoagulant agent is available, that agent is cost-effective only if it is clearly more efficacious or if it substantially reduces costs in other areas, such as hospitalization. These principles should guide clinicians' choices of anticoagulation strategies.

Topics: Anticoagulants; Cost-Benefit Analysis; Drug Costs; Fondaparinux; Health Care Costs; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Thromboembolism; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) is a common disease whose diagnosis is challenging. The best diagnostic approaches combine the patient's pretest clinical probability of disease with D-dimer testing and/or diagnostic imaging. In light of several advantages, low-molecular-weight heparins are now recommended over unfractionated heparin for most patients with acute VTE. Newer anticoagulants such as the factor Xa inhibitor fondaparinux also show promise for acute VTE. For chronic management, the duration and intensity of warfarin therapy should be tailored to the individual patient.

Topics: Anticoagulants; Antithrombins; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Probability; Risk Assessment; Risk Factors; Thromboembolism; Venous Thrombosis

Unfractionated heparin (UFH) may lead to symptomatic vertebral fractures in up to 3 out of every 100 people on long-term therapy. Ten-times that many people will experience a significant reduction in bone density leading to osteopoenia or osteoporosis. Low molecular weight heparins (LMWH) have been shown to be as effective as UFH in the prevention and treatment of venous thromboembolism. Several well-established advantages of LMWH over UFH include increased bioavailability, more predictable dose response, less intensive coagulation monitoring, and a lower probability of causing immune-mediated thrombocytopenia. There is also some evidence that long-term LMWH therapy is less likely to cause osteoporotic fractures and significant reductions in bone mass than UFH. Both UFH and LMWH undergo pharmacokinetic changes during pregnancy, which sometimes necessitates dosage adjustments. Fondaparinux is a synthetic antithrombotic agent, which specifically binds to antithrombin. It has been shown to be comparable to, or even more effective than, LMWH in the management of both arterial and venous thrombosis. Fondaparinux does not appear to have a negative effect on bone metabolism. Therefore, fondaparinux may be a safe and effective alternative to UFH and LMWH in women who require anticoagulation during pregnancy.

Topics: Adult; Anticoagulants; Bone Density; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Osteoporosis; Polysaccharides; Pregnancy; Pregnancy Complications; Risk Factors; Venous Thrombosis

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

Topics: Anticoagulants; Enoxaparin; Fondaparinux; Heparin; Humans; Meta-Analysis as Topic; Polysaccharides; Primary Prevention; Randomized Controlled Trials as Topic; Venous Thrombosis

Fondaparinux is the first synthetic selective Factor Xa inhibitor. Along with its antithrombotic efficacy, the safety of fondaparinux has been documented in several Phase II and III clinical trials, including the prevention of venous thromboembolism in patients undergoing major orthopaedic surgery or high-risk abdominal surgery, or in acutely ill medical patients with restricted mobility, and the treatment of patients with deep-vein thrombosis and pulmonary embolism. In all these indications, the safety of fondaparinux used according to its registered regimen was similar to that of reference comparators. In conclusion, due to its superior efficacy and satisfactory safety, fondaparinux may substantially improve the prevention and treatment of venous thrombosis.

Topics: Anticoagulants; Clinical Trials as Topic; Fondaparinux; Hemorrhage; Humans; Polysaccharides; Risk Factors; Thromboembolism; Venous Thrombosis

Heparin has been the mainstay of treatment and prevention of venous and arterial thromboembolism for many years. Its use, however, is associated with a serious and potentially fatal immunological drug reaction termed heparin-induced thrombocytopenia (HIT). Current treatment consists of discontinuing heparin therapy and the administration of an alternate anticoagulant (e.g. danaparoid, lepirudin, bivalirudin or argatroban). Fondaparinux is a novel synthetic heparin pentasaccharide capable of inhibiting factor Xa via the action of antithrombin (AT) but devoid of anti-factor IIa (thrombin) activity. Although the drug is identical in structure to the pentasaccharide domain found on unfractionated heparin (UH), it is too small to be recognized by the majority of heparin-reactive antibodies. It is theoretically an excellent candidate agent for the treatment of HIT. Currently, fondaparinux is licensed for orthopaedic venous thromboprophylaxis but not for the treatment of HIT. Successes in the use of fondaparinux in the treatment of HIT, as demonstrated in recent published case reports, warrant further study in larger controlled trials for this indication.

Topics: Anticoagulants; Female; Fondaparinux; Heparin; Humans; Male; Polysaccharides; Thrombocytopenia; Thromboembolism; Venous Thrombosis

Venous thromboembolism (VTE) remains a significant cause of morbidity and mortality in hospitalized patients with acute medical illness. The high prevalence of VTE in this patient population, its clinically silent nature, and associated morbidity and mortality indicate that prophylactic therapy is appropriate in those determined to be at increased risk. Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) have been shown to reduce the incidence of VTE and are the primary therapies used for prophylaxis in these patients. Although both UFH and LMWH have received grade 1A recommendations for the prevention of VTE in at-risk medical patients in the 2004 American College of Chest Physicians consensus conference statements, LMWH has advantages over UFH in its once-daily dosing scheme, reduced incidence of major and minor bleeding events, and reduced incidence of heparin-induced thrombocytopenia. Fondaparinux is a novel antithrombotic agent characterized by specificity for factor Xa and a lack of platelet interaction. A recent clinical trial in hospitalized patients with acute medical illness found that fondaparinux significantly reduced the incidence of both VTE and fatal pulmonary embolism compared with placebo, without increased major bleeding. Despite the availability of effective thromboprophylactic therapies, VTE prophylaxis continues to be underutilized in hospitalized medical patients.

Topics: Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Polysaccharides; Risk Factors; Thromboembolism; Venous Thrombosis

Patients undergoing major lower-extremity orthopedic surgery such as total hip replacement (THR) and total knee replacement (TKR) are at an increased risk of venous thromboembolism (VTE). Routine prophylaxis is necessary to reduce the risk of deep vein thrombosis (DVT), which may progress to potentially fatal pulmonary embolism and secondary complications such as postthrombotic syndrome, recurrent DVT, and chronic pulmonary hypertension. Prophylaxis in patients undergoing TKR, THR, and hip fracture surgery is now standard practice and generally involves anticoagulant treatment with either low-molecular-weight heparin (LMWH) or warfarin for a period of 7 to 10 days, with extended prophylaxis in those with ongoing risk factors such as obesity, cancer, or previous VTE. Data from clinical practice suggest that there is a general trend toward longer postsurgical prophylaxis and shorter hospital stays, making practicality of treatment an important consideration. LMWH is effective for the prophylaxis of VTE, but the parenteral route of administration is not convenient for use in the outpatient setting. Warfarin, on the other hand, can be administered orally but requires the infrastructure for careful patient monitoring and dose adjustments because of its unpredictable dose-response relationship. The development of new anticoagulants has been pursued with the aim of improving efficacy, predictability, consistency of response, safety, and convenience. A recently approved anticoagulant, fondaparinux, has been proven to provide superior efficacy for the prevention of VTE compared with LMWH, but this agent requires parenteral administration and does not overcome the convenience issue. Ximelagatran is the oral form of the direct thrombin inhibitor melagatran, which is available for subcutaneous administration. Ximelagatran has a consistent anticoagulant response allowing fixed oral dosing without the need for coagulation monitoring. The efficacy and safety profile of melagatran/ximelagatran prophylaxis for VTE following THR and TKR has compared favorably with standard LMWH prophylaxis, as seen in the European METHRO II and III trials and EXPRESS trial, and with warfarin prophylaxis, as seen in the North American EXULT A and B trials. Several prophylactic treatment regimens have been evaluated in the European trials to determine the optimal dosing and timing of first dose of melagatran to achieve the best balance of efficacy and safety. Preoperative initiation of melag

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Azetidines; Benzylamines; Clinical Trials as Topic; Fondaparinux; Humans; Polysaccharides; Treatment Outcome; Venous Thrombosis

Anticoagulant therapy plays an important role in the prevention and treatment of pathologic arterial and venous thrombosis. There is increasing enthusiasm in the inhibition of Factor Xa as a target to achieve therapeutic anticoagulation because of its central and 'upstream' position in the coagulation process. The indirect, selective, parenteral Factor Xa inhibitor fondaparinux sodium (synthetic pentasaccharide) has been studied extensively in the prevention and treatment of venous thromboembolism. In an overview of four studies in patients undergoing major orthopedic surgery, fondaparinux sodium was associated with a 55% reduction in recurrent thromboembolism, albeit with a modest increase in bleeding. Preliminary results from phase II studies of fondaparinux sodium in patients with ST-elevation and non-ST-elevation acute coronary syndromes have been promising and have led to the initiation of two large phase III trials, which are currently underway. Idraparinux sodium, a long-acting synthetic pentasaccharide, is currently being investigated as a once-weekly alternative to other long-term anticoagulants. DX-9065a and razaxaban are two of many direct selective Factor Xa inhibitors currently in development. DX-9065a has been studied in phase II trials in patients undergoing percutaneous coronary intervention and in those with non-ST-elevation acute coronary syndromes. Razaxaban has been studied in a phase II trial in patients who have undergone orthopedic surgery. Data from these trials, although preliminary and based on small numbers of patients, suggest that direct selective Factor Xa inhibition may provide effective anticoagulation, perhaps without excessive bleeding. Inhibition of Factor Xa is a promising target for the prevention and treatment of thrombosis in both the venous and arterial circulation. Ongoing investigation with numerous oral and parenteral inhibitors of Factor Xa will establish the potential of Factor Xa as a target for therapeutic anticoagulation.

Topics: Amino Acid Sequence; Angioplasty, Balloon, Coronary; Animals; Anticoagulants; Antithrombin III; Blood Coagulation; Drug Design; Fondaparinux; Humans; Molecular Sequence Data; Naphthalenes; Polysaccharides; Propionates; Venous Thrombosis

Unfractionated heparin, derived from porcine intestine, is the prototype of a rapidly acting anticoagulant. It has been used for over 60 years to arrest or prevent thrombus growth. Low-molecular-weight heparins, available in the last 20 years, are manufactured from unfractionated heparin and have superior dose-response relationships because of fewer nonspecific reactions with plasma proteins and cells. Fondaparinux is a recently approved five-saccharide synthetic molecule that carries the evolution of heparin further. It is a pure Xa inhibitor, with minimal nonspecific interactions. It does not appear to elicit the antibody that leads to heparin-induced thrombocytopenia (HIT). All of these agents are given either intravenously or subcutaneously. They act indirectly by activating the natural plasma inhibitor, antithrombin III. Direct thrombin inhibitors bind directly to thrombin's active site without interaction with the cofactor, antithrombin III. Lepirudin (Refludan; Berlex, Wayne, NJ) and argatroban (Argatroban; GlaxoSmithKline, Research Triangle Park, NC) are given intravenously and are usually used in HIT and thrombosis associated with HIT. Bivalirudin (Angiomax; The Medicines Company, Parsippany, NJ) is a parenteral direct thrombin used in place of heparin in percutaneous coronary interventions. Ximelagatran (Exanta; AstraZeneca, Wilmington, DE) is an oral direct thrombin inhibitor under development for both acute and chronic anticoagulation.

Topics: Anticoagulants; Arginine; Azetidines; Benzylamines; Embolism; Enzyme Inhibitors; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia; Venous Thrombosis

In this paper, recent advances in new anticoagulants with the potential to be used for prevention or treatment of venous thrombosis are reviewed.. Numerous novel anticoagulants targeting specific stages of the coagulant pathway are in various stages of development. Fondaparinux, an indirect activated factor VII inhibitor, has been shown to be effective for initial treatment and prevention of venous thromboembolism, but still requires parenteral administration. Ximelagatran, an oral direct thrombin inhibitor, has also been shown to effective for treatment and prevention of venous thrombosis. Both agents are associated with bleeding, however, and ximelagatran is associated with hepatic toxicity with long-term use. Direct activated factor X inhibitors, orally available forms of heparin, and other direct thrombin inhibitors remain in early stages of development. Further data on the clinical utility of these agents are likely to emerge in the next few years, and uptake of their use will be affected by the cost considerations.. Numerous alternative anticoagulants are in varying stages of development. Clinical data have yet to show that these agents have a clearly superior risk-benefit ratio compared with currently used antithrombotics. Many drugs remain in initial stages of development. The ideal anticoagulant agent is being sought but has yet to be discovered.

Topics: Anticoagulants; Azetidines; Benzylamines; Factor VIIa; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombin; Thrombocytopenia; Venous Thrombosis

Modern approaches to prevention of venous thromboembolic complications in patients with chronic heart failure are analyzed in this review which contains results of large studies of low molecular weight heparins. In MEDENOX trial the use of enoxaparin in medical patients was associated with 63% reduction of risk of thrombosis. The authors own experience showed that 2 weeks of therapy with enoxaparin in patients with chronic stage IIB-III heart failure caused significant lowering of soluble fibrin-monomer complexes, fibrinogen, and index of turbo-dynamic potential. These changes evidenced for decreased intravascular blood coagulation. Thus enoxaparin can be effectively used for prevention of thrombosis and thromboembolism in patients with chronic heart failure. Novel antithrombotic agents fondaparinux, idraparinux, ximelagatran, recombinant thrombomodulin are perspective medications for prevention of venous thromboses and embolism in medical patients.

Topics: Anticoagulants; Azetidines; Benzylamines; Dalteparin; Double-Blind Method; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Heart Failure; Humans; Multicenter Studies as Topic; Oligosaccharides; Placebos; Polysaccharides; Randomized Controlled Trials as Topic; Risk Factors; Thromboembolism; Thrombomodulin; Thrombosis; Time Factors; 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

Anticoagulant therapy is effective at preventing the development of venous thromboembolism in high-risk patients, and reduces morbidity and mortality in individuals with established thromboembolic disease. Vitamin K antagonists and heparins are currently the most commonly used anticoagulant drugs, but they have practical limitations. Therefore, new antithrombotic agents with predictable dose-responses (thereby decreasing the need for monitoring without compromising efficacy or safety), ideally available in an oral formulation and with a rapidly reversible anticoagulant effect, are needed. New drugs fulfilling some of the above criteria have been developed and have proven to be effective agents for the treatment and prevention of venous thromboembolism.

Topics: Animals; Anticoagulants; Azetidines; Benzylamines; Blood Coagulation; Factor VII; Factor Xa Inhibitors; Fondaparinux; Helminth Proteins; Humans; Oligosaccharides; Polysaccharides; Recombinant Proteins; Thrombin; Thromboembolism; Thrombomodulin; Thromboplastin; Treatment Outcome; Venous Thrombosis

Anticoagulation is highly effective in the prevention and treatment of venous thromboembolism (VTE). Since decades, vitamin K antagonists (VKA) were the only available oral anticoagulants. Even though VKA are very effective, they have numerous practical problems: Due to their narrow therapeutic window, highly variable dose requirements and drug interactions, close monitoring is mandatory, aiming towards an INR of 2-3 for most indications. At present, new oral anticoagulants are being studied, such as the oral direct thrombin inhibitor Ximelagatran, which in trials for prevention and treatment of VTE appears at least equivalent to heparin and VKA. Heparins have to be administered parenterally, and low molecular-weight heparins have been able to overcome some of the shortcomings of standard heparins, such as limited bioavailability, variable dose response and heparin induced thrombocytopenia (HIT). Heparinoids and hirudins are alternative anticoagulants to treat HIT. With the development of synthetic pentasaccharides, such as Fondaparinux an increase in efficacy could be achieved in high-risk thromboprophylaxis.

Topics: Anticoagulants; Azetidines; Benzylamines; Dose-Response Relationship, Drug; Drug Therapy; Evidence-Based Medicine; Fondaparinux; Heparin; Humans; Patient Care Management; Polysaccharides; Practice Patterns, Physicians'; Thrombocytopenia; Treatment Outcome; Venous Thrombosis; Vitamin K

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

Fondaparinux (Arixtra) is the first of a new class of antithrombotic compounds - Factor Xa inhibitors. This synthetic pentasaccharide acts by inhibiting Factor Xa selectively. Its efficacy and safety have been demonstrated in animal models of venous and arterial thromboses and bleeding risk. In humans, its pharmacokinetic profile after subcutaneous injection shows a rapid onset of antithrombotic activity and an elimination half-life that reliably allows once-daily dosing. As the inter-subject variability is limited, no laboratory monitoring of coagulation parameters is needed. The efficacy and safety of fondaparinux have been examined in several Phase II and III clinical trials. So far, the largest programme has involved approximately 9000 patients undergoing major orthopaedic surgery of the lower limbs. In the setting of short-term prophylaxis, the efficacy of fondaparinux for preventing venous thromboembolism was significantly superior to that of the low-molecular-weight heparin, enoxaparin (common reduction in risk: 50.6%; p < 0.001). The benefit of extended thromboprophylaxis with fondaparinux in hip fracture surgery patients was also demonstrated. Fondaparinux also showed benefit in the prevention of venous thromboembolism in other surgical and medical settings and in the treatment of patients with venous thromboembolism. Overall, fondaparinux therapy was as well-tolerated as currently available treatments. In conclusion, selective inhibition of Factor Xa is an effective antithrombotic strategy. Fondaparinux may substantially improve the prevention and treatment of thrombosis. Fondaparinux 2.5 mg once-daily s.c. has been approved for the prevention of venous thromboembolism after major orthopaedic surgery. Fondaparinux use in extended prophylaxis (4 weeks) after hip fracture surgery has also been recently approved.

Topics: Clinical Trials as Topic; Drug Interactions; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Thromboembolism; Venous Thrombosis

Fondaparinux (Arixtra) is the first synthetic selective Factor Xa inhibitor. Its efficacy and safety in the prevention of venous thromboembolism (VTE) was first studied in patients undergoing major orthopedic surgery, a setting in the highest risk category for postoperative thrombotic complications. Low-molecular-weight heparins are frequently used in this setting, but the rates of VTE still range between 15% and 33%. In large clinical trials, fondaparinux started 6 hours postoperatively was significantly more effective than enoxaparin in preventing VTE in patients undergoing total hip replacement, total knee replacement or hip fracture surgery. The benefit of extended fondaparinux prophylaxis after hip fracture surgery was also investigated. Other trials have demonstrated that fondaparinux is efficacious in the prevention of VTE in other patient populations at risk of thrombosis and in the treatment of symptomatic VTE.

Topics: Factor Xa Inhibitors; Fondaparinux; Humans; Myocardial Ischemia; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Treatment Outcome; Venous Thrombosis

Topics: Anticoagulants; Azetidines; Benzylamines; Clinical Trials, Phase III as Topic; Drug Design; Factor Xa Inhibitors; Follow-Up Studies; Fondaparinux; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Recurrence; Thromboembolism; Thrombophilia; Venous Thrombosis; Vitamin K

The fondaparinux trials in venous thromboembolism (VTE) prevention after orthopaedic surgery have been subject to methodological criticisms recently summarised in this journal. These criticisms merit comments and corrections. Fondaparinux reduced the risk of VTE and of proximal deep-vein thrombosis by more than 55% compared with enoxaparin, based on the efficacy endpoint that supported the registration and use of low-molecular-weight heparins (LMWH) in all their prophylactic indications, an endpoint endorsed by international consensus statements and health authorities. Fondaparinux is the only antithrombotic agent that significantly reduced the rate of symptomatic VTE in a single orthopaedic surgery trial that was powered to detect this effect. In contrast to the paucity of data available on LMWH, the relationship between the timing of first administration and efficacy and safety has been well documented for fondaparinux. Fondaparinux used according to its approved regimen provides a simple, easy-to-use, effective and safe post-operative regimen for all orthopaedic surgery patients.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Enoxaparin; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Postoperative Care; Preoperative Care; Randomized Controlled Trials as Topic; Thromboembolism; Treatment Outcome; Venous Thrombosis

Fondaparinux sodium (Arixtra; fondaparinux) is the first of a new class of synthetic pentasaccharide anticoagulants that bind to antithrombin and inhibit the action of factor Xa. In three large, well designed trials, subcutaneous fondaparinux 2.5mg once daily was more effective than subcutaneous enoxaparin sodium (enoxaparin) 30 mg twice daily or 40 mg once daily at preventing venous thromboembolism (VTE) at day 11 in patients undergoing hip replacement, elective major knee or hip fracture surgery; a fourth trial demonstrated similar efficacy to enoxaparin 30 mg twice daily in hip replacement. Fondaparinux recipients had a lower incidence of proximal deep vein thrombosis (DVT) in two studies. In a meta-analysis of the four trials, patients receiving fondaparinux had a >50% reduction in the relative risk of VTE at day 11. Fondaparinux compared favourably with enoxaparin in several pharmacoeconomic analyses. In a large, controlled trial in hip fracture patients, extended prophylaxis with fondaparinux (duration 25-31 days) substantially reduced the incidence of VTE at day 25-32 compared with prophylaxis for 6-8 days, and was a cost-effective treatment strategy. Moreover, extended prophylaxis significantly decreased the rate of proximal, total and distal DVT and symptomatic VTE. Fondaparinux was generally well tolerated in clinical trials in patients undergoing major orthopaedic surgery. However, following major knee surgery and in a meta-analysis of pooled data from four trials, fondaparinux recipients had a significantly higher incidence of overt bleeding with a bleeding index > or =2, but no increase in fatal bleeding, bleeding into a critical organ or bleeding leading to reoperation. The bleeding risk is related to the timing of the first dose and when fondaparinux was initiated between 6 and 8 hours after surgery, the bleeding risk was similar to enoxaparin. Extended prophylaxis with fondaparinux was not associated with a significantly increased risk of bleeding events. In conclusion, fondaparinux is more effective than enoxaparin at preventing postoperative VTE in patients undergoing elective hip replacement, major knee or hip fracture surgery. Extended therapy with fondaparinux considerably increases its efficacy without a significant increase in the incidence of bleeding episodes. Fondaparinux was generally well tolerated in clinical trials. Fondaparinux is an effective and useful alternative to low molecular weight heparins for the prevention of VTE

Topics: Clinical Trials as Topic; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Venous Thrombosis

Topics: Anticoagulants; Arginine; Azetidines; Benzylamines; Fondaparinux; Glycine; Heparin; Hirudin Therapy; Humans; Pipecolic Acids; Polysaccharides; Prodrugs; Sulfonamides; Thrombin; Venous Thrombosis

Aging itself is a risk factor for venous thromboembolism, and the prevalence in the elderly of additional risk factors (e.g. cancer, orthopedic surgery, immobility) increase its intrinsic risk. Many in the medical community are reluctant to prescribe anticoagulation (for primary and secondary prevention of venous thromboembolism) to their geriatric patients for the fear that bleeding complications may outweigh the benefits. A thorough analysis of the data support the concept that the under-use of heparin in primary prevention in the elderly is more related to medical beliefs than to facts. The risk of bleeding due to oral anticoagulants (secondary prevention) is greatly reduced by keeping the International Normalized Ratio (INR) values within therapeutic ranges and carefully avoiding conditions/drugs that may interfere with such treatment. The oral direct thrombin inhibitor ximelagatran has been studied for primary (hip and knee replacement surgery) and for secondary prophylaxis of venous thromboembolism, and for acute venous thromboembolism treatment. The selective factor Xa inhibitor fondaparinux has been approved for primary prophylaxis of venous thromboembolism in hip and knee replacement surgery and in hip fracture surgery. Studies on the latter drugs, where most of the patients were > 65 years of age, further show that the fear of bleeding complications due to anticoagulation in the elderly is largely unjustified.

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Anticoagulants; Azetidines; Benzylamines; Clinical Trials as Topic; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Humans; International Normalized Ratio; Polysaccharides; Risk Factors; Thromboembolism; Time Factors; Venous Thrombosis

The aim of this review is to perform a critical analysis of all completed studies evaluating pentasaccharides-synthetically derived, selective inhibitors of activated factor X-in prophylaxis in major orthopedic surgery and the treatment of venous thromboembolism.. Venous thromboembolism is a disorder with considerable morbidity when left untreated. New antithrombotic agents have been developed that selectively inhibit components of the coagulation system, thereby avoiding the difficulties associated with current anticoagulants. The pentasaccharides fondaparinux and idraparinux are the first of a new class of synthetic selective inhibitors of activated factor X. Fondaparinux has been extensively investigated in two areas: orthopedic surgery and venous thromboembolism. It is clear from four thromboprophylaxis studies in major orthopedic surgery that fondaparinux is 50% more effective in reducing venous thromboembolism than enoxaparin. This superior efficacy led to an overall increase in major bleeding, which was however primarily due to more fondaparinux-treated patients with bleeding indexes of 2 or greater. The incidence of fatal bleeding, critical organ bleeding, or bleeding leading to reoperation did not differ significantly between the two groups. In the initial treatment of patients with proximal vein thrombosis and pulmonary embolism, fondaparinux was equally effective as low molecular weight heparins and unfractionated heparin, respectively, without a different incidence in major bleeding in fondaparinux and comparator heparin groups.. Fondaparinux, one of the first of a new class of synthetic selective factor Xa inhibitors, is overall 50% more effective in reducing venous thromboembolism than enoxaparin in major orthopedic surgery, with an overall 1% increased rate of major bleeding, when compared with enoxaparin. The incidence of fatal bleeding, critical organ bleeding, or bleeding leading to reoperation did not differ significantly between the two treatment groups. Fondaparinux is equally effective as low molecular weight heparins and unfractionated heparin in the initial treatment of patients with proximal vein thrombosis and pulmonary embolism, respectively. Finally, as with any new drug, fondaparinux should be used cautiously and only in patients who reflect the population of the clinical trials in which the drug was evaluated.

Topics: Clinical Trials as Topic; Factor Xa Inhibitors; Fondaparinux; Humans; Oligosaccharides; Orthopedic Procedures; Polysaccharides; Thromboembolism; Venous Thrombosis

Venous thromboembolism is a multifactorial silent disease and tends not to be suspected by physicians, especially in medical patients. Pulmonary embolism is the most preventable cause of death among hospitalized patients. It is of major importance to assess the risk for venous thromboembolism and to adapt the prophylactic strategy with the aim of improving the risk-benefit ratio of the prophylaxis.. Prophylaxis of venous thromboembolism can be done by either mechanical means or pharmacologic agents or both. The Medenox trial, the Prime study, the Prince study, the Prevent study, and the Artemis trial demonstrated that acutely ill medical patients are at increased risk of venous thromboembolism and that low molecular weight heparins (enoxaparin 40 mg or dalteparin 5000 IU subcutaneously once daily for 10 days) as well as fondaparinux 2,5 mg subcutaneously once daily for 10 days have a favorable risk-benefit ratio in the prevention of venous thromboembolism in acutely ill medical patients. The publication of the results of the Exclaim study is expected to clarify the optimal duration of prophylaxis in this group of patients. Patients hospitalized in medical intensive care units as well as patients with active cancer or central venous catheters are at increased risk of venous thromboembolism, and the studies published so far demonstrate the favorable risk-benefit ratio of thromboprophylaxis with either low molecular weight heparins or low-dose warfarin.. Acutely ill medical patients are at increased risk of venous thromboembolism. Prophylaxis with low molecular weight heparins and fondaparinux is effective and safe. Initiatives to improve venous thromboembolism prophylaxis should be based on the education of physicians regarding the individualized risk assessment.

Topics: Anticoagulants; Dalteparin; Enoxaparin; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Humans; Polysaccharides; Risk Factors; Thromboembolism; Venous Thrombosis; Warfarin

Patients undergoing orthopedic surgery represent one of the highest risk groups for the development of venous thromboembolism (VTE). Evidence shows that this risk extends beyond the period in which the patient is hospitalized, especially for patients undergoing hip surgery. Clinical trials have shown that extended prophylaxis with the low-molecular-weight heparins is effective in reducing the rate of total VTE, and a meta-analysis demonstrated a reduction in symptomatic VTE with extended prophylaxis after total hip replacement surgery. Based on these results, the American College of Chest Physicians gives a grade 2A recommendation for the use of extended prophylaxis after orthopedic surgery. Until recently, data evaluating the role of prophylaxis in patients undergoing hip fracture surgery were limited. Subsequently, a novel anticoagulant, fondaparinux, demonstrated significant benefit in these patients and has become the first and only agent approved by the United States Food and Drug Administration (FDA) for use in patients undergoing hip fracture surgery Despite the limitations of the older trials, their findings supported the need to evaluate extended prophylaxis in patients undergoing hip fracture surgery. In the first well-conducted trial of extended prophylaxis for hip fracture surgery, fondaparinux provided impressive results in reducing total and symptomatic VTE. The results of this trial have once again led to fondaparinux being the first and only agent to be granted FDA approval for the indication of extended prophylaxis in patients undergoing hip fracture surgery.

Topics: Anticoagulants; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Thromboembolism; Venous Thrombosis

In four randomized, controlled studies of patients undergoing orthopedic surgery, the antithrombotic efficacy and safety of subcutaneous fondaparinux 2.5 mg once/day were compared with those of subcutaneous enoxaparin regimens that were approved by the United States Food and Drug Administration. In patients undergoing elective hip replacement surgery, fondaparinux significantly reduced the frequency of venous thromboembolism (VTE). However, in a second trial that compared fondaparinux with enoxaparin 30 mg twice/day beginning 12-24 hours after surgery, a 26% risk reduction in favor of fondaparinux was not statistically significant. In patients undergoing elective knee replacement surgery, fondaparinux significantly reduced the risk of VTE compared with enoxaparin without increasing the risk of clinically relevant bleeding, although the risk of major bleeding defined by the bleeding index was significantly higher with fondaparinux. Fondaparinux was superior to enoxaparin 40 mg once/day in the setting of hip fracture surgery, with no increased risk of major bleeding. Meta-analysis of the four studies confirms the superior antithrombotic efficacy of fondaparinux over enoxaparin in orthopedic surgery and suggests that the risk of major bleeding is similar to that of enoxaparin when the first dose of fondaparinux is given at least 6 hours after surgery.

Topics: Anticoagulants; Enoxaparin; Fondaparinux; Humans; Meta-Analysis as Topic; Orthopedic Procedures; Polysaccharides; Randomized Controlled Trials as Topic; Thromboembolism; 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) is the cause of significant morbidity and mortality and may lead to other complications, including recurrent VTE and long-term postthrombotic syndrome. Venous thromboembolism represents a huge health economic burden of nearly 500 million dollars/year in the United States. Without adequate prophylaxis, patients undergoing major orthopedic surgery are at high risk of developing VTE. Prophylaxis with either unfractionated heparin or warfarin not only substantially reduces the risk of VTE after orthopedic surgery, but also is more cost-effective than no prophylaxis. Low-molecular-weight heparins (LMWHs) have been shown to be superior to unfractionated heparin or warfarin, and despite the fact that they are more expensive, they are cost-effective. Large-scale clinical trials have shown that fondaparinux further reduces the likelihood of VTE complications after major orthopedic surgery. A review of the pharmacoeconomic evaluations of fondaparinux leads to the conclusion that fondaparinux is a cost-effective alternative to LMWHs in VTE prophylaxis.

Topics: Cost-Benefit Analysis; Fibrinolytic Agents; Fondaparinux; Heparin; Humans; Orthopedic Procedures; Polysaccharides; Randomized Controlled Trials as Topic; Thromboembolism; Venous Thrombosis

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 results of studies of the comparative efficacy, safety, feasibility, and costs of using low molecular weight heparin (LMWH) or unfractionated heparin (UFH) for the treatment of venous thromboembolism (VTE) are reviewed. Cost-effectiveness research comparing LMWH with warfarin or UFH and comparing the activated factor X inhibitor fondaparinux with LMWH for VTE prophylaxis also is discussed.. The greater ease of administration, fewer laboratory monitoring requirements, and feasibility of using LMWH safely on an outpatient basis instead of on an inpatient basis facilitate earlier hospital discharge and make LMWH more cost-effective than UFH for the treatment of DVT. The use of LMWH instead of warfarin to prevent VTE increases costs, but it is more effective for preventing DVT and death at a relatively small incremental cost per DVT event avoided and cost per death averted. The total expected costs are higher, but the expected cost per DVT event avoided is lower when enoxaparin is used instead of UFH for VTE prophylaxis.. Fondaparinux is more cost-effective than enoxaparin for VTE prophylaxis, with a cost saving that increases progressively over time.

Topics: Clinical Trials as Topic; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Thromboembolism; Venous Thrombosis

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

Fondaparinux (Arixtra, GlaxoSmithKline, Philadelphia, PA.) is the first synthetic selective factor Xa inhibitor. A worldwide phase III program, that consists of four randomized, double-blind trials, in patients who underwent surgery for hip fracture, and elective hip replacement and elective major knee surgery was conducted to compare the benefit-to-risk ratio of a subcutaneous 2.5 mg once-daily regimen of fondaparinux starting postoperatively versus enoxaparin in preventing venous thromboembolism. The overall incidence of venous thromboembolism up to day 11 was reduced from 13.7% in the enoxaparin group, to 6.8% in the fondaparinux group, with a relative risk reduction of 50.6% in favor of fondaparinux (95% confidence interval: 40.9% to 59.1%, p<0.001). The overall incidence of clinically relevant bleeding was low and did not differ between the two groups. The benefit of fondaparinux was consistent across all types of surgery and all subgroups. The further randomized, double-blind PENTHIFRA-PLUS trial showed that extending fondaparinux prophylaxis from one to four weeks after hip fracture surgery was well tolerated and, compared to one-week fondaparinux, dramatically reduced delayed venous thromboembolism events from 35.0% to 1.4% (p<0.001). Four-week fondaparinux could become the standard thromboprophylaxis after hip fracture surgery. Fondaparinux is the first selective factor Xa inhibitor approved for use in thromboprophylaxis after orthopedic surgery.

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Clinical Trials, Phase III as Topic; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Enoxaparin; Female; Follow-Up Studies; Fondaparinux; Humans; Incidence; Injections, Subcutaneous; Male; Odds Ratio; Polysaccharides; Postoperative Complications; Randomized Controlled Trials as Topic; Risk Assessment; Thromboembolism; Treatment Outcome; Venous Thrombosis

Factor X plays a central role in coagulation, being the point of convergence of the extrinsic and intrinsic pathways of blood clotting. It may also act as one of the links between the coagulation and inflammatory pathways. These findings suggest that factor X may represent an attractive target for a new antithrombotic drug. Indeed, a factor X inhibitor, fondaparinux, has already been approved for clinical use to prevent post-operative deep vein thrombosis. Factor X inhibitors are also being evaluated for use in the treatment of the acute coronary syndromes, pulmonary embolism and deep vein thrombosis. Oral factor X inhibitors are also being developed, which may be of use in the outpatient prevention and/or treatment of stroke and thromboembolism.

Topics: Anticoagulants; Clinical Trials as Topic; Factor X; Factor Xa Inhibitors; Fondaparinux; Humans; Polysaccharides; Postoperative Complications; Stroke; Thromboembolism; Venous Thrombosis

The aim of thromboprophylaxis is to minimise the incidence of clinically relevant venous thromboembolism (VTE) but in many trials designed to determine the efficacy of thromboprophylactic agents, asymptomatic VTE is included in the primary endpoint. Since asymptomatic events occur much more frequently than symptomatic events, they dominate the results. Data from trials comparing the thromboprophylactic efficacy of enoxaparin and fondaparinux in orthopaedic surgical patients are used to demonstrate that asymptomatic and symptomatic endpoints may yield different conclusions. There was no difference between these agents in the incidence of symptomatic VTE. Efficacy and safety results of thromboprophylactic studies are affected by other aspects of trial design such as the dose of each agent and the timing of treatment initiation and endpoint assessment. Such factors should be considered when designing clinical trials and evaluating their results.

Topics: Anticoagulants; Clinical Trials as Topic; Double-Blind Method; Enoxaparin; Fondaparinux; Humans; Polysaccharides; Postoperative Complications; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome; Venous Thrombosis

Fondaparinux (Arixtra, Sanofi-Synthelabo, Paris, France) is a pentasaccharide that selectively inhibits factor Xa; it is the first of a new class of synthetic antithrombotic agents. Fondaparinux has a linear pharmacokinetic profile allowing once-daily subcutaneous administration. Absence of metabolism, complete bioavailability, and lack of nonspecific binding in plasma contribute to the predictability of its effect. Fondaparinux has been approved for use in the prophylaxis of venous thromboembolism following orthopedic surgery. In this setting, it was found to reduce VTE risk by more than 50% in comparison with the low molecular weight heparin enoxaparin, with an incidence of clinically important bleeding not significantly different from that of standard low molecular weight heparin regimens. Furthermore, 4 weeks of prophylaxis with fondaparinux after hip fracture surgery was shown to reduce the risk of venous thromboembolism by 96% compared with 1-week prophylaxis. Finally, the efficacy and safety of fondaparinux in the treatment of venous thromboembolism and acute coronary syndromes appears promising.

Topics: Acute Disease; Antithrombin III; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Coronary Disease; Double-Blind Method; Female; Fondaparinux; Humans; Injections, Subcutaneous; Male; Meta-Analysis as Topic; Orthopedic Procedures; Polysaccharides; Pregnancy; Pregnancy Complications, Cardiovascular; Randomized Controlled Trials as Topic; Thromboembolism; Treatment Outcome; Venous Thrombosis

Inhibition of activated coagulation factor X (FXa) is an attractive target for antithrombotic treatment strategies, because of the central position of FXa in the coagulation cascade. Most of the now available anticoagulant drugs have inhibitory effects not only on FXa, but also on thrombin. With the development of pentasaccharides, a new class of antithrombotic agents has emerged that acts by specific inhibition of FXa and lacks activity against FIIa. Fondaparinux, the first synthetic short-acting pentasaccharide, has been evaluated, in a large phase II and III clinical programme concerning prophylaxis and treatment of venous thromboembolism and also in phase II studies in patients with acute coronary syndromes. Idraparinux, the long-acting pentasaccharide, has been studied in a dose-finding study in patients with established deep-vein thrombosis and phase III studies are now planned in patients with venous thromboembolism and in patients with atrial fibrillation.

Topics: Acute Disease; Anticoagulants; Blood Coagulation; Coronary Disease; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Oligosaccharides; Polysaccharides; Thromboembolism; Thrombosis; Venous Thrombosis

Two new classes of anticoagulants are actually developed which would change in the near future our strategies for the prevention and the treatment of venous thromboembolic events. These two classes are the anti-factor Xa and anti-factor IIa (direct antithrombin) agents. Among the anti factor Xa, the pentasaccharides are initiating their clinical use. Fondaparinux is a synthetic form of the natural pentasaccharide, its pharmacokinetics allows one s.c. administration/24 hours. It is active in prevention and treatment of venous thromboembolic and coronary thrombotic events. A modified form (idraparinux) whose pharmacokinetics allows one administration only once a week should have the same type of efficacy. Among direct antithrombin agents, hirudin and derivatives have been developed in the past decade with a limited use due to several drawback. More recently synthetic direct antithrombins modified to allow oral route have been developed, the most advanced in development, melagatran, is active in the prevention and treatment of venous thromboembolic and coronary thrombotic events. It could allow (if confirmed by clinical trials) a complete oral treatment of deep vein thrombosis without any biological monitoring. Melagatran is also active in the prevention of arterial thromboembolic events on atrial fibrillation. But other molecular forms of synthetic orally active direct antithrombin are also in development. Besides these important changes in our therapeutics which should appear in a near future, molecules aimed at other target are also tested: the most advanced are those antagonizing the initial phase of tissue factor activation of factor VII but other strategies are being tested such as stimulation of fibrinolysis. These new drugs at our disposal to treat venous thromboembolism should modify completely our handling of the patients. But additionally the numerous clinical trials necessary to prove the efficacy of the drugs, modify our understanding in the implication of the coagulation and in the physiopathogeny of thrombotic events.

Topics: Administration, Oral; Azetidines; Benzylamines; Clinical Trials as Topic; Coronary Thrombosis; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Glycine; Hirudin Therapy; Humans; Orthopedics; Polysaccharides; Prodrugs; Prothrombin; Research; Thrombin; Thromboembolism; Time Factors; Venous Thrombosis

To review clinical information related to fondaparinux, a synthetic pentasaccharide recently approved for the prevention of deep-vein thrombosis (DVT) in patients undergoing major orthopedic surgeries and for extended DVT prophylaxis after hip fracture surgery.. Primary and review articles were identified by MEDLINE (1983-June 2003) using the key words pentasaccharide, Org31540, SR90107A, DVT prophylaxis, and fondaparinux. Additional sources were found listed in articles, abstracts, and unpublished data on file from the manufacturer. Articles selected were based on their coverage of the pharmacology, pharmacokinetics, safety, and efficacy of fondaparinux.. All of the articles identified were evaluated and all information deemed relevant was included.. Fondaparinux is a selective antithrombin-dependent, indirect inhibitor of activated factor Xa. It has a favorable and predictable pharmacokinetic profile when administered subcutaneously, and has a long half-life, allowing once-daily dosing. Fondaparinux lacks in vitro cross-reactivity with heparin-induced antibodies. Major Phase III studies have demonstrated that subcutaneous fondaparinux sodium 2.5 mg given at least 6 hours postoperatively resulted in a 55% reduction in the risk of venous thromboembolism (VTE) in patients undergoing hip fracture surgery, total hip replacement surgery, or knee replacement surgery compared with standard enoxaparin therapy. It has a safety profile similar to that of enoxaparin with respect to clinically relevant major bleeding, including fatal bleeding, nonfatal bleeding, and bleeding requiring repeat surgery. The use of fondaparinux for prolonged prophylaxis after hip fracture has demonstrated further reduction in VTE events without increasing the risk of bleeding.. Fondaparinux is the first of a new class of synthetic factor Xa inhibitors that demonstrated greater efficacy compared with enoxaparin for the prevention of VTE in major orthopedic surgery without an increase in clinically relevant bleeding. Given the favorable cost-effectiveness analysis and improved efficacy profile, fondaparinux should be considered for formulary addition for DVT prophylaxis in patients undergoing hip and knee replacement surgery. In patients undergoing hip fracture surgery, fondaparinux should be considered the DVT prophylaxis of choice. Extended thromboprophylaxis up to 28 days resulted in additional reduction in VTE (both symptomatic and venography-proven DVT) in patients with hip fracture surgery.

Topics: Adult; Aged; Factor Xa Inhibitors; Female; Fondaparinux; Formularies as Topic; Humans; Male; Middle Aged; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Randomized Controlled Trials as Topic; Thromboembolism; Venous Thrombosis

Treatment of deep venous thrombosis is founded on the association of low molecular heparins and oral anticoagulants for 3-6 months. In spite of their uncontested efficacy, these therapeutics bring an hemorrhagic risk and the need of regular laboratory controls for the whole duration of the treatment. The clinical need to extend the indications of anticoagulants have made necessary the development of new antithrombotic treatments.. Two new molecules, fondaparinux and ximelagatran, have been recently developed and are, at present, in very advanced phase of clinical research. Already published phase III studies on venous thromboembolism (VTE) prophylaxis show the efficacy of these new molecules towards this indication. The results of phase III study in patients with acute VTE have not been published yet.. The new anticoagulant molecules fondaparinux and ximelagatran could open the way to new therapeutic possibilities that could simplify the managing of patients under anticoagulant treatment.

Topics: Anticoagulants; Azetidines; Benzylamines; Clinical Trials as Topic; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Treatment Outcome; 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

Fondaparinux is the first of a new class of antithrombotic compounds, the synthetic pentasaccharides. By binding rapidly and strongly to antithrombin, its sole physiologic target in plasma, fondaparinux catalyzes specifically the inhibition of factor Xa, which results in effective and linear dose-dependent inhibition of thrombin generation. Fondaparinux does not bind to platelets. Its antithrombotic effect has been demonstrated in several animal models of arterial and venous thrombosis. At equivalent antithrombotic concentrations, fondaparinux induced less bleeding than unfractionated heparin in experimental bleeding models. Furthermore, it did not cross-react with sera from patients with heparin-induced thrombocytopenia. Administered subcutaneously, the absorption of fondaparinux is complete, rapid, and independent of dose. It has a linear pharmacokinetic profile, and its half-life of approximately 17 h allows for once-daily dosing. Fondaparinux is almost completely excreted by the kidneys. Owing to the limited intrasubject and intersubject variability, routine monitoring and dose adjustments should not be required for most patients. Fondaparinux has been approved for use in thromboprophylaxis after major orthopedic surgery, where it has demonstrated its efficacy compared to a low-molecular-weight heparin. Its clinical development in other indications is ongoing.

Topics: Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Humans; Polysaccharides; Postoperative Complications; Structure-Activity Relationship; Venous Thrombosis

Fondaparinux, a selective inhibitor of factor Xa, is the first of a new class of antithrombotic compounds, the synthetic pentasaccharides. Its benefit-to-risk ratio in preventing venous thromboembolism after major orthopedic surgery was investigated in four randomized, double-blind international phase III trials in patients undergoing surgery for hip fracture, elective hip replacement, and major knee surgery. Compared to enoxaparin, fondaparinux administered at a subcutaneous dose of 2.5 mg qd, starting postoperatively, reduced the overall incidence of venous thromboembolism up to day 11 by 55.2% (p < 0.001). The incidence of clinically relevant bleeding was low and did not differ between the two groups. Overall, fondaparinux achieved optimal efficacy and safety when treatment was initiated > or =6 h after the surgical procedure. In a further randomized double-blind trial, 4 weeks of prophylaxis with fondaparinux after hip fracture surgery reduced the risk of venous thromboembolism by 96% as compared to 1 week of prophylaxis, and was well tolerated. Fondaparinux has been recently approved for use in thromboprophylaxis after major orthopedic surgery. The clinical development of fondaparinux in other thromboprophylactic indications is ongoing.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Enoxaparin; Factor Xa Inhibitors; Fondaparinux; Humans; Polysaccharides; Postoperative Complications; Randomized Controlled Trials as Topic; Venous Thrombosis

Adjusted doses of oral warfarin sodium or fixed doses of subcutaneous low-molecular-weight heparin (LMWH) are the standard approaches for preventing venous thromboembolism following major orthopedic surgery of the legs. In recent years, new anticoagulants have been compared with either LMWH or warfarin. The optimal timing for the first dose of LMWH prophylaxis and of the new anticoagulants is controversial. Recent clinical trials of LMWH and of newer anticoagulants have provided new information on the relationship between the timing of the first anticoagulant dose and the efficacy and safety of thromboprophylaxis after major orthopedic surgery. These data on the optimal timing of initiating prophylaxis come from limited direct randomized comparisons of different timing with the same anticoagulant, subgroup analysis of large studies with a single anticoagulant, indirect comparisons across studies in systematic reviews, and single randomized trials comparing different anticoagulants. In the direct comparison of the same anticoagulant, preoperative initiation of the same regimen of LMWH (dalteparin) increased major bleeding, without improved antithrombotic efficacy compared to the early postoperative regimen. Fondaparinux, 2.5 mg, begun 6 h postoperatively is more effective and as safe as the currently approved regimens of enoxaparin begun either 12 h preoperatively, or 12 to 24 h postoperatively, in patients undergoing major orthopedic surgery. In a subgroup analysis of several large randomized trials, fondaparinux, 2.5 mg, begun < 6 h postoperatively was associated with increased major bleeding, without improved efficacy. The results of indirect comparisons also favor the use of a 6-h postoperative starting time for the first dose, while the single randomized trials comparing different anticoagulants performed to date are not helpful in establishing an optimal time for the first dose. The aggregate clinical research evidence supports the following general conclusions about the relationship between the timing of the first anticoagulant dose and the efficacy and safety of prophylaxis: (1) preoperative initiation is not required for good efficacy and, when begun within 2 h of surgery, increases major bleeding; (2) initiation at 6 h postoperatively is effective and not associated with increased major bleeding; (3) initiation < 6 h postoperatively increases major bleeding, without improved efficacy; thus, 6 h appears to be the threshold for early postoperative

Topics: Anticoagulants; Drug Administration Schedule; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Leg; Polysaccharides; Postoperative Complications; Randomized Controlled Trials as Topic; Time Factors; Venous Thrombosis; Warfarin

Venous thromboembolism (VTE) prophylaxis is indicated while in the hospital after major surgery. There is evidence that the prevalence of asymptomatic deep-vein thrombosis, detected by routine venography after major orthopedic surgery, is lower at hospital discharge in patients who have received 10 days rather than 5 days of prophylaxis. This observation supports the current American College of Chest Physicians (ACCP) recommendation for a minimum of 7 to 10 days of prophylaxis after hip and knee replacement, even if patients are discharged from the hospital within 7 days of surgery. As risk of VTE persists for up to 3 months after surgery, patients at high risk for postoperative VTE may benefit from extended prophylaxis (eg, an additional 3 weeks after the first 7 to 10 days). Extended prophylaxis with low-molecular-weight heparin (LMWH) reduces the frequency of postdischarge VTE by approximately two thirds after hip replacement; however, the resultant absolute reduction in the frequency of fatal pulmonary embolism is small (ie, estimated at 1 per 2,500 patients). Indirect evidence suggests that, compared with LMWH, efficacy of extended prophylaxis after hip replacement is greater with fondaparinux, similar with warfarin, and less with aspirin. Extended prophylaxis is expected to be of less benefit after knee than after hip replacement. In keeping with current ACCP recommendations, at a minimum, extended prophylaxis should be used after major orthopedic surgery in patients who have additional risk factors for VTE (eg, previous VTE, cancer). If anticoagulant drug therapy is stopped after 7 to 10 days, an additional month of prophylaxis with aspirin should be considered.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Drug Administration Schedule; Fondaparinux; Hemorrhage; Heparin; Humans; Polysaccharides; Postoperative Complications; Prevalence; Radiography; Risk Factors; Time Factors; Venous Thrombosis; Warfarin

Despite widespread use of antithrombotic agents, major orthopedic surgery (total hip arthroplasty, major knee surgery, fracture of the femoral neck) still raises a high risk of deep vein thrombosis and pulmonary embolism. Proper understanding of thromboprophylaxis in orthopedic surgery requires good knowledge of the mechanisms of coagulation and the point of action of different antithrombotic agents. Sodium fondaparinux is the first synthetic inhibitor selective for factor Xa. It is composed of five saccharide units obtained by chemical synthesis, thus eliminating the risk of contamination by a pathogenic agent of animal origin and batch variability. Clinical trials using sodium fondaparinux for the prevention of venous thromboembolism after major orthopedic surgery have demonstrated its superiority over low-molecular-weight heparin without increased risk of clinically pertinent bleeding if the first injection is given at the proper time. We present the main results of clinical trials.

Topics: Clinical Trials as Topic; Factor Xa Inhibitors; Fondaparinux; Heparin; Humans; Orthopedic Procedures; Polysaccharides; Risk Factors; Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Fondaparinux; Humans; Polysaccharides; Thromboembolism; Venous Thrombosis

Due to their favorable pharmacologic properties and beneficial clinical effects, low molecular weight heparins (LMWHs) have become the standard of care in the prevention and treatment of venous thromboembolism and have also been extensively studied in the treatment of acute coronary syndromes. Pentasaccharide is the first of a new class of synthetic antithrombotics and has been shown to be superior to LMWH in preventing deep vein thrombosis. Hirudin is the most potent direct thrombin inhibitor and has provided superior antithrombotic efficacy when compared with LMWH. In acute coronary syndromes, however, the antithrombotic activity of hirudin has been compromised by a significant increase in major hemorrhage.

Topics: Angina, Unstable; Anticoagulants; Clinical Trials as Topic; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hirudin Therapy; Humans; Myocardial Infarction; Polysaccharides; Venous Thrombosis

Fondaparinux sodium is the first in a new class of antithrombotic agents possessing selective inhibitory activity against factor Xa. The agent was designed and developed with the objective of overcoming the limitations of currently available therapies for the prevention and treatment of venous and arterial thromboembolic disease. Extensive data from preclinical and clinical trials demonstrate fondaparinux's favorable pharmacokinetic profile combined with promising efficacy and safety results in the prevention of venous thromboembolism following major orthopedic surgery, in the treatment of deep venous thrombosis, and in acute coronary syndromes.

Topics: Animals; Factor Xa Inhibitors; Fondaparinux; Humans; Oligosaccharides; Polysaccharides; Thromboembolism; Venous Thrombosis

Venous thromboembolism (VTE) is a life-threatening complication following orthopedic surgery. Selective factor Xa inhibition is a new antithrombotic approach designed to avoid difficulties associated with heparins and other current anticoagulants. Several antifactor Xa compounds are in early investigation, but fondaparinux (Arixtra; NV Organon, Oss, The Netherlands; Sanofi-Synthelabo, Paris, France) is the first and most advanced compound in the development of a new class of synthetic antithrombotic agents--the selective factor Xa inhibitors. Fondaparinux has a highly favorable pharmacokinetic profile; four large phase 3 trials comparing subcutaneous fondaparinux 2.5 mg once daily with the low molecular weight heparin (LMWH) enoxaparin in doses approved by regulatory bodies showed that fondaparinux reduced the overall risk of VTE in major orthopedic surgery by > 50% without increasing clinically relevant bleeding. Fondaparinux also appears to be a very promising candidate for the treatment of patients with existing VTE.

Topics: Animals; Anticoagulants; Clinical Trials, Phase III as Topic; Enoxaparin; Factor Xa Inhibitors; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Orthopedic Procedures; Polysaccharides; Thromboembolism; Venous Thrombosis

Orthopedic surgery remains a condition at high risk of venous thromboembolism (VTE). Fondaparinux, the first of a new class of synthetic selective factor Xa inhibitors, may further reduce this risk compared with currently available thromboprophylactic treatments.. A meta-analysis of 4 multicenter, randomized, double-blind trials in patients undergoing elective hip replacement, elective major knee surgery, and surgery for hip fracture (N = 7344) was performed to determine whether a subcutaneous 2.5-mg, once-daily regimen of fondaparinux sodium starting 6 hours after surgery was more effective and as safe as approved enoxaparin regimens in preventing VTE. The primary efficacy outcome was VTE up to day 11, defined as deep vein thrombosis detected by mandatory bilateral venography or documented symptomatic deep vein thrombosis or pulmonary embolism. The primary safety outcome was major bleeding.. Fondaparinux significantly reduced the incidence of VTE by day 11 (182 [6.8%] of 2682 patients) compared with enoxaparin (371 [13.7%] of 2703 patients), with a common odds reduction of 55.2% (95% confidence interval, 45.8% to 63.1%; P<.001); this beneficial effect was consistent across all types of surgery and all subgroups. Although major bleeding occurred more frequently in the fondaparinux-treated group (P =.008), the incidence of clinically relevant bleeding (leading to death or reoperation or occurring in a critical organ) did not differ between groups.. In patients undergoing orthopedic surgery, 2.5 mg of fondaparinux sodium once daily, starting 6 hours postoperatively, showed a major benefit over enoxaparin, achieving an overall risk reduction of VTE greater than 50% without increasing the risk of clinically relevant bleeding.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Confidence Intervals; Double-Blind Method; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Fracture Fixation, Internal; Hip Fractures; Humans; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Orthopedic Procedures; Polysaccharides; Randomized Controlled Trials as Topic; Thromboembolism; Time Factors; Treatment Outcome; Venous Thrombosis

Traditional and modern anticoagulant therapies for the management, prophylaxis, and treatment of venous thromboembolism (VTE) and acute coronary syndrome (ACS) and key findings of primary studies are summarized. Significant advances have been made during the past decade in the prevention and treatment of VTE and the treatment of ACS. Numerous trials have demonstrated that low-molecular-weight heparins (LMWHs) are at least as effective as and have challenged unfractionated heparins (UFHs) as the standard of care for the treatment of VTE and ACS. For VTE, a number of new antithrombotic agents have been developed and are currently under development, including oral direct thrombin inhibitors and synthetic pentasaccharides, such as fondaparinux, in addition to LMWHs. For ACS, various new treatment modalities, such as the broader use of percutaneous transluminal coronary angioplasty and stents, are available, in addition to new pharmacologic agents, such as glycoprotein IIb/IIIa inhibitors and innovative thrombolytics. Most of these agents and treatment modalities require the use of an anticoagulant as adjuvant therapy. Evidence suggests that LMWHs can be used safely and, in addition to being more practical, have been shown to improve outcomes compared with traditional anticoagulants in certain patient populations. LMWHs demonstrate superior clinical outcomes over traditional anticoagulants for VTE prophylaxis and treatment and ACS treatment. Primary studies of new agents, including oral direct thrombin inhibitors and synthetic pentasaccharides for the treatment of ACS are promising; however, more data are needed on their safety and efficacy.

Topics: Anticoagulants; Azetidines; Benzylamines; Coronary Disease; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Thromboembolism; Venous Thrombosis

Fondaparinux is a promising new antithrombotic agent. This pentasaccharide selectively and specifically inhibits coagulation factor Xa, and requires antithrombin as co-factor It is entirely synthetic, in contrast to conventional heparin and low molecular heparins which are derived from animal tissues. Fondaparinux exhibits a high bioavailability and is convenient to use as it only needs to be given once daily by subcutaneous injection. Peak plasma levels are achieved within two hours of dosing and the plasma half-life of fondaparinux is approximately 17 hours. There is no specific antidote for fondaparinux: it is not neutralised by protamine sulphate. Fondaparinux shows no cross-reactivity with antibodies associated with heparin-induced thrombocytopenia. Several randomised, double-blind studies have demonstrated superiority with respect to a low molecular weight heparin (enoxaparin) in preventing venous thromboembolism in the setting of orthopaedic surgery. The results of clinical trials of fondaparinux in the treatment of deep vein thrombosis and acute coronary syndrome are also presented.

Topics: Anticoagulants; Female; Fondaparinux; Heart Diseases; Humans; Male; Polysaccharides; Randomized Controlled Trials as Topic; Treatment Outcome; Venous Thrombosis

The synthetic pentasaccharide fondaparinux is the first in a novel class of antithrombotic agents. By selectively inactivating factor Xa in an antithrombin-dependent mechanism of action, fondaparinux exerts its anticoagulant effect through inhibition of thrombin generation, without any direct effect on thrombin activity. Unlike unfractionated heparin and low-molecular-weight heparins, fondaparinux is a single molecular entity produced by total chemical synthesis. Its favorable pharmacokinetic profile and pharmacodynamics allow for safe and effective once-daily dosing in the majority of populations. Initial clinical development of fondaparinux has focused on the prevention of venous thromboembolism following major orthopedic surgery--that is, hip and knee replacement and hip fracture. Results of the largest phase III clinical trial program to date in these major hip and knee surgeries demonstrate comparable safety, in terms of clinically relevant bleeding, and an overall 55% reduction in risk of venous thromboembolism with fondaparinux relative to the low-molecular-weight heparin enoxaparin.

Topics: Anticoagulants; Factor Xa Inhibitors; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Randomized Controlled Trials as Topic; Thromboembolism; Venous Thrombosis

Venous thrombosis is usually triggered by a low-flow state, as in prolonged periods of bed rest after hip or knee surgery. Antithrombotic agents are the drugs of choice in such circumstances. The new factor Xa inhibitor fondaparinux has been approved by the US Food and Drug Administration for the prevention of venous thromboembolism in patients undergoing hip fracture surgery, hip replacement surgery, or knee replacement surgery.. The aim of this article was to review the clinical pharmacology of fondaparinux and summarize the data from available clinical trials of this agent.. The terms fondaparinux, SR90107A/ORG31540, and factor Xa were used to search MEDLINE and Current Contents/Clinical Medicine for English-language studies in humans published between 1996 and May 2002. Unpublished data were provided by the manufacturer of fondaparinux, and additional information was obtained from abstracts presented at the 2001 congress of the International Society on Thrombosis and Haemostasis in Paris.. Fondaparinux is a synthetic pentasaccharide that selectively binds to antithrombin III, inducing a conformational change that increases anti-factor Xa activity. Phase III studies to date have reported that fondaparinux had greater efficacy compared with enoxaparin in terms of prevention of venous thromboembolism after hip or knee replacement surgery. Preliminary studies have suggested that this agent may have efficacy in the treatment of deep vein thrombosis, as well as in the management of acute coronary syndromes. However, 1 study reported a significant increase in the risk of major bleeding with fondaparinux compared with enoxaparin (2.1% vs 0.2%, respectively; P = 0.006), and another reported a significant increase in the risk of minor bleeding (4.1% vs 2.1%; P = 0.02).. Fondaparinux has shown efficacy in the prevention of venous thromboembolism in patients undergoing hip or knee replacement surgery. Large-scale clinical trials of its potential efficacy in deep vein thrombosis and acute coronary syndromes are ongoing. Use of fondaparinux may be associated with an increased bleeding risk, and patients should be assessed individually to ensure that the possible benefits outweigh the risks. Routine use of fondaparinux as a replacement for low-molecular-weight heparin is not recommended at this time.

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Clinical Trials as Topic; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Humans; MEDLINE; Polysaccharides; Postoperative Complications; Treatment Outcome; Venous Thrombosis

Fondaparinux (Org-31540 / SR-90107A) is a new drug chemically synthesized for treatment and prophylaxis of thromboembolic disease. Fondaparinux is a selective inhibitor of activated factor X. Its structure is the copy of the heparin pentasaccharide sequence, the shortest chain required for antithrombin inhibition of activated factor X without antithrombin action. Fondaparinux has no effect on coagulation tests and does not bind to platelet factor 4 or promote heparin-induced thrombocytopenia. Fondaparinux inhibits thrombin generation and the growth of thrombi in in vitro and in vivo models. Phase I trials have shown a 100% bioavailability after subcutaneous (s.c.) administration, a rapid onset of action and an approximate half-life of 13.5 h. Fondaparinux is cleared as an active substance by the kidneys. In elderly patients, renal clearance is reduced and the half-life is longer. The phase II Pentathlon trial demonstrated significant dose-dependent reductions in the frequency of venous thromboembolism in total hip-replacement patients and the optimal dose was determined to be 2.5 mg s.c./24 h. Four phase III trials have evaluated fondaparinux starting 6 hours after surgery compared with enoxaparin for prevention of venous thromboembolism following orthopedic surgery in 7,344 patients. The risk of thrombosis was reduced by 50% with fondaparinux and no differences were observed in death or severe bleeding. In a phase II trial, similar efficacy and incidence of major bleeding were seen with fondaparinux s.c. compared with dalteparin s.c. in the treatment of deep venous thrombosis. In patients with acute myocardial infarction, the efficacy of fondaparinux during fibrinolytic therapy was assessed in 326 patients who had acute coronary syndromes of less than a 6 hour duration, showing a slight but statistically not significant advantage for fondaparinux over unfractionated heparin in the coronary angiographies. There is currently no antidote for fondaparinux.

Topics: Animals; Blood Coagulation; Fibrinolytic Agents; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Thromboembolism; Thrombosis; Vascular Diseases; Venous Thrombosis

A worldwide phase III program, consisting of four randomized, double-blind trials in patients undergoing surgery for hip fracture, in elective hip replacement surgery patients and in elective major knee surgery patients, was conducted to compare the benefit-to-risk ratio of a subcutaneous 2.5-mg once-daily regimen of fondaparinux, a synthetic selective factor Xa inhibitor, starting postoperatively with enoxaparin in preventing venous thromboembolism. The overall incidence of venous thromboembolism up to day 11 was reduced from 13.7% in the enoxaparin group to 6.8% in the fondaparinux group with a common odds reduction of 55.2% in favor of fondaparinux (95% confidence interval: 45.8-63.1%, p = 10(-17)). This superior efficacy of fondaparinux was also demonstrated for proximal deep vein thrombosis with a reduction of 57.4%. The overall incidence of clinically relevant bleeding was low and did not differ between the two groups. The benefit of fondaparinux was consistent across all types of surgery and all subgroups.

Topics: Adolescent; Adult; Aged; Anticoagulants; Enoxaparin; Fondaparinux; Humans; Middle Aged; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Safety; Treatment Outcome; Venous Thrombosis

Traditional anticoagulant drugs including vitamin K antagonists and heparins have several limitations. Despite their use, the burden of venous thromboembolism remains high, particularly in patients undergoing major orthopedic surgery. A new strategy for the design of new antithrombotic drugs is based on selective inhibition of a specific coagulation factor. Fondaparinux is a synthetic selective inhibitor of factor Xa, which is critically positioned at the start of the common pathway of the coagulation system. Its pharmacokinetic profile allows for once-daily administration without the need for laboratory monitoring or dose adjustment. Fondaparinux has demonstrated its efficacy compared to a widely used low-molecular-weight heparin in a number of thromboprophylaxis trials after major orthopedic surgery and is approved for use in this setting.

Topics: Anticoagulants; Factor Xa Inhibitors; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Venous Thrombosis

Fondaparinux (Arixtra, Sanofi-Synthélabo/Organon) is the first of a new class of antithrombotic agents distinct from low molecular weight heparins (LMWHs) and heparin. It is a chemically synthetic pentasaccharide mimicking the site of heparin that binds to antithrombin III (AT). It exhibits only factor (F) Xa (FXa) inhibitor activity via binding to AT, which in turn inhibits thrombin generation. In contrast to heparin and LMWH, plasma anti-Xa activity corresponds directly to levels of fondaparinux. It does not release tissue factor pathway inhibitor (TFPI). There is nearly complete bioavailability by the sc. route, rapid onset of action, a prolonged half-life in both iv. and sc. (14 - 20 h) dosing regimens and no metabolism preceding renal excretion. Phase IIb clinical studies have identified a dose of 2.5 mg once-daily for prophylaxis of venous thrombosis. Four Phase III studies (n > 7000) have demonstrated a combined 50% relative risk reduction of venous thromboembolic events in orthopaedic surgery patients in comparison to the LMWH, enoxaparin. Haemmorrhagic complications for fondaparinux were either comparable to or higher than those for LMWH. The activated partial thromboplastin time (aPTT) is not affected by fondaparinux. At present, laboratory monitoring is not recommended. Clinical trials for treatment of established thrombosis, coronary syndromes and adjunct to thrombolytic therapy are in progress.

Topics: Animals; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Treatment Outcome; Venous Thrombosis

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

Topics: Clinical Trials, Phase III as Topic; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Polysaccharides; Survival Rate; Therapeutic Equivalency; Thromboembolism; Treatment Outcome; Venous Thrombosis

Nattokinase (NK) is a serine protease enzyme with fibrinolytic activity. Even if it could be used for the treatment of several diseases, no data have been published supporting its use patients who underwent vascular surgery. In this study, we evaluated both the efficacy and the safety of nattokinase (100 mg/day per os) in patients admitted to vascular surgery. Patients were of both sexes, >18 years of age, with vascular diseases (i.e., deep vein thrombosis, superficial vein thrombosis, venous insufficiency), and naïve to specific pharmacological treatments (anticoagulants or anti-platelets). Patients were divided into three groups. Group 1: patients with deep vein thrombosis, treated with fondaparinux plus nattokinase. Group 2: patients with phlebitis, treated with enoxaparin plus nattokinase. Group 3: patients with venous insufficiency after classical surgery, treated with nattokinase one day later. During the study, we enrolled 153 patients (age 22-92 years), 92 females (60.1%) and 61 males (39.9%;), and documented that nattokinase was able to improve the clinical symptoms (

Topics: Adult; Aged; Aged, 80 and over; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Humans; Male; Middle Aged; Subtilisins; Vascular Surgical Procedures; Venous Insufficiency; Venous Thrombosis; Young Adult

We aimed to assess the safety and efficacy of fondaparinux (FPNX) for patients undergoing laparoscopic colorectal surgery (LAC).. Patients scheduled for LAC received once-daily subcutaneous injections of FPNX 1.5-2.5 mg for 4-8 days. The primary endpoint was the incidence of bleeding events. The secondary endpoint was the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE).. Among 128 patients evaluable for efficacy, 119 patients were administered FPNX. Nine patients were excluded owing to intraoperative events, including conversion to open surgery among others. Thirteen patients discontinued treatment owing to anastomotic bleeding (n = 5), anastomotic leakage (n = 3), bleeding at drain insertion site (n = 2), subcutaneous bleeding (n = 1), drug-induced rash (n = 1), and sepsis (n = 1). Among the FPNX discontinuations, there were eight cases of bleeding (6.7%), and two cases of major bleeding (1.7%). In multivariate analysis, operative time >300 min was identified as a risk factor for bleeding events (p = 0.001) secondary to FPNX. The incidence rate of DVT was 2.5% (3/119 cases); these patients were asymptomatic.. There were no cases of PE. It is necessary to establish strict criteria for VTE prophylaxis with FPNX after LAC for Japanese patients considering the incidence of bleeding events.

Topics: Adult; Aged; Aged, 80 and over; Colorectal Neoplasms; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Humans; Laparoscopy; Male; Middle Aged; Polysaccharides; Postoperative Complications; Prospective Studies; Thromboembolism; Venous Thrombosis

XALIA assessed the safety and effectiveness of rivaroxaban for deep vein thrombosis (DVT) treatment in routine clinical practice. This substudy describes the clinical characteristics and outcomes of 'early switchers' - patients who received heparin or fondaparinux for >2-14days and/or a vitamin K antagonist (VKA) for 1-14days before switching to rivaroxaban.. Patients with DVT (latterly with concomitant pulmonary embolism) received rivaroxaban or standard anticoagulation (initial treatment with heparin or fondaparinux, usually overlapping with and followed by a VKA). Patients administered rivaroxaban alone, or heparin or fondaparinux for ≤48h pre-enrollment were included in the rivaroxaban cohort. Therapy type, dose, and duration were at the physician's discretion. Primary outcomes were major bleeding, recurrent venous thromboembolism (VTE), and all-cause mortality.. In 368 early switchers, recurrence or bleeding risk factors were more prevalent versus the rivaroxaban cohort, including creatinine clearance<50mL/min (6.5% vs. 3.9%), previous major bleeding (4.6% vs. 1.4%), active cancer (8.2% vs. 5.6%), and concomitant pulmonary embolism (20.9% vs. 8.4%). Crude incidence rates were numerically higher versus the rivaroxaban cohort for major bleeding (1.4% vs. 0.7%), recurrent VTE (2.2% vs. 1.4%), and all-cause mortality (0.8% vs. 0.5%).. Patients who switched to rivaroxaban early in the treatment process had a higher frequency of risk factors for bleeding and recurrent VTE than patients treated with rivaroxaban; reflected by the higher risk of adverse events in that group during follow-up.

Topics: Adult; Aged; Anticoagulants; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Middle Aged; Polysaccharides; Rivaroxaban; Treatment Outcome; Venous Thrombosis

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

The immobilisation of the lower leg is associated with deep vein thrombosis (DVT). However, thromboprophylaxis in patients with a below-knee plaster cast remains controversial. We examined the efficacy and safety of nadroparin and fondaparinux to ascertain the need for thromboprophylaxis in these patients.. PROTECT was a randomised, controlled, single-blind, multicentre study that enrolled adults with an ankle or foot fracture who required immobilisation for a minimum of four weeks. The patients were randomly assigned (1:1:1) to a control group (no thromboprophylaxis) or to one of the intervention groups: daily subcutaneous self-injection of either nadroparin (2850 IE anti-Xa=0.3ml) or fondaparinux (2.5mg=0.5ml). A venous duplex sonography was performed after the removal of the cast or earlier if thrombosis was suspected. The primary outcome was the relative risk of developing DVT in the control group compared with that in both intervention groups. This trial is registered at ClinicalTrials.gov, number NCT00881088.. Between April 2009 and December 2015, 467 patients were enrolled and assigned to either the nadroparin group (n=154), the fondaparinux group (n=157), or the control group (n=156). A total of 273 patients (92, 92, and 94 patients, respectively) were analysed. The incidence of DVT in the nadroparin group was 2/92 (2.2%) compared with 11/94 (11.7%) in the control group, with a relative risk of 5.4 (95% CI 1.2-23.6; p=0.011). The incidence of DVT in the fondaparinux group was 1/92 (1.1%), yielding a relative risk of 10.8 (95% CI 1.4-80.7; p=0.003) compared with that in the control group. No major complications occurred in any group.. Thromboprophylaxis with nadroparin or fondaparinux significantly reduces the risk of DVT in patients with an ankle or foot fracture who were treated in a below-knee cast without any major adverse events.

Topics: Adult; Anticoagulants; Casts, Surgical; Female; Fondaparinux; Humans; Immobilization; Leg Injuries; Male; Middle Aged; Nadroparin; Polysaccharides; Postoperative Complications; Prospective Studies; Single-Blind Method; Treatment Outcome; Venous Thrombosis

Patients with superficial vein thrombosis (SVT) are commonly treated with low-molecular weight heparin or fondaparinux in prophylactic, intermediate or therapeutic dosages for treatment periods of 10-45 days. This practice is also reflected by the current guideline recommendations. However, given the broad range of thromboembolic complication rates in SVT (between 0 and 30 % have been reported) it seems reasonable to suspect that risk stratification is needed to differentiate patients at low risk who may not benefit from anticoagulation from those at high risk who may need higher dosages or a longer duration of anticoagulation. Furthermore, prolonged treatment with injectable anticoagulants has been shown to result in poor patient adherence. Direct oral anticoagulants have recently been approved for venous thromboembolism therapy and these new drugs may offer advantages also for SVT patients. The prospective, randomized, open-label, blinded adjudication trial superficial phlebitis treated for 45 days with rivaroxaban versus fondaparinux (SURPRISE) will evaluate the efficacy and safety of 10 mg rivaroxaban OD compared to fondaparinux 2.5 mg OD for SVT treatment in a subset of high-risk SVT patients over a treatment period of 45 days. The purpose of the study is to demonstrate non-inferiority of rivaroxaban compared to fondaparinux in preventing the combined efficacy endpoint of thrombus progression, SVT recurrence, DVT, PE and death. The results of the SURPRISE trial will provide evidence for the concept of risk stratification in SVT and for the value of rivaroxaban 10 mg in SVT treatment (clinicaltrials.gov NCT01499953).

Topics: Disease Progression; Fondaparinux; Humans; Polysaccharides; Recurrence; Risk Assessment; Rivaroxaban; Single-Blind Method; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

To compare the effects and side-effects of fondaparinux sodium and low molecular weight heparin in patients with hypercoagulability accompanied with traumatic infection.. Thirty-six patients with post-traumatic infections in our hospital intensive care center were diagnosed with hypercoagulability from February 2012 to February 2013. These patients were randomly divided into 2 groups. In group F (18 patients), the patients were treated with fondaparinux sodium, 2.5 mg, 1/d for 11 d. In group L (18 patients), the patients were treated with low molecular weight heparin, 4100 U, 1/12 h for 11 d. The incidence of deep vein thrombosis, bleeding events and multiple organ dysfunction syndrome (MODS) and mortality of two groups after anticoagulation therapy were analyzed. Fibrinogen, D-dimer level and activity of antithrombin III were measured by the coagulation analyzer.. The incidence of deep vein thrombosis, MODS incidence and mortality were not significantly different between the two groups. The rate of bleeding evens in group F was lower than group L (p < 0.05). Antithrombin III got an upward trend after anticoagulant therapy, in which it was higher in group F than in group L on the 5th d and 11th d (p<0.05). Fibrinogen levels were gradually increased, and there was no significant difference between two groups (p>0.05). D-dimer was significantly decreased after anticoagulant therapy for 5 d (p<0.01), and there were significant differences between two groups on the 5th d and 7th d (p<0.05). It showed no significant difference on the 11th d (p>0.05).. Fondaparinux sodium and low molecular weight heparin can effectively improve coagulopathy in patients with traumatic infection. Compared with low molecular weight heparin, fondaparinux sodium may reduce the risk of bleeding events in patients with hypercoagulability accompanied by traumatic infection.

Topics: Adult; Aged; Female; Fibrin Fibrinogen Degradation Products; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Infections; Male; Middle Aged; Multiple Organ Failure; Polysaccharides; Thrombophilia; Venous Thrombosis; Wounds and Injuries

The clinical relevance of symptomatic extension of spontaneous, acute, symptomatic, lower-limb superficial-vein thrombosis (SVT) is debated. We performed a post hoc analysis of a double-blind trial comparing fondaparinux with placebo. The main study outcome was SVT extension by day 77, whether to ≤ 3 cm or > 3 cm from the sapheno-femoral junction (SFJ). All events were objectively confirmed and validated by an adjudication committee. With placebo (n = 1500), symptomatic SVT extension to ≤ 3 cm or > 3 cm from the SFJ occurred in 54 (3.6%) and 56 (3.7%) patients, respectively, inducing comparable medical resource consumption (eg, anticoagulant drugs and SFJ ligation); subsequent deep-vein thrombosis or pulmonary embolism occurred in 9.3% (5/54) and 8.9% (5/56) of patients, respectively. Fondaparinux was associated with lower incidences of SVT extension to ≤ 3 cm (0.3%; 5/1502; P < .001) and > 3 cm (0.8%; 12/1502; P < .001) from the SFJ and reduced related use of medical resources; no subsequent deep-vein thrombosis or pulmonary embolism was observed in fondaparinux patients. Thus, symptomatic extensions are common SVT complications and, whether or not reaching the SFJ, are associated with a significant risk of venous thromboembolic complications and medical resource consumption, all reduced by fondaparinux.

Topics: Anticoagulants; Fondaparinux; Humans; Incidence; Placebos; Polysaccharides; Venous Thrombosis

The aim of this study was to estimate the effective administration procedure of fondaparinux for prevention of venous thromboembolism after cemented total hip replacement (THR) in Japanese patients. The study included 471 Japanese patients. The dose regimens were 2.5 mg daily for 14 days (2.5 mg/14 day group) or 10 days (2.5 mg/10 day group), 1.5 mg daily for 10 days (1.5 mg group), 2.5 mg daily for the first 3 postoperative days and 1.5 mg daily for the subsequent 7 days (Mixed group), and no administration of fondaparinux (Control group). Deep venous thrombosis (DVT) was diagnosed by ultrasonography on postoperative day 3 or 4 and day 14. The 2.5 mg/14 day, 2.5 mg/10 day and Mixed groups were regarded as one group in the assessment on postoperative day 3 or 4, and denoted as the 2.5 mg group. The incidence of DVT on postoperative day 3 or 4 in the 2.5 mg group was significantly lower than that in the Control and 1.5 mg groups. On postoperative day 14, the incidence of DVT in the 1.5 mg and Mixed groups was significantly lower than that in the Control group in both the intention-to-treat and per-protocol analyses. The incidence in the 2.5 mg/10 day and 2.5 mg/14 day groups was significantly lower than that in the Control group in only the per-protocol analysis. The results suggest that the administration protocol of the Mixed group is effective in preventing DVT in Japanese patients undergoing cemented THR.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Bone Cements; Cementation; Dose-Response Relationship, Drug; Female; Fondaparinux; Humans; Male; Middle Aged; Polysaccharides; Postoperative Complications; Time Factors; Ultrasonography; Venous Thrombosis

We evaluated hemostatic markers in patients who underwent major orthopedic surgery, including total hip and total knee arthroplasty, and were treated for the prophylaxis of deep vein thrombosis (DVT) with or without fondaparinux (anti-Xa group, n = 98 and without anti-Xa group, n = 20). The frequency of DVT was significantly higher in the without anti-Xa group than in the anti-Xa group, but the reduction of hemoglobin and fibrinolytic marker levels was significantly lower in the without anti-Xa group than in the anti-Xa group. Eighteen patients in the anti-Xa group showed a reduction in hemoglobin of more than 2 g/dl, and those individuals were considered to be the increased bleeding (IB) group. The concentration of fibrinolytic markers in the anti-Xa group was significantly higher in the IB group than in the non-IB group. There were also no significant differences in the levels of anti-Xa activity, plasminogen activator inhibitor-I, soluble fibrin and antithrombin between the IB and non-IB groups. In conclusion, elevated fibrinolysis induced by increased bleeding may lead to further increases in bleeding in patients receiving thromboprophylaxis with fondaparinux following major orthopedic surgery.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Biomarkers; Factor Xa Inhibitors; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fondaparinux; Hemorrhage; Humans; Male; Middle Aged; Polysaccharides; Postoperative Complications; Venous Thrombosis

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

The incidence of thromboembolic disease is increasing in children. New anticoagulants have been licensed in adults and need to be studied in children. This report describes the first prospective study of fondaparinux in children.. The purpose of the study was to determine the dosing, pharmacokinetics, and safety of fondaparinux in children with deep vein thrombosis (DVT) or heparin-induced thrombocytopenia (HIT). Hospitalized children between 1 and 18 years of age with DVT or HIT received fondaparinux 0.1 mg/kg once daily. Fondaparinux-based anti-factor Xa levels were assessed at 2, 4, 12, and 24 hr following the first dose, and peak levels were measured twice weekly thereafter. Detailed pharmacokinetic analyses were performed.. Twenty four subjects in 3 age cohorts were enrolled and completed the study. Pharmacokinetic modeling demonstrated that a once-daily dose of fondaparinux at 0.1 mg/kg resulted in similar concentrations known to be efficacious in adults. Safety was demonstrated with only two bleeding events: one which may have pre-dated study drug administration and one which led only to temporary discontinuation of study drug.. Dosing of fondaparinux at 0.1 mg/kg once daily in children resulted in PK profiles comparable to those in adults receiving standard dosing. Fondaparinux can be considered an attractive alternative to LMWH given its once-daily dosing, acceptable safety data, and other favorable properties.

Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Fondaparinux; Heparin; Humans; Infant; Polysaccharides; Thrombocytopenia; Time Factors; Venous Thrombosis

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

There are many reports concerning fondaparinux prophylaxis of asymptomatic deep vein thrombosis (DVT) after total hip arthroplasty (THA) or total knee arthroplasty (TKA), but little is known about the time course of aymptomatic DVT development during the administration of fondaparinux. The aim of the present study was to define the incidence and time course of aymptomatic DVT development during administration of fondaparinux, and to assess the efficacy of fondaparinux in resolving DVT.. We studied consecutive 71 patients who underwent THA surgery, and 30 patients who underwent TKA surgery with fondaparinux prophylaxis. Patients received once-daily subcutaneous injections of 2.5mg of fondaparinux for 14 days after surgery. DVT was diagnosed by ultrasonography, and it was scheduled on the day of surgery on day 1, day 4, and day 14 after surgery.. In patients who received fondaparinux for 14 days after THA surgery, the incidence of DVT was 0% on the day of the surgery, 13.6% at day 1, 27.1% at day 4, and 11.9% at day 14. In patients who received fondaparinux for 14 days after TKA surgery, the incidence of DVT was 4.2% on the day after surgery, 50.0% at day 1, 58.3% at day 4, and 20.8% at day 14. The incidence of DVT after THA or TKA surgery at day 14 was significantly reduced compared to that at day 4.. The incidence of asymptomatic DVT up to day 4 was high, but with 14 days continued treatment of fondaparinux, the incidence of asymptomatic DVT occurring at postoperative day 4 was significantly reduced at day 14.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Female; Fondaparinux; Humans; Incidence; Male; Middle Aged; Polysaccharides; Ultrasonography; Venous Thrombosis

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

Hip fracture surgery (HFS) carries a high risk of venous thromboembolism (VTE) in the absence of thromboprophylactic treatment. Previous reports have suggested that fondaparinux sodium (FPX) administration decreases the incidence of VTE after HFS and total hip and knee arthroplasties. However, investigations of that effect in Japanese populations remain inadequate. We evaluated the efficacy of FPX after HFS in a prospective randomized controlled trial.. Subjects comprised 76 consecutive Japanese patients who underwent HFS and were randomly assigned to the FPX group, who received subcutaneous injections of FPX 2.5 mg/day for 14 days beginning the next after HFS, or the control group (non-FPX group). D-dimer values were measured on admission and 7 and 14 days after HFS. Subjects with D-dimer levels over the cutoff value (> 20 microg/ml on day 7) underwent enhanced computed tomography (CT) to evaluate the possibility of deep vein thrombosis (DVT) of the lower extremities. D-dimer values, the incidence of DVT, and side effects associated with a bleeding tendency (i.e., hematoma or massive bleeding) were compared between groups.. The FPX group showed significantly lower D-dimer levels than the non-FPX group at 7 and 14 days after HFS (P < 0.05). Only one case in the FPX group exceeded the D-dimer cutoff compared to 12 cases in the non-FPX group (P = 0.001). DVTs were found with enhanced CT in one case in the FPX group and in five cases in the non-FPX group. In the FPX group, symptomatic hematoma at the surgical site and/or decreased hemoglobin > 2 g/dl was noted in four cases (10.5%). Postoperative drainage volumes did not differ significantly between groups.. FPX administration demonstrated positive effects on the prevention of VTE after HFS. However, careful postoperative observation is warranted to prevent serious side effects after FPX administration.

Topics: Aged; Aged, 80 and over; Anticoagulants; Female; Fibrin Fibrinogen Degradation Products; Fondaparinux; Fracture Fixation; Hip Fractures; Humans; Japan; Male; Polysaccharides; Venous Thromboembolism; Venous Thrombosis

Heparin-induced thrombocytopenia (HIT) is a life-threatening immune response to heparin that is associated with a high risk of thromboembolic complications. We prospectively treated seven subjects with acute HIT with fondaparinux and compared the results to a similar historical control population from the same hospital. Six of the seven fondaparinux-treated subjects were transitioned to warfarin, beginning after platelet count recovery occurred. Ten historical controls were treated with a direct thrombin inhibitor (DTI), eight of which were transitioned to warfarin. The primary study outcome was platelet count recovery which was defined as an increase from baseline by at least 30% of nadir to greater than 100,000/mm(3) by day seven. Seven subjects were prospectively treated with fondaparinux for a median of eight days. Six of the seven had HIT with thrombosis at the time of enrollment. All fondaparinux treated subjects had a complete platelet count recovery, and none experienced a new thromboembolic complication, major bleeding or death by week four. One subject underwent limb amputation. Ten historical controls were treated with a DTI for a median duration of eleven days. Platelet count recovery occurred in eight of the ten historical controls. No new thromboembolic complications or major bleeds occurred but limb gangrene occurred in four controls. The development of limb gangrene in the historical controls may have been a result of delayed recognition of HIT and/or inappropriately early institution of warfarin in the historical controls. This pilot study suggests that fondaparinux may be useful in patients with acute HIT.

Topics: Acute Disease; Aged; Anticoagulants; Blood Coagulation; Case-Control Studies; Factor Xa Inhibitors; Feasibility Studies; Female; Fondaparinux; Hemorrhage; Heparin; Humans; International Normalized Ratio; Male; Pilot Projects; Platelet Count; Polysaccharides; Prospective Studies; Thrombocytopenia; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Selecting initial anticoagulant dose by patient weight for acute pulmonary embolism and deep vein thrombosis has clinical credibility; however, uncertainty remains regarding how to dose obese patients with newer anticoagulants because outcome data are sparse.. To use the Matisse trials' comparison of sc fondaparinux once daily with control heparin therapies (intravenous unfractionated heparin for pulmonary embolism, sc enoxaparin 1 mg/kg b.i.d. for deep vein thrombosis) for initial treatment in order to compare primary outcomes (venous thromboembolism recurrence and major bleeding) in obese patients.. Primary outcomes were compared in subsets composed of patients weighing < or = and > 100 kg and with body mass index (BMI) < 30 and > or = 30 kg/m(2). Medians and ranges for weight and BMI were compared for patients suffering either recurrence or major bleeding.. Twenty-two thousand and one patients received fondaparinux and 2217 received enoxaparin or unfractionated heparin. Four hundred and ninety-six patients (11%) weighed > 100 kg and 1216 (28%) had a BMI > or = 30. Treatment groups had similar characteristics. The upper limit in subject weight for recurrence was 166 kg (BMI 58), and for major bleeding 120 kg (BMI 39). The incidences of recurrence and major bleeding were similar for each patient subset of weight and BMI for both fondaparinux and heparin treatment groups. Among patients with a primary outcome, median weights and BMIs were also similar.. The current recommended doses of fondaparinux and heparins for the treatment of venous thromboembolism appear to provide similar protection against recurrence and major bleeding to one another and to obese and non-obese patients.

Topics: Adult; Aged; Anticoagulants; Enoxaparin; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Middle Aged; Obesity; Polysaccharides; Recurrence; Thromboembolism; Treatment Outcome; Venous Thrombosis

Little is known about the efficacy of graduated compression stockings in preventing venous thromboembolism after hip surgery. We conducted a prospective, randomised single-blind study to determine whether the addition of compression stockings to fondaparinux conferred any additional benefit. The study included 874 patients, of whom 795 could be evaluated (400 in the fondaparinux group and 395 in the fondaparinux plus compression stocking group). Fondaparinux was given post-operatively for five to nine days, either alone or combined with wearing stockings, which were worn for a mean 42 days (35 to 49). The study outcomes were venous thromboembolism, or sudden death before day 42. Duplex ultrasonography was scheduled within a week of day 42. Safety outcomes were bleeding and death from venous thromboembolism. The prevalence of deep-vein thrombosis was similar in the two groups 5.5% (22 of 400) in the fondaparinux group and 4.8 (19 of 395) in the fondaparinux plus stocking group (odds ratio 0.88, 95% confidence interval 0.46 to 1.65, p = 0.69). Major bleeding occurred in only one patient. The addition of graduated compression stockings to fondaparinux appears to offer no additional benefit over the use of fondaparinux alone.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Female; Fondaparinux; Hip Fractures; Humans; Male; Middle Aged; Polysaccharides; Postoperative Complications; Prospective Studies; Single-Blind Method; Stockings, Compression; Time Factors; Treatment Outcome; Ultrasonography; Venous Thrombosis

The benefit-risk ratio of extended fondaparinux therapy has not been assessed in patients undergoing major lower limb joint arthroplasty. Few data on the concomitant use of fondaparinux and continuous neuraxial or deep peripheral nerve blockade are available. We performed a prospective intervention study in patients undergoing major orthopedic surgery primarily designed to assess the efficacy of fondaparinux when drug administration was withheld for 48 h to permit removal of a neuraxial or deep peripheral nerve catheter. The safety and efficacy of extended fondaparinux therapy for the prevention of venous thromboembolism were also evaluated.. Patients received a daily subcutaneous injection of 2.5 mg fondaparinux for 3 to 5 wk postoperatively. In patients with a neuraxial or deep peripheral nerve catheter, the catheter was removed 36 h after the last fondaparinux dose. The next fondaparinux dose was administered 12 h after catheter removal. The primary end points were symptomatic venous thromboembolism and major bleeding up to 4-6 wk after surgery.. We recruited 5704 patients. A neuraxial or deep peripheral nerve catheter was inserted in 1553 (27%) patients and 78 (1.4%) patients, respectively. The rate of venous thromboembolism was 1.0% (54 of 5387). There was no difference between patients without (1.1%) or with (0.8%) a catheter (the upper limit of the 95% confidence interval of the odds ratio, 1.49, being below the predetermined noninferiority margin of 1.75). The incidence of major bleeding was 0.8% (42 of 5382). No neuraxial or perineural hematoma was reported.. Once-daily subcutaneous injection of 2.5 mg fondaparinux given for 3 to 5 wk was effective and safe for prevention of venous thromboembolism after major orthopedic surgery. Temporary discontinuation of fondaparinux for 48 h permitted safe removal of a neuraxial or deep peripheral nerve catheter without decreasing thromboprophylatic efficacy.

Topics: Aged; Catheterization; Female; Fondaparinux; Humans; Internationality; Lower Extremity; Male; Middle Aged; Orthopedic Procedures; Peripheral Nerves; Polysaccharides; Postoperative Complications; Prospective Studies; Thrombolytic Therapy; Time Factors; Venous Thrombosis

Fondaparinux, a new synthetic pentasaccharide has proven to be a more potent thromboprophylactic drug compared to enoxaparin after major orthopaedic surgery. However, the safety of fondaparinux regarding wound healing has not yet been investigated.. We performed a single-centre prospective clinical trial, in which patients undergoing total knee arthroplasty or revision of at least one of the components of a previous knee arthroplasty were randomly assigned to thromboprophylaxis with fondaparinux or enoxaparin. The trial included 109 patients and wound discharge was compared. Secondary outcome measures were the amount of blood in the suction drain, postoperative transfusion rate, change in haemoglobin levels, haematocrit, intervention rate, time to regain flexion and rate of symptomatic thromboembolic events.. 55 patients were treated with fondaparinux and 54 with enoxaparin. Base-line characteristics were similar. In both groups wound dressings remained dry after five (5.17+/-2.5 and 5.19+/-3) days postoperatively. There were no significant differences in any of our outcome measures.. We did not find any significant difference in wound healing with fondaparinux after major knee surgery. Post hoc analyses suggested the study should have had a sample size of 155 in each group. We believe this trial should be used as a pilot study for further investigations concerning the safety of thromboprophylaxis.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Female; Follow-Up Studies; Fondaparinux; Humans; Joint Diseases; Male; Middle Aged; Polysaccharides; Prospective Studies; Reoperation; Venous Thrombosis; Wound Healing

To determine the efficacy and safety of the anticoagulant fondaparinux in older acute medical inpatients at moderate to high risk of venous thromboembolism.. Double blind randomised placebo controlled trial.. 35 centres in eight countries.. 849 medical patients aged 60 or more admitted to hospital for congestive heart failure, acute respiratory illness in the presence of chronic lung disease, or acute infectious or inflammatory disease and expected to remain in bed for at least four days.. 2.5 mg fondaparinux or placebo subcutaneously once daily for six to 14 days.. The primary efficacy outcome was venous thromboembolism detected by routine bilateral venography along with symptomatic venous thromboembolism up to day 15. Secondary outcomes were bleeding and death. Patients were followed up at one month.. 425 patients in the fondaparinux group and 414 patients in the placebo group were evaluable for safety analysis (10 were not treated). 644 patients (75.9%) were available for the primary efficacy analysis. Venous thrombembolism was detected in 5.6% (18/321) of patients treated with fondaparinux and 10.5% (34/323) of patients given placebo, a relative risk reduction of 46.7% (95% confidence interval 7.7% to 69.3%). Symptomatic venous thromboembolism occurred in five patients in the placebo group and none in the fondaparinux group (P = 0.029). Major bleeding occurred in one patient (0.2%) in each group. At the end of follow-up, 14 patients in the fondaparinux group (3.3%) and 25 in the placebo group (6.0%) had died.. Fondaparinux is effective in the prevention of asymptomatic and symptomatic venous thromboembolic events in older acute medical patients. The frequency of major bleeding was similar for both fondaparinux and placebo treated patients.

Topics: Acute Disease; Aged; Anticoagulants; Bed Rest; Chronic Disease; Disease-Free Survival; Double-Blind Method; Female; Follow-Up Studies; Fondaparinux; Hemorrhage; Hospitalization; Humans; Male; Middle Aged; Polysaccharides; Thromboembolism; Treatment Outcome; Venous Thrombosis

Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4) bound to heparin. Immunogenicity of heparins differs in that unfractionated heparin (UFH) induces more anti-PF4/heparin antibodies than low-molecular-weight heparin (LMWH) and UFH also causes more HIT. Fondaparinux, a synthetic anticoagulant modeled after the antithrombin-binding pentasaccharide, is believed to be nonimmunogenic. We tested 2726 patients for anti-PF4/heparin antibodies after they were randomized to receive antithrombotic prophylaxis with fondaparinux or LMWH (enoxaparin) following hip or knee surgery. We also evaluated in vitro cross-reactivity of the IgG antibodies generated against PF4 in the presence of UFH, LMWH, danaparoid, or fondaparinux. We found that anti-PF4/heparin antibodies were generated at similar frequencies in patients treated with fondaparinux or enoxaparin. Although antibodies reacted equally well in vitro against PF4/UFH and PF4/LMWH, and sometimes weakly against PF4/danaparoid, none reacted against PF4/fondaparinux, including even those sera obtained from patients who formed antibodies during fondaparinux treatment. At high concentrations, however, fondaparinux inhibited binding of HIT antibodies to PF4/polysaccharide, indicating that PF4/fondaparinux interactions occur. No patient developed HIT. We conclude that despite similar immunogenicity of fondaparinux and LMWH, PF4/fondaparinux, but not PF4/LMWH, is recognized poorly by the antibodies generated, suggesting that the risk of HIT with fondaparinux likely is very low.

Topics: Anticoagulants; Cross Reactions; Double-Blind Method; Enoxaparin; Fondaparinux; Hip; Humans; Immunoenzyme Techniques; Immunoglobulin G; Knee; Orthopedic Procedures; Platelet Factor 4; Polysaccharides; Thrombocytopenia; Venous Thrombosis

The aim of this study was to assess whether the synthetic factor Xa inhibitor fondaparinux reduced the risk of venous thromboembolism more efficiently than the low molecular weight heparin dalteparin in patients undergoing major abdominal surgery.. In a double-blind double-dummy randomized study, patients scheduled for major abdominal surgery under general anaesthesia received once-daily subcutaneous injections of fondaparinux 2.5 mg or dalteparin 5000 units for 5-9 days. Fondaparinux was started 6 h after surgery. The first two doses of dalteparin, 2500 units each, were given 2 h before surgery and 12 h after the preoperative administration. The primary outcome measure was a composite of deep vein thrombosis detected by bilateral venography and symptomatic, confirmed deep vein thrombosis or pulmonary embolism up until day 10. The main safety outcome measure was major bleeding during treatment.. Among 2048 patients evaluable for efficacy, the rate of venous thromboembolism was 4.6 per cent (47 of 1027) with fondaparinux compared with 6.1 per cent (62 of 1021) with dalteparin, a relative risk reduction of 24.6 (95 per cent confidence interval -9.0 to 47.9) per cent (P = 0.144), which met the predetermined criterion for non-inferiority of fondaparinux. Major bleeding was observed in 49 (3.4 per cent) of 1433 patients given fondaparinux and 34 (2.4 per cent) of 1425 given dalteparin (P = 0.122).. Postoperative fondaparinux was at least as effective as perioperative dalteparin in patients undergoing high-risk abdominal surgery.

Topics: Abdomen; Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Anticoagulants; Double-Blind Method; Female; Fondaparinux; Humans; Male; Middle Aged; Polysaccharides; Postoperative Complications; Risk Factors; Thromboembolism; Treatment Outcome; Venous Thrombosis

The current standard initial therapies for deep venous thrombosis are low-molecular-weight heparin and unfractionated heparin. In a dose-ranging study of patients with symptomatic deep venous thrombosis, fondaparinux had efficacy and a safety profile similar to those of low-molecular-weight heparin (dalteparin).. To evaluate whether fondaparinux has efficacy and safety similar to those of enoxaparin in patients with deep venous thrombosis.. Randomized, double-blind study.. 154 centers worldwide.. 2205 patients with acute symptomatic deep venous thrombosis.. Fondaparinux, 7.5 mg (5.0 mg in patients weighing <50 kg and 10.0 mg in patients weighing >100 kg) subcutaneously once daily, or enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an international normalized ratio greater than 2.0.. The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolic complications. The main safety outcomes were major bleeding during initial treatment and death. An independent, blinded committee adjudicated all outcomes.. 43 (3.9%) of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 (4.1%) of 1107 patients randomly assigned to enoxaparin (absolute difference, -0.15 percentage point [95% CI, -1.8 to 1.5 percentage points]). Major bleeding occurred in 1.1% of patients receiving fondaparinux and 1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and 3.0%, respectively.. Follow-up was incomplete in 0.4% of fondaparinux-treated patients and 1.0% of enoxaparin-treated patients.. Once-daily subcutaneous fondaparinux was at least as effective (not inferior) and safe as twice-daily, body weight-adjusted enoxaparin in the initial treatment of patients with symptomatic deep venous thrombosis.

Topics: Aged; Body Weight; Cause of Death; Double-Blind Method; Drug Administration Schedule; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Kidney; Male; Middle Aged; Polysaccharides; Recurrence; Treatment Outcome; Venous Thrombosis; Vitamin K

To assess the relevance of various efficacy end points established for thromboprophylaxis trials, we compared the results of the fondaparinux phase III program in major orthopedic surgery using the original primary efficacy end point with those obtained when the efficacy end points recently suggested by the American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy and the European Committee for Proprietary Medicinal Products (CPMP) were used.. Fondaparinux was compared with enoxaparin in four multicenter, randomized, double-blind trials of major orthopedic surgery. The original primary efficacy end point consisted of a composite of deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or pulmonary embolism up to day 11. The efficacy end point established by the ACCP Consensus Conference on Antithrombotic Therapy comprises any proximal deep-vein thrombosis, symptomatic proven deep-vein thrombosis or pulmonary embolism, or fatal pulmonary embolism, and that established by the European CPMP comprises any proximal deep-vein thrombosis, symptomatic proven pulmonary embolism, or death from any cause.. Patients were randomized to receive either subcutaneous fondaparinux (2.5 mg once daily) starting postoperatively or approved enoxaparin regimens.. Using the original end point of the fondaparinux studies, the incidence of venous thromboembolism was 13.7% (371 of 2,703 patients) in the enoxaparin group compared with 6.8% (182 of 2,682 patients) in the fondaparinux group, with a common odds reduction of 55.2% (p = 10(-17); 95% confidence interval, 45.8% to 63.1%) in favor of fondaparinux. The respective incidences of efficacy end points with enoxaparin and fondaparinux were 3.3% and 1.7%, respectively, according to the ACCP definition, and 3.9% and 2.1%, respectively, according to the CPMP definition. The common odds reduction in favor of fondaparinux was 49.6% (p < 0.001) and 48.0% (p < 0.001), respectively.. Fondaparinux was consistently more effective than enoxaparin in preventing venous thromboembolism in patients undergoing major orthopedic surgery, irrespective of the established composite outcomes used.

Topics: Adolescent; Double-Blind Method; Endpoint Determination; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Humans; Injections, Subcutaneous; Orthopedic Procedures; Polysaccharides; Venous Thrombosis

Fondaparinux efficacy for thromboprophylaxis was evaluated in predefined high-risk hip fracture patients. Patients received fondaparinux 2.5 mg for 7 days following surgery; 656 patients were randomized double blind to receive placebo or continue fondaparinux regimen for 21 additional days. Primary efficacy was venous thromboembolism (VTE) based on bilateral venography during the double-blind period. Total VTE was 1.4% (3 of 208 patients) for extended prophylaxis and 35% (77 of 220 patients) for short-term prophylaxis (P = 0.001), relative risk reduction (RRR) of 96%. Major bleeding occurred in 2% (8 of 327 patients) with extended prophylaxis and in 0.6% (2 of 329 patients) with short-term prophylaxis (P =.063). Risk of VTE was continued following short course fondaparinux in hip fracture patients, but was significantly reduced by extending prophylaxis, without significant risk of major bleeding.

Topics: Aged; Anticoagulants; Double-Blind Method; Female; Fondaparinux; Hip Fractures; Humans; Logistic Models; Male; Middle Aged; Polysaccharides; Treatment Outcome; Venous Thrombosis

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

Topics: Factor Xa Inhibitors; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Thromboembolism; Venous Thrombosis

A worldwide phase III program, consisting of four randomized, double-blind trials in patients undergoing surgery for hip fracture, in elective hip replacement surgery patients and in elective major knee surgery patients, was conducted to compare the benefit-to-risk ratio of a subcutaneous 2.5-mg once-daily regimen of fondaparinux, a synthetic selective factor Xa inhibitor, starting postoperatively with enoxaparin in preventing venous thromboembolism. The overall incidence of venous thromboembolism up to day 11 was reduced from 13.7% in the enoxaparin group to 6.8% in the fondaparinux group with a common odds reduction of 55.2% in favor of fondaparinux (95% confidence interval: 45.8-63.1%, p = 10(-17)). This superior efficacy of fondaparinux was also demonstrated for proximal deep vein thrombosis with a reduction of 57.4%. The overall incidence of clinically relevant bleeding was low and did not differ between the two groups. The benefit of fondaparinux was consistent across all types of surgery and all subgroups.

Topics: Adolescent; Adult; Aged; Anticoagulants; Enoxaparin; Fondaparinux; Humans; Middle Aged; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Safety; Treatment Outcome; Venous Thrombosis

Despite use of thromboprophylaxis, elective hip-replacement surgery carries a high risk of venous thromboembolic complications. We aimed to assess the ability of the pentasaccharide fondaparinux, the first of a new class of synthetic antithrombotic agents, to further reduce this risk.. In a double-blind study, we randomly assigned 2309 consecutive patients aged 18 years or older who were undergoing elective hip-replacement surgery to once daily, subcutaneous injections of either 2.5 mg fondaparinux, starting postoperatively, or 40 mg enoxaparin, starting preoperatively. The primary efficacy outcome was venous thromboembolism up to day 11, 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 bleeding and death. The duration of follow-up was 6 weeks. Analysis was per protocol.. We assessed the primary efficacy outcome in 1827 (79%) of 2309 patients. By day 11, venous thromboembolisms were recorded in 37 (4%) of 908 patients assigned to fondaparinux and in 85 (9%) of 919 assigned to enoxaparin (difference -5.2% [95% CI -8.1 to -2.7], p<0.0001). The relative reduction in risk was 55.9% (95% CI 33.1-72.8). The two groups did not differ in frequency of death or clinically relevant bleeding.. Drugs that act through specific inhibition of factor Xa, such as fondaparinux, could be more effective than low molecular weight heparins in prevention of venous thromboembolism in patients undergoing hip-replacement surgery.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Double-Blind Method; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hospital Mortality; Humans; Male; Middle Aged; Polysaccharides; Postoperative Care; Postoperative Complications; Preoperative Care; Venous Thrombosis

Elective hip-replacement surgery carries significant risk of venous thromboembolism, despite use of thromboprophylaxis. We aimed to see whether the pentasaccharide fondaparinux, the first drug of a new class of synthetic antithrombotic agents, could reduce this risk to a greater extent than other available treatments.. In a double-blind study, we randomly assigned 2275 consecutive patients aged 18 years or older who were undergoing elective hip-replacement surgery to receive postoperative subcutaneous injections of either 2.5 mg fondaparinux once daily or 30 mg enoxaparin twice daily. The primary efficacy outcome was venous thromboembolism to day 11. The main safety outcomes were bleeding and death. Patients were followed up for 6 weeks.. We assessed venous thromboembolism to day 11 in 1584 (70%) of 2275 patients. By day 11, venous thromboembolisms were recorded in 48 (6%) of 787 patients on fondaparinux and in 66 (8%) of 797 patients on enoxaparin. The relative reduction in risk was 26.3% (95% CI -10.8 to 52.8, p=0.099). The two groups did not differ in the number of patients who died or in the number who had clinically relevant bleeding.. In patients undergoing elective hip-replacement surgery, 2.5 mg fondaparinux once daily was not significantly more effective than 30 mg enoxaparin twice daily in reducing risk of venous thromboembolism. However, the lower risk recorded with fondaparinux than enoxaparin was clinically important, with no increase in clinically relevant bleeding.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Double-Blind Method; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Humans; Male; Middle Aged; Polysaccharides; Postoperative Care; Postoperative Complications; Preoperative Care; Venous Thrombosis

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

Fondaparinux is a synthetic anticoagulant that inhibits thrombosis by suppressing factor Xa. The efficacy of fondaparinux for orthopedic surgeries has been revealed by several foreign studies; however, relevant evidence in Chinese patients is lacking. This study intended to investigate the occurrence rate and risk factors of in-hospital venous thromboembolism (VTE), major bleeding, and death in patients receiving fondaparinux after orthopedic surgery or trauma surgery.. Totally, 1258 patients who received fondaparinux after orthopedic surgery or trauma surgery were retrospectively enrolled. Meanwhile, in-hospital VTE, major bleeding, and death were obtained for assessment. Besides, adverse events were recorded.. The occurrence rates of in-hospital VTE, major bleeding, and death were 2.5%, 21.8%, and 0.0%, respectively. The multivariate logistic regression analysis revealed that only age (> 60 years vs. ≤ 60 years) (odd ratios (OR) = 3.380, P = 0.013) was independently correlated with increased risk of in-hospital VTE. Additionally, osteoarthritis diagnosis (OR = 3.826, P < 0.001), femoral head necrosis diagnosis (OR = 1.809, P = 0.034), hip replacement (vs. internal fracture fixation) (OR = 2.199, P = 0.007), knee replacement (vs. internal fracture fixation) (OR = 2.781, P = 0.002), and serum creatinine (abnormal vs. normal) (OR = 1.677, P = 0.012) were independently linked to a higher risk of in-hospital major bleeding. Moreover, the common adverse events included pain (56.6%), wound bleeding (23.0%), increased drainage (5.2%), etc. CONCLUSION: Fondaparinux realizes low occurrence rates of in-hospital VTE and major bleeding with tolerable adverse events in patients receiving orthopedic surgery or trauma surgery.

Topics: Anticoagulants; Fondaparinux; Fracture Fixation, Internal; Hemorrhage; Humans; Middle Aged; Orthopedic Procedures; Polysaccharides; Retrospective Studies; Risk Factors; Venous Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Cardiology; Fondaparinux; Humans; Thrombosis; 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

A large German registry on superficial vein thrombosis (SVT) documents that risk profiles, clinical presentation and treatment patterns are highly variable in patients with SVT, including a large variation in anticoagulation treatment modalities, intensities and durations. Inspite of a high percentage of initial anticoagulation there is a substantial risk of subsequent venous thromboembolism (VTE), recurrences or extension after three months. Inspite of current guideline recommendations, one third of the patients receives heparins, oral anticoagulants or no anticoagulation at all. At initial presentation about one quarter of the patients with SVT have a concomitant, frequently asymptomatic VTE. Risk factors for this complication include prior hospitalization, immobilization, prior VTE, autoimmune disorders, higher age, cancer and SVT occurring in a non-varicose veins or SVT-extension into the perforator veins. These risk factors are also associated with thromboembolic complications during follow-up.. Based on a large placebo-controlled trial with clinical endpoints (The CALISTO-Study), guidelines recommend Fondaparinux 2.5 mg once daily administered over 4 to 6 weeks. Alternatively, an intermediate dose of low molecular weight heparin can be considered. In high-risk patients, rivaroxaban 10 mg once daily was noninferior compared to Fondaparinux. A rebound of VTE recurrences was observed in both study arms after treatment had been discontinued after 45 days. Further studies are required to determine whether treatment needs to be extended beyond 45 days in high-risk patients.. Eine deutsche Registerstudie zeigt, dass Risikoprofile, klinisches Bild und Behandlungsmuster bei oberflächlicher Venenthrombose (OVT) sehr heterogen sind. Ebenso variieren Dosierung und Therapiedauer der Antikoagulation (AK) erheblich. Trotz initialer AK besteht nach 3 Monaten ein beachtliches Risiko für venöse Thromboembolien (VTE), Rezidive oder Ausdehnung. Im Gegensatz zu aktuellen Leitlinienempfehlungen erhielt ein Drittel der Patienten entweder Heparine, orale Antikoagulanzien oder gar kein Antikoagulans. Eine gleichzeitige, oft asymptomatische tiefe Venenthrombose (TVT) findet sich gehäuft nach Hospitalisierung oder Immobilisation, vorausgegangener VTE, bei Autoimmunerkrankungen, höherem Alter, Malignom und bei OVT in einer nichtvarikösen Vene oder bei Ausdehnung in eine Perforansvene. Dies sind häufig auch Risikofaktoren für thromboembolische Komplikationen im Verlauf.. Aufgrund einer großen Placebo-kontrollierten Studie mit klinischen Endpunkten ist Fondaparinux 1-mal 2,5 mg über 4–6 Wochen die in den Leitlinien empfohlene Therapie. Auch eine intermediäre Dosis von niedermolekularem Heparin (NMH) kann erwogen werden. Bei Hochrisikopatienten war 1-mal 10 mg Rivaroxaban gegenüber Fondaparinux nicht unterlegen. Ob bei hohem Risiko eine 45-tägige Therapie ausreicht, muss weiter untersucht werden.

Topics: Anticoagulants; Fondaparinux; Germany; Heparin, Low-Molecular-Weight; Humans; Risk Factors; Venous Thrombosis

The aim of this study was to assess the incidence of deep vein thrombosis (DVT) of the lower limbs, using serial compression ultrasound (CUS) surveillance, in acutely ill patients with COVID-19 pneumonia admitted to a non-ICU setting.. Multicenter, prospective study of patients with COVID-19 pneumonia admitted to Internal Medicine units. All patients were screened for DVT of the lower limbs with serial CUS. Anticoagulation was defined as: low dose (enoxaparin 20-40 mg/day or fondaparinux 1.5-2.5 mg/day); intermediate dose (enoxaparin 60-80 mg/day); high dose (enoxaparin 120-160 mg or fondaparinux 5-10 mg/day or oral anticoagulation). The primary end-point of the study was the diagnosis of DVT by CUS.. Over a two-month period, 227 consecutive patients with moderate-severe COVID-19 pneumonia were enrolled. The incidence of DVT was 13.7% (6.2% proximal, 7.5% distal), mostly asymptomatic. All patients received anticoagulation (enoxaparin 95.6%) at the following doses: low 57.3%, intermediate 22.9%, high 19.8%. Patients with and without DVT had similar characteristics, and no difference in anticoagulant regimen was observed. DVT patients were older (mean 77±9.6 vs 71±13.1 years; p = 0.042) and had higher peak D-dimer levels (5403 vs 1723 ng/mL; p = 0.004). At ROC analysis peak D-dimer level >2000 ng/mL (AUC 0.703; 95% CI 0.572-0.834; p = 0.004) was the most accurate cut-off value able to predict DVT (RR 3.74; 95%CI 1.27-10, p = 0.016).. The incidence of DVT in acutely ill patients with COVID-19 pneumonia is relevant. A surveillance protocol by serial CUS of the lower limbs is useful to timely identify DVT that would go otherwise largely undetected.

Topics: Aged; Aged, 80 and over; Anticoagulants; COVID-19; Enoxaparin; Female; Fondaparinux; Humans; Incidence; Lower Extremity; Male; Middle Aged; Ultrasonography; Venous Thrombosis

To describe the successful recovery from multiple and life-threatening venous thrombosis after ChAdOx1 nCoV-19 vaccination.. Case report.. University Hospital.. Few days after the first dose of the ChAdOx1 nCoV-19 vaccine, a 21-year-old woman experienced massive thrombosis in the deep and superficial cerebral veins together with seizures, neurologic focal deficit, and thrombocytopenia. In the neurointensive care unit, her condition worsened despite early decompressive craniectomy. She developed bilateral segmental pulmonary embolism, left hepatic, and left external iliac venous thrombosis.. Argatroban (0.5-2.2 µg/kg/min) and high-dose IV immunoglobulin (1 g/kg/d for 2 consecutive days) were initiated on day 6 after admission. With these therapies, there was a gradual resolution of multiple sites of venous thrombosis, and platelet count returned to normal. The patient left the ICU with full consciousness, expressive aphasia, and right hemiparesis.. This case of vaccine-induced immune thrombotic thrombocytopenia shows that a good outcome can be obtained even with multiple and life-threatening venous thrombotic lesions. Argatroban and high-dose IV immunoglobulin along with management of severe cerebral venous thrombosis played a major role in this epilogue.

Topics: Antithrombins; Arginine; Cerebral Veins; ChAdOx1 nCoV-19; COVID-19 Vaccines; Drug Therapy, Combination; Female; Fondaparinux; Humans; Immunoglobulins, Intravenous; Pipecolic Acids; Sulfonamides; Thrombocytopenia; Tomography, X-Ray Computed; Venous Thrombosis; Young Adult

Portal vein thrombosis is the most common thrombotic complication in cirrhosis. About 60% of anticoagulated patients can achieve recanalization. Despite fondaparinux (FPX) theoretical advantages, data are lacking about safety and efficacy for treatment of portal vein thrombosis in cirrhosis.. Cirrhotic patients with portal vein thrombosis treated with FPX or low-molecular-weight heparin (LMWH) were retrospectively included. The extension of thrombosis at baseline and its evolution during anticoagulant treatment were evaluated. Patients were treated with LMWH or FPX at therapeutic dosage and reduction was considered in selected cases.. There were 124 patients included. Main portal vein branch, splenic, and superior mesenteric veins were involved in 84%, 13%, and 36% of cases, respectively. Forty-one patients (33%) were treated with FPX and 83 (67%) with LMWH. The probability of resolution of thrombosis at 36 months was significantly higher in patients treated with FPX than in those treated with LMWH (77% vs 51%; P = .001), particularly when prescribed at reduced dose. With multivariate analysis, the treatment with FPX (hazard ratio 2.38; P = .002) and use of a full dose (hazard ratio 1.78; P = .035) were independent predictors of portal vein full recanalization. Bleeding rate was higher in patients treated with FPX than in those treated with LMWH (27% vs 13%; P = .06).. FPX appears to be more effective than LMWH in the treatment of portal vein thrombosis when used at reduced dose, also in complete thrombosis. FPX should be considered among possible treatments for portal vein thrombosis in cirrhosis.

Topics: Anticoagulants; Factor Xa Inhibitors; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Retrospective Studies; Venous Thrombosis

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

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

A remarkably high incidence of venous thromboembolism (VTE) has been reported among critically ill patients with COVID-19 assisted in the intensive care unit (ICU). However, VTE burden among non-ICU patients hospitalized for COVID-19 that receive guideline-recommended thromboprophylaxis is unknown.. To determine the incidence of VTE among non-ICU patients hospitalized for COVID-19 that receive pharmacological thromboprophylaxis.. We performed a systematic screening for the diagnosis of deep vein thrombosis (DVT) by lower limb vein compression ultrasonography (CUS) in consecutive non-ICU patients hospitalized for COVID-19, independent of the presence of signs or symptoms of DVT. All patients were receiving pharmacological thromboprophylaxis with either enoxaparin or fondaparinux.. The population that we screened consisted of 84 consecutive patients, with a mean age of 67.6 ± 13.5 years and a mean Padua Prediction Score of 5.1 ± 1.6. Seventy-two patients (85.7%) had respiratory insufficiency, required oxygen supplementation, and had reduced mobility or were bedridden. In this cohort, we found 10 cases of DVT, with an incidence of 11.9% (95% confidence interval [CI] 4.98-18.82). Of these, 2 were proximal DVT (incidence rate 2.4%, 95% CI -0.87-5.67) and 8 were distal DVT (incidence rate 9.5%, 95% CI 3.23-5.77). Significant differences between subjects with and without DVT were D-dimer > 3000 µg/L (P < .05), current or previous cancer (P < .05), and need of high flow nasal oxygen therapy and/or non-invasive ventilation (P < .01).. DVT may occur among non-ICU patients hospitalized for COVID-19, despite guideline-recommended thromboprophylaxis.

Topics: Aged; Aged, 80 and over; COVID-19; Enoxaparin; Female; Fondaparinux; Guidelines as Topic; Hospitalization; Humans; Incidence; Lower Extremity; Male; Middle Aged; Ultrasonography; Venous Thromboembolism; Venous Thrombosis

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

Topics: Body Contouring; Fondaparinux; Humans; Postoperative Period; Venous Thromboembolism; Venous Thrombosis

Portal vein thrombosis (PVT) is a frequent complication of cirrhosis. Benefit, safety, and duration of anticoagulant treatment in this setting are controversial issues. The aim of this study was to analyze the course of PVT in a large cohort of cirrhotic patients undergoing or not anticoagulation therapy.. The data of 182 patients who presented between January 2008 and March 2016 with cirrhosis and PVT with at least 3 months of follow-up after the first PVT detection were analyzed. Eighty-one patients received anticoagulants and 101 were untreated per physician discretion.. The extension of the thrombosis decreased by >50% in 46 (56.8%, with complete recanalization in 31/46) patients under anticoagulation and in 26 (25.7%) untreated patients. Of the 46 patients who underwent recanalization, 17 (36%) suffered recurrent thrombosis after stopping anticoagulation therapy. Kaplan-Meier analysis showed a higher survival rate in the treated group (p = 0.010). At multivariate analysis, anticoagulation was an independent factor associated with longer survival (HR:0.30, CI:0.10-0.91, p = 0.014). The Child-Turcotte-Pugh classes B/C negatively influenced survival (hazard ratio, (HR):3.09, confidence interval (CI):1.14-8.36, p = 0.027 for Child-Turcotte-Pugh B and HR:9.27, CI:2.67-32.23, p < 0.001 for Child-Turcotte-Pugh C). Bleeding complications occurred in 22 (21.8%) untreated and 16 (19.7%) treated patients, but in only four cases was it judged to be related to the anticoagulant treatment. No death was reported as a consequence of the bleeding events.. Anticoagulant treatment is a safe and effective treatment leading to partial or complete recanalization of the portal venous system in 56.8% of cases, improving the survival of patients with cirrhosis and PVT. Discontinuation of the therapy is associated with a high rate of PVT recurrence.

Topics: Aged; Anticoagulants; Esophageal and Gastric Varices; Female; Fondaparinux; Gastrointestinal Hemorrhage; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Venous Thrombosis

Many strategies for venous thromboembolism (VTE) prophylaxis following hip and knee arthroplasty exist, with extensive controversy regarding the optimum strategy to minimize risk of VTE and bleeding complications. Data from the American Board of Orthopedic Surgery Part II (oral) Examination case list database was analyzed to determine efficacy, complication rates, and prescribing patterns for different prophylactic strategies.. The American Board of Orthopedic Surgery case database was queried utilizing Current Procedural Terminology codes 27447 and 27130 for primary total knee and hip arthroplasty, respectively. Geographic region, patient age, gender, deep vein thrombosis prophylaxis strategy, and complications were obtained. Less aggressive prophylaxis patterns were considered if only aspirin and/or sequential compression devises were utilized. More aggressive VTE prophylaxis patterns were considered if any of low-molecular-weight heparin (enoxaparin), warfarin, rivaroxaban, fondaparinux, or other strategies was used.. In total, 22,072 cases of primary joint arthroplasty were analyzed from 2014 to 2016. The national rate of less aggressive VTE prophylaxis strategies was 45.4%, while more aggressive strategies were used in 54.6% of patients. Significant regional differences in prophylactic strategy patterns exist between the 6 regions. The predominant less aggressive prophylaxis pattern was aspirin with sequential compression devises at 84.8% with 14.8% receiving aspirin alone. Use of less aggressive prophylaxis strategy was significantly associated with patients having no complications (95.5% vs 93.0%). Use of more aggressive prophylaxis patterns was associated with higher likelihood of mild thrombotic (0.9% vs 0.2%), mild bleeding (1.3% vs 0.4%), moderate thrombotic (1.2% vs 0.4%), moderate bleeding (2.7% vs 2.1%), severe thrombotic (0.1% vs 0.0%), severe bleeding events (1.2% vs 0.9%), infections (1.9% vs 1.3%), and death within 90 days (0.7% vs 0.3%). Similar results were found in subgroup analysis of total hip and knee arthroplasty patients.. It was not possible to ascertain the individual rationale for use of more aggressive VTE prophylaxis strategies; however, more aggressive strategies were associated with higher rates of bleeding and thrombotic complications. Less aggressive strategies were not associated with a higher rate of thrombosis.. Therapeutic Level III.. All views expressed in the study are the sole views of the authors and do not represent the views of the American Board of Orthopedic Surgery.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Databases, Factual; Enoxaparin; Female; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Orthopedic Procedures; Orthopedics; Practice Patterns, Physicians'; Risk Factors; Rivaroxaban; United States; Venous Thromboembolism; Venous Thrombosis; Warfarin

We present important laboratory testing and clinical management strategies used to safely discharge home a 69-year old woman with heparin-induced thrombocytopenia (HIT) from the hospital. She was admitted for a coronary artery bypass graft procedure for which she was anticoagulated with heparin. Shortly after the procedure she developed thrombocytopenia and was diagnosed with HIT using the 4Ts scoring system, a latex-enhanced immunoassay (LEI) screen and confirmatory serotonin release assay. Her anticoagulation was switched from heparin to argatroban, and response to treatment was monitored in the laboratory using LEI. Unfortunately, she also received platelet transfusions and subsequently developed multifocal deep vein thrombosis with worsening platelet counts with nadir less than 10 x 10^3/μL. After five therapeutic plasma exchange procedures we noted an improvement in platelet counts, which plateaued into the 50s x 10^3/μL. Furthermore, the LEI remained positive. At this juncture we decided to transition from argatroban to fondaparinux so that she could leave the hospital in stable condition. Upon follow-up with hematology she exhibited no worsening clinical signs or symptoms of disease, and platelet counts markedly improved to within normal limits of detection. In this report we examine the utility of LEI in monitoring patients with HIT, therapeutic plasma exchange in the management of severe HIT (with thrombosis), and the use of subcutaneous fondaparinux in managing HIT in the outpatient setting.

Topics: Aged; Arginine; Coronary Artery Bypass; Female; Fondaparinux; Heparin; Humans; Pipecolic Acids; Platelet Count; Platelet Transfusion; Sulfonamides; Thrombocytopenia; 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

Inferior vena cava (IVC) thrombosis is an under-recognized entity that is associated with a mortality rate approaching twice that of lower extremity deep venous thrombosis (DVT). Thrombolytic therapy not only results in greater lysis, but also results in higher complication rates than anticoagulation alone. Catheter-directed thrombolysis (CDT), which is effective in accomplishing local resolution whilst reducing bleeding complications, has been established as an alternative treatment for patients with extensive DVT.. We report the case of a 70-year-old man who was admitted due to warmness, pain, and swelling in his left leg and a feeling of gait disturbance.. Contrast-enhanced computed tomography and venous ultrasonography revealed a pulmonary embolism and extensive DVT spreading to the IVC.. First, the patient was treated with fondaparinux. Since this was inadequate, he underwent CDT using a Fountain infusion catheter. Then, CDT was switched to direct oral anticoagulant (DOAC) treatment.. Both CDT and subsequent DOAC treatments dramatically improved the DVT. His subjective symptoms have disappeared, and no recurrence of thrombosis has been identified.. The present case showed the therapeutic effect of CDT, which preceded DOAC treatment, on an extensive DVT.

Topics: Aged; Anticoagulants; Catheterization, Peripheral; Fondaparinux; Hemorrhage; Humans; Male; Polysaccharides; Thrombolytic Therapy; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Interventional; Vena Cava, Inferior; Venous Thrombosis

Patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) are at high risk of deep vein thrombosis (DVT) postoperatively, necessitating the use of prophylaxis medications. This investigation used a large claims database to evaluate trends in postoperative DVT prophylaxis and rates of DVT within 6 months after THA or TKA.. Truven Health MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases were reviewed from 2004 to 2013 for patients who underwent THA or TKA. Data were collected on patient age, sex, Charlson Comorbidity Index, and hypercoagulability diagnoses. Postoperative medication claims were reviewed for prescribed aspirin, warfarin, enoxaparin, fondaparinux, rivaroxaban, and dabigatran.. A total of 369,483 patients were included in the analysis, of which 239,949 patients had prescription medication claims. Warfarin was the most commonly prescribed anticoagulant. Patients with a hypercoagulable diagnosis had markedly more DVTs within 6 months after THA or TKA. More patients with a hypercoagulable diagnosis were treated with warfarin or lovenox than other types of anticoagulants. A multivariate regression analysis was performed, showing that patients prescribed aspirin, fondaparinux, and rivaroxaban were markedly less likely than those prescribed warfarin or enoxaparin to have a DVT within 6 months after THA or TKA.. After THA and TKA, warfarin is the most commonly prescribed prophylaxis. Patients with hypercoagulability diagnoses are at a higher risk of postoperative DVT. The likelihood of DVT within 6 months of THA and TKA was markedly higher in patients treated with warfarin and lovenox and markedly lower in those treated with aspirin, fondaparinux, and rivaroxaban.. Level III.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Clinical Decision-Making; Dabigatran; Databases, Factual; Enoxaparin; Female; Fondaparinux; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thrombosis; Warfarin

A 34-year-old primigravida who had undergone thrombectomy for deep venous thrombosis (DVT) in her leg and exhibited low protein S activity, indicating predisposition to thrombosis, developed DVT of the leg. No pulmonary embolism was detected. After anticoagulant therapy with unfractionated heparin was discontinued because of liver dysfunction, danaparoid treatment was administered in hospital. The patient had a normal delivery after 39 weeks' gestation with no recurrence of thrombosis. During her second pregnancy four years later, she gave herself fondaparinux injections. She delivered normally after 38 weeks' gestation without experiencing DVT. Fondaparinux may be a useful anticoagulant for heparin-intolerant pregnant women.

Topics: Adult; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Polysaccharides; Pregnancy; Pregnancy Complications, Cardiovascular; Venous Thrombosis

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

Pharmacologic options for venous thromboembolism (VTE) prophylaxis are often limited in critically ill patients due to thrombocytopenia and multisystem organ dysfunction. Fondaparinux offers potential advantages in the critically ill; however, it is currently contraindicated in severe renal dysfunction (SRD). We evaluated anti-factor Xa levels in critically ill patients with SRD who were receiving an extended interval dosing regimen of fondaparinux for VTE prophylaxis.. A prospective, single-arm, interventional study was conducted at two academic hospitals of the Detroit Medical Center. Eligible patients were in the intensive care unit, had an estimated creatinine clearance of less than 30 ml/minute, and had either acute kidney injury or end-stage renal disease; several patients were taking renal replacement therapy. Fondaparinux was administered at an extended interval dosing regimen of 2.5 mg subcutaneously every 48 hours. Fondaparinux peak and trough anti-factor Xa levels were obtained. Lower extremity venous duplex studies were performed at baseline and study completion to assess for deep vein thrombosis (DVT), and patients were monitored for bleeding complications.. Thirty-two patients were enrolled. Patients received a median of four doses (interquartile range two to five) of fondaparinux. Fondaparinux peak (n=98) and trough (n=86) anti-factor Xa levels were 0.36 ± 0.18 mg/L and 0.17 ± 0.11 mg/L (mean ± SD), respectively, and were similar to levels reported in patients with normal renal function receiving conventional once-daily dosing. No lower extremity DVTs or suspected VTE events occurred. Two (6%) patients had significant bleeding events.. In critically ill patients with SRD, an extended interval fondaparinux dosing regimen of 2.5 mg every 48 hours for VTE prophylaxis achieved peak and trough anti-factor Xa levels similar to those reported in noncritically ill patients with normal renal function receiving once-daily fondaparinux. This regimen offers an alternative for patients with SRD when heparinoids must be avoided.

Topics: Acute Kidney Injury; Critical Illness; Drug Administration Schedule; Drug Monitoring; Factor Xa; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Kidney Failure, Chronic; Male; Middle Aged; Polysaccharides; Prospective Studies; Severity of Illness Index; Venous Thrombosis

Endovenous heat-induced thrombosis (EHIT) and deep venous thrombosis (DVT) are well-known complications after superficial endovenous thermoablation. We investigated the efficacy of rivaroxaban in preventing EHIT and DVT after endovenous laser ablation (EVLA).. We retrospectively analyzed a consecutive series of patients presenting with truncal varicosis class C. Between February 2009 and December 2015, 391 patients (473 limbs) were treated with EVLA of the truncal saphenous vein. The primary end point occurred in 13 of 166 (7.8%) and 14 of 225 (6.2%) after 1 week and in 13 of 166 (7.8%) and 15 of 225 (6.7%) after 4 weeks comparing the rivaroxaban and fondaparinux groups (P = .659). EHIT class 1 was observed in 20 patients (5.1%) and EHIT class 2 in five (1.3%). No patients had EHIT class 3 or 4. The incidence of DVT was one of 166 (0.6%) in the rivaroxaban group and two of 225 (0.9%) in the fondaparinux group (P = .750). Minor bleeding events occurred in 17 of 166 patients (10.2%) and in 20 of 225 patients (8.9%), respectively (P = .652). No major bleeding events were observed. Paresthesia was observed in 12.5% in the rivaroxaban group and in 17.8% in the fondaparinux group. No skin burns were observed.. Rivaroxaban offers an oral medication approach showing no difference in preventing EHIT and DVT compared with fondaparinux, without increased bleeding risk.

Topics: Administration, Cutaneous; Administration, Oral; Endovascular Procedures; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Humans; Laser Therapy; Male; Middle Aged; Polysaccharides; Retrospective Studies; Rivaroxaban; Saphenous Vein; Treatment Outcome; Varicose Veins; Venous Insufficiency; Venous Thrombosis

Topics: Adrenal Cortex Hormones; Antiphospholipid Syndrome; Cyanosis; Diagnosis, Differential; Drug Therapy, Combination; Fondaparinux; Foot Diseases; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Plasmapheresis; Polysaccharides; Venous Thrombosis

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

Some studies have cautioned about the possibility of bleeding complications with routine use of anticoagulants like fondaparinux (FPX) for thrombophylaxis after elective hip surgery. Overdosing or prolonged periods of anticoagulant use should be avoided. We trialed a new regimen using FPX and tranexamic acid (TA) to reduce the risk of bleeding complications while maintaining efficacy in preventing deep vein thrombosis (DVT). The present study evaluated the effectiveness and safety of this regimen in 391 consecutive patients. Each patient was assigned either the FPX group, administered a once-daily subcutaneous injection of 1.5 mg of FPX on postoperative days 2, 3, and 4; or the intermittent pneumatic compression (IPC) group, which used an IPC device continuously for 1-2 days with no administration of any anticoagulant drugs. Ultrasonography was performed to diagnose DVT in all patients. No cases of fatal or symptomatic pulmonary embolism were encountered in either group, but six patients (3.1 %) in the FPX group and nine patients (6.0 %) in the IPC group showed asymptomatic distal DVT. The incidence of DVT tended to be lower (p = 0.19), volumes of intraoperative (p < 0.01) and postoperative (p < 0.01) blood loss were significantly smaller, and hemoglobin level was significantly higher in the FPX group than in the IPC group (p < 0.01). Our new thrombophylactic regimen using FPX and TA appears effective and safe for use after elective hip surgery.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Elective Surgical Procedures; Female; Follow-Up Studies; Fondaparinux; Humans; Male; Middle Aged; Polysaccharides; Postoperative Complications; Prospective Studies; 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

Anti-Xa assays are useful for monitoring the effects of selective anti-Xa drugs, such as fondaparinux, in the prophylaxis of deep vein thrombosis. In the present study, anti-Xa activity was measured using three different assays, Testzym(®) Heparin S, STA(®)-Liquid Anti-Xa and HemosIL(®) Liquid Heparin. Anti-Xa activity in each assay gradually increased from day one after administration to day eight, and still remained on day 15. Although there were significant differences in anti-Xa activity among the three assays, the activity showed significant correlation across assays. There were no significant differences in the anti-Xa activity between patients with and without DVT or between patients with and without massive bleeding on day one before and after administration, day four, day eight and day 15. Anti-Xa activity in each assay was weakly correlated with antithrombin (AT) activity. The AT activity in patients were significantly higher on days four, eight and 15 compared with day one before and after administration, suggesting that AT activity increases following the administration of fondaparinux. The three anti-Xa assay kits tested are useful for monitoring fondaparinux treatment in orthopedic surgery patients.

Topics: Aged; Drug Monitoring; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Middle Aged; Orthopedic Procedures; Polysaccharides; Venous Thrombosis

Topics: Aged, 80 and over; Antibodies; Anticoagulants; Blood Platelets; Dalteparin; Female; Fondaparinux; Hip Fractures; Hirudins; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Morpholines; Peptide Fragments; Platelet Count; Polysaccharides; Recombinant Proteins; Rivaroxaban; Thiophenes; Thrombocytopenia; Venous Thrombosis

Topics: Blood Coagulation; Drug Administration Schedule; Drug Interactions; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Humans; Polysaccharides; Risk Factors; Thromboembolism; Treatment Outcome; Venous Thrombosis

Topics: Anticoagulants; Drug Administration Schedule; Early Medical Intervention; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Injections; Polysaccharides; Venous Thrombosis

Topics: Anticoagulants; Drug Hypersensitivity; Female; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Hypersensitivity, Immediate; Middle Aged; Polysaccharides; Tinzaparin; Venous Thrombosis

Heparin induced thrombocytopenia (HIT) is an immune-mediated adverse reaction characterized by thrombocytopenia and paradoxical arterial or venous thrombosis, due to the formation IgG antibodies directed to a multimolecular complex of heparin-platelet factor 4 (PF4). Fondaparinux is a selective factor Xa inhibitor with little affinity for PF4 and thus less likely to induce an immune response, making fondaparinux a potentially useful drug for the treatment of HIT. Herein we report the case of a 73 years old woman with HIT associated with arterial and venous thrombosis that was successfully treated with fondaparinux, with normalization of the platelet countand without progression of thrombosis.

Topics: Aged; Anticoagulants; Female; Fondaparinux; Heparin; Humans; Necrosis; Platelet Count; Platelet Factor 4; Polysaccharides; Thrombocytopenia; Treatment Outcome; Venous Thrombosis

Topics: Aged; Diagnosis, Differential; Disease Progression; Fondaparinux; Humans; Injections, Subcutaneous; Long-Term Care; Male; Polysaccharides; Thrombophlebitis; Venous Thrombosis

Portal vein thrombosis refers to an obstruction of blood flow in the portal vein; this rare disease can be both local and systemic. Local risk factors, accounting for about 70% of cases, can be abdominal cancers, inflammatory of infective diseases, surgical procedures or cirrhosis. A 62-year-old man, affected by hypertension and taking acetylsalicylic acid after a myocardial infarction in 1994, developed deep venous thrombosis on the right leg. Six months later the patient was admitted to the emergency unit due to abdominal pain. A CT scan revealed the presence of a complete splanchnic vein thrombosis and a primary tumor on the right kidney. The patient was treated with total parenteral nutrition and intravenous solution of heparin sodium first and then, because of occurrence of allergy, fondaparinux, with improvement of the abdominal pain. Subsequently he underwent right radical nephrectomy.

Topics: Anticoagulants; Carcinoma, Renal Cell; Drug Substitution; Fondaparinux; Heparin; Humans; Kidney Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Nephrectomy; Phlebography; Polysaccharides; Portal Vein; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis

Patients undergoing total knee arthroplasty (TKA) are at high risk of venous thromboembolism, manifesting as deep vein thrombosis (DVT) or pulmonary embolism. The purpose of this study is to evaluate the efficacy and safety of edoxaban 15 mg once daily (o.d.) for preventing DVT in patients undergoing TKA.. Three hundred patients undergoing primary TKA under general anaesthesia for osteoarthritis were enrolled in this study: 100 treated with enoxaparin 2,000 IU twice daily (b.i.d.), 100 treated with fondaparinux 1.5 mg o.d. and 100 treated with edoxaban 15 mg o.d.. All treatments were scheduled to continue for 14 days.. The incidence of DVT in patients treated with edoxaban 15 mg o.d. was lower than in patients with enoxaparin 2,000 IU b.i.d. and fondaparinux 1.5 mg o.d.. D-dimer levels were significantly lower in patients with edoxaban than in patients with enoxaparin and fondaparinux 1.5 mg o.d. on the first postoperative day; ΔHb levels were lower in patients with edoxaban than in patients with enoxaparin and fondaparinux on postoperative days, However, the difference was not statistically significant. Finally, the incidence of hepatic dysfunction was lower in patients with edoxaban than in patients with enoxaparin and fondaparinux.. Edoxaban 15 mg o.d. was more efficient than enoxaparin 2,000 IU b.i.d. and fondaparinux 1.5 mg o.d.. Furthermore, edoxaban was safe compared with enoxaparin and fondaparinux. Edoxaban, an orally administered direct factor Xa (FXa) inhibitor, may offer a new option for preventing DVT, with a level of evidence III.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Dose-Response Relationship, Drug; Enoxaparin; Female; Fondaparinux; Humans; Incidence; Knee Joint; Male; Osteoarthritis, Knee; Polysaccharides; Pyridines; Retrospective Studies; Thiazoles; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

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

Edoxaban is an oral and direct activated factor X inhibitor. In this study, the acute treatment effect of edoxaban on venous thrombosis is investigated in rats by single and multiple administrations, and compared to the conventional parenteral anticoagulants, enoxaparin and fondaparinux. Venous thrombus was induced in the inferior vena cava by partial stenosis plus topical application of 10% ferric chloride for 5min. After 1-h thrombus maturation, oral edoxaban and subcutaneous enoxaparin and fondaparinux were given. In the single administration experiment, thrombus weight was measured 1 or 4h after thrombus induction. In the multiple administration experiments, edoxaban was orally administered once daily (QD) and twice daily (BID) for 3 days. In the single administration experiment, oral administration of edoxaban (3.0 and 10mg/kg) 1h after thrombus formation significantly regressed the venous thrombus compared to the thrombus at 1h after thrombus formation. Similarly the significant venous thrombus regression was observed with enoxaparin (10mg/kg) and fondaparinux (0.30-3.0mg/kg). In the multiple administration experiment, both QD and BID administration of edoxaban at daily doses of 5 and 10mg/kg exerted significant treatment effects. QD administration of edoxaban including lower doses (1-10mg/kg) significantly reduced thrombus weight. Edoxaban administered QD and BID was effective in the treatment of venous thrombosis, and the treatment effect of edoxaban was comparable to the conventional parenteral anticoagulants. These data demonstrate the potential of edoxaban as an oral anticoagulant in the acute treatment of venous thromboembolism.

Topics: Administration, Oral; Animals; Anticoagulants; Antithrombin III; Disease Models, Animal; Drug Administration Schedule; Enoxaparin; Factor Xa Inhibitors; Fondaparinux; Male; Peptide Hydrolases; Polysaccharides; Pyridines; Rats; Rats, Wistar; Thiazoles; Venous Thrombosis

Topics: Aged; Antibodies; Anticoagulants; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Biomarkers; Chronic Disease; Drug Administration Schedule; Drug Monitoring; Fondaparinux; Humans; Male; Platelet Activation; Platelet Count; Polysaccharides; Predictive Value of Tests; Severity of Illness Index; Thrombocytopenia; Time Factors; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Blood Flow Velocity; Capillary Permeability; Diagnosis, Differential; Face; Facial Pain; Female; Fondaparinux; Humans; Neoplasms; Periodontitis; Polysaccharides; Remission, Spontaneous; Tooth Loss; Ultrasonography, Doppler, Color; Venous Thrombosis

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

Oral factor Xa (FXa) inhibitors are a novel class of anticoagulants that, unlike heparins, are expected to demonstrate antithrombotic effects independent of plasma antithrombin (AT) concentrations. We utilized heterozygous AT-deficient (AT+/-) mice to determine the impact of AT deficiency on anticoagulant and antithrombotic effects of edoxaban, a direct FXa inhibitor, and compared with heparins (fondaparinux, enoxaparin, and unfractionated heparin [UHF]).. The effects of edoxaban and heparins on in vitro prothrombin time and activated partial thromboplastin time were measured in plasma obtained from wild type (AT+/+) and AT+/- male mice. To assess the antithrombotic effects of these anticoagulants in vivo, venous thrombosis was induced in the inferior vena cava by FeCl3 treatment. Potency ratios of antithrombotic effects in AT+/- compared with AT+/+ mice were analyzed by a parallel line assay.. In vitro studies demonstrated that the clotting-time prolongation effects of edoxaban were not affected by heterozygous AT deficiency whereas those of AT-dependent anticoagulants were attenuated. In AT+/- mice, the antithrombotic effects of AT-dependent anticoagulants were less potent than those in AT+/+ mice. In contrast, edoxaban was equipotent in preventing thrombus formation in both wild-type and AT-deficient mice. The attenuated antithrombotic effects of fondaparinux, enoxaparin, and UFH in AT-deficient mice were restored by AT supplementation. Edoxaban exerts a comparable antithrombotic effect even in mice with low plasma AT antigen and activity to that in wild-type mice.. Edoxaban may potentially be prioritized over AT-dependent anticoagulants in patients with lower plasma AT concentration.

Topics: Animals; Anticoagulants; Antithrombin III; Blood Coagulation Tests; Enoxaparin; Factor Xa Inhibitors; Female; Fondaparinux; Gene Deletion; Hemostasis; Male; Mice; Mice, Inbred C57BL; Polysaccharides; Pyridines; Thiazoles; Venous Thrombosis

The relationships among the hemostatic markers, the development of deep vein thrombosis (DVT) and the withdrawal of fondaparinux due to a reduction in the hemoglobin levels were examined.. Two-hundred twenty-one Japanese patients who underwent major orthopedic surgery and were treated with 1.5mg of fondaparinux instead of 2.5mg of fondaparinux were studied. Forty-seven of 221 patients discontinued fondaparinux treatment (withdrawal group) and 37 patients developed DVT.. The age, frequency of total knee arthroplasty (TKA), withdrawal of fondaparinux, reduction of hemoglobin and the plasma levels of soluble fibrin (SF), D-dimer and fibrinogen and fibrin degradation product (FDP) on day 1 after the operation were significantly higher in the patients with DVT. Elevated SF, D-dimer or FDP levels were associated with the risk for DVT. The age, frequency of TKA or DVT, anti-Xa activity and the creatinine, FDP and D-dimer levels were significantly higher in the withdrawal group. An anti-Xa level >0.33 mg/l and an elevated D-dimer or FDP level were associated with the risk of withdrawal.. The age and SF levels, TKA and withdrawal of fondaparinux were related to the risk of DVT, and the anti-Xa activity, creatinine level and DVT were related to the risk of withdrawal of fondaparinux due to a reduction in hemoglobin.

Topics: Age Factors; Aged; Aged, 80 and over; Anemia; Anticoagulants; Arthroplasty, Replacement, Knee; Biomarkers; Factor Xa; Factor Xa Inhibitors; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fondaparinux; Hemoglobins; Humans; Male; Middle Aged; Polysaccharides; Risk Factors; Venous Thrombosis

The aim of Guidelines of the Angiology Section of the Slovak Medical Chamber (AS SMC) is to address a last european guidelines for the management of thrombophlebitis superficialis, as well as results in evidence based  medicine (EBM) in order to assess their contribution to our expanding knowledge on rational management of thrombophlebitis superficialis.. Superficial thrombophlebitis is a common disease, usually considered to be benign. However, the practice of systemic duplex ultrasonography has revealed a large number of cases of deep vein thrombosis concomitant with superficial thrombophlebitis. Assessment of clinical probability of deep vein thrombosis and venous tromboembolism and systematic duplex ultrasound investigation has been proposed in the initial management of superficial thrombophlebitis, to detect the presence of any underlying deep vein thrombosis. In contrast with extensive information on the management of deep vein thrombosis, there is little knowledge about the most appropriate treatment of the superficial thrombophlebitis.. The treatment of superficial thrombophlebitis should improve local symptoms while preventing the development of complications such as venous thromboembolism. The most effective therapeutic approach to superficial thrombophlebitis seems to be represented by fondaparinux (a synthetic selective indirect inhibitor of factor Xa) which have been shown to prevent VTE events and the extension and/ or recurrence of superficial thrombophlebitis.

Topics: Anticoagulants; Contrast Media; Czech Republic; Evidence-Based Medicine; Factor Xa Inhibitors; Fondaparinux; Humans; Polysaccharides; Recurrence; Thrombophlebitis; Ultrasonography, Doppler, Duplex; Venous Thrombosis

Patients undergoing knee arthroplasty are at high risk of developing post-operative deep vein thrombosis (DVT) or a pulmonary embolus (PE). Despite best efforts, the best prophylaxis for thromboembolic disease remains controversial. This article aims to update the reader on the newest guidelines concerning venous thromboembolism (VTE) prophylaxis for elective knee arthroplasty, highlighting their inconsistencies and why variations in recommendations exist.. The Medline database and the Internet were searched for VTE prophylaxis guidelines in English. 12 guidelines were found and compared. The comparison looked at the recommendations made, the grade of recommendation, the level of evidence available for these recommendations and any inconsistencies between the guidelines.. Nearly all the guidelines advocate the use of low molecular weight heparin (LMWH) and Fondaparinux. There is little consensus in terms of other recommended drugs, the doses, duration and their recommendation grades. There are marked differences in the methodologies adopted by the different guideline working-groups.. There is still uncertainty about the optimal methods of thromboprophylaxis in elective knee arthroplasty. Although there are always going to be disagreements about the endpoints amongst guideline makers, guidelines should achieve uniformity in their reporting of end-points, criteria for levels of evidence and recommendation grades, facilitating the clinician's decision-making process.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Decision Making; Decision Support Techniques; Dose-Response Relationship, Drug; Elective Surgical Procedures; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Venous Thrombosis

Topics: Aged; Anticoagulants; Blister; Blood Cell Count; Diagnosis, Differential; Eosinophils; Exanthema; Fondaparinux; Glucocorticoids; Humans; Hypersensitivity; Male; Polysaccharides; Prostatic Neoplasms; Surgical Tape; Thrombophilia; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Access Devices; Venous Thrombosis

According to the Comparison of Arixtra in Lower Limb Superficial Vein Thrombosis with Placebo (CALISTO) study, a recent randomized, controlled trial, prophylactic fondaparinux can prevent thrombotic complications following superficial vein thrombosis (SVT). The cost-effectiveness of this treatment remains to be determined.. We developed a decision-tree model comparing fondaparinux 2.5 mg daily for 45 days vs no treatment of SVT. It included all clinical events associated with SVT, its treatment, its complications, and all respective quality-adjustment factors. Data were mainly derived from the CALISTO study and the published literature. Measured outcomes comprised clinical events (VTE, major hemorrhage, death), quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). The analysis was conducted using a lifetime time horizon from a health-care system perspective. We performed one-way and probabilistic sensitivity analyses to evaluate parameter uncertainty.. In 10,000 patients, we estimated that fondaparinux would prevent 123 VTE events and two deaths. On a per-patient basis, the incremental QALY compared with no treatment was 0.04 (1 day) at an incremental cost of $1,734, resulting in an ICER of $500,000 per QALY. This result remained robust in the one-way sensitivity analyses, with an ICER remaining > $100,000 per QALY throughout all ranges. Based on probabilistic sensitivity analyses, the probability that fondaparinux was cost-effective was 1% at a willingness-to-pay of $100,000 per QALY.. Fondaparinux for 45 days does not appear to be cost-effective when treating patients with isolated SVT of the legs. A better value for money could be obtained in subgroups of patients with a higher incidence of VTE after SVT. Shorter durations of treatment should be further evaluated in future clinical studies.

Topics: Anticoagulants; Clinical Trials as Topic; Cost-Benefit Analysis; Decision Trees; Female; Fondaparinux; Humans; Leg; Male; Middle Aged; Polysaccharides; Quality-Adjusted Life Years; Venous Thrombosis

Fondaparinux is an accepted form of deep venous thrombosis prophylaxis after hip arthroplasty. Cited advantages of its use include once-daily administration, standard dosage, and superiority as compared with enoxaparin. However, there have been several case reports of serious associated bleeding complications. We describe the case of a 77-year-old woman who developed a massive leg hematoma in the operative extremity nearly 3 weeks after a primary total hip arthroplasty while on fondaparinux. The patient developed a compartment syndrome requiring decompression of the hematoma, fasciotomy, and subsequent additional plastic surgery for split thickness skin grafting.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Compartment Syndromes; Decompression, Surgical; Female; Fondaparinux; Hematoma; Humans; Leg; Osteoarthritis, Hip; Polysaccharides; Skin Transplantation; Surgery, Plastic; Treatment Outcome; Venous Thrombosis

There are many reports concerning the fondaparinux prophylaxis of deep vein thrombosis (DVT) after surgery, but little is known about the usefulness of diagnosing DVT by the thrombotic markers such as soluble fibrin (SF) and D-dimer in patients treated with fondaparinux. The main purpose of this study was to evaluate the accuracy of SF and D-dimer tests for DVT screening in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) treated with fondaparinux.. A total of 519 patients who underwent THA or TKA were evaluated. SF and D-dimer levels were evaluated on postoperative days 1, 4, 7, 14 and 21. DVT was confirmed by ultrasonography 4 days after surgery.. The incidence of DVT in patients treated with fondaparinux was significantly lower than in patients without fondaparinux. The SF test on postoperative day 1, and the D-dimer test on postoperative days 1, 4, and 7 were useful in untreated patients. However, in the patients treated with fondaparinux, the D-dimer test on postoperative day 7 only was useful for DVT screening.. The accuracy of SF and D-dimer test for the diagnosis of DVT was decreased by administration of fondaparinux. A new strategy for diagnosing DVT might be required for patients receiving fondaparinux.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fondaparinux; Humans; Male; Middle Aged; Polysaccharides; Postoperative Complications; Prospective Studies; Ultrasonography; Venous Thrombosis

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

In large randomized trials, thromboprophylaxis with fondaparinux in major orthopaedic surgery (MOS) has been shown to be superior to low molecular weight heparin (LMWH) prophylaxis with comparable safety. However, patients treated under trial conditions are different from unselected patients and efficacy and safety outcomes may be different in unselected patients in daily practice. We performed a retrospective cohort study to compare the efficacy and safety of venous thromboembolism (VTE) prophylaxis with fondaparinux or LMWH in 3896 consecutive patients undergoing major orthopaedic surgery at our centre.. All patients undergoing MOS between January 2006 and December 2009 were retrospectively analyzed using patient charts, hospital admission and discharge database, quality management database, transfusion unit database and VTE event documentation. VTE standard prophylaxis at our institution was LMWH (3000-6000 aXa units once daily) from January 2006 to December 2007 or fondaparinux 2.5 mg from January 2008 to December 2009. In these two large cohorts of unselected consecutive patients, in-hospital incidences of VTE, surgical complications, severe bleeding and death were evaluated.. Symptomatic VTE was found in 4.1% of patients in the LMWH group (62/1495 patients; 95% CI 0.032, 0.052) compared with 5.6% of patients receiving fondaparinux (112/1994 patients, 95% CI 0.047, 0.067; P= 0.047). Distal deep vein thrombosis (DVT) was significantly more frequent in the fondaparinux group (3.9%, 95% CI 0.031, 0.048; vs. 2.5%; 95% CI 0.018, 0.034; P= 0.021). No significant differences in the rates of major VTE or death were found. Rates of severe bleeding, transfusion of RBC concentrates, plasma and platelet concentrates were comparable between both treatment groups. However, patients receiving fondaparinux had significantly lower rates of surgical revisions (1.6%, 95% CI 0.011, 0.022 vs. 3.7%, 95% CI 0.028, 0.047; P < 0.001). Multivariate analysis revealed previous VTE (HR 18.2, 95% CI 11.6, 28.5; P < 0.001) and female gender (HR 1.9, 95% CI 1.3, 2.7; P < 0.001), but not fondaparinux prophylaxis (HR1.3, 95% CI 0.9, 1.7; P= 0.184) to be associated with significantly increased VTE risk.. Thromboprophylaxis with fondaparinux is less effective to prevent distal VTE than LMWH in unselected patients undergoing MOS, but is equally effective with regard to rates of major VTE and death. However, differences in efficacy of LMWH or fondaparinux are of little relevance compared with a history of VTE or female gender, which were found to be the main VTE risk factors in MOS. The safety profile of fondaparinux was comparable with LMWH with regard to rates of severe bleeding complications, but patients receiving fondaparinux had significantly less surgical complications requiring surgical revisions. Both our efficacy and safety findings differ from data derived from large phase III trials testing fondaparinux against LMWH in MOS, where overall rates of symptomatic VTE were lower and the safety profile of fondaparinux was different.. We conclude that the strict patient selection and surveillance in phase-III trials results in lower VTE and bleeding event rates compared with unselected routine patients. Consequently, the efficacy and safety profile of thromboprophylaxis regimens needs to be confirmed in large registries or phase IV trials of unselected patients.

Topics: Aged; Anticoagulants; Cohort Studies; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Randomized Controlled Trials as Topic; Registries; Retrospective Studies; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Deep venous thrombosis (DVT) is a life-threatening postoperative complication and occurs frequently after total-knee-replacement arthroplasty (TKA) and total-hip-replacement arthroplasty (THA). Fondaparinux (FPX) has been used to treat and prevent DVT, however interindividual difference of the drug efficacy exists. Therefore, this chart review was retrospectively conducted to research risk factors for a residual DVT after FPX treatment. Total of 112 patients undergone TKA or THA were treated with 2.5 mg FPX once a day between postoperative day (POD) 1 and 14 from July 2007 through December 2008. Among these patients, 30 patients who were detected DVT on POD 4 were enrolled in this study. Thirty patients were divided into two groups according to the presence (n=11) or absence (n=19) of DVT on POD14. The DVT (-) group had a significantly longer activated partial thromboplastin time (APTT, median 31.4 s) on POD 1 than the DVT (+) group (28.5 s) (p<0.02). Multivariate logistic regression analysis revealed that APTT lower than 28.5 seconds on POD1 was considered to be independent risk factor significantly contributing to residual DVT (odds ratio 17.5, 95% confidential interval 2.0-295.4, p=0.02). These findings should provide useful information for understanding the interindividual difference of the efficacy of FPX after TKA or THA.

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Fondaparinux; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Partial Thromboplastin Time; Polysaccharides; Postoperative Complications; Retrospective Studies; Risk Factors; Time Factors; Venous Thrombosis

Lower limb deep vein thrombosis (DVT) is the most frequent clinical manifestation of venous thromboembolism (VTE) and can involve proximal or distal veins. Distal DVT (dDVT) is often asymptomatic and data about its incidence and prognosis are scanty, especially in high risk medical inpatients. Therefore, no consensus exists on the value of detecting and treating dDVTs. Aim of study was to evaluate incidence and characteristics of asymptomatic isolated dDVT at admission in an Internal Medicine department.. Consecutive patients hospitalized for acute medical illnesses, in whom VTE was not the admission diagnosis, underwent Doppler Ultrasonography. For all patients with dDVT standard treatment with therapeutic doses of low molecular weight heparin or fondaparinux was proposed. Follow-up visits were scheduled at 1, 6 and 12weeks.. One-hundred-fifty-four patients were enrolled. In 4.5% a proximal DVT and in 16.2% an asymptomatic dDVT were found. Female sex, elevated age and renal and electrolyte abnormalities were significantly associated to dDVT (p=0.014, p=0.009 and p=0.046, respectively). Only low degree of mobility (LDM) was independently associated to dDVT [OR 7.97 (95%CI 2.42-26.27), p=0.001)]. A high mortality rate, not for VTE-related causes, was found, especially in the first week, among dDVT patients.. We found a high incidence of clinically silent dDVTs. LDM evaluation could be useful to select patients at high risk in whom to perform a search for dDVT.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Cohort Studies; Female; Follow-Up Studies; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Polysaccharides; Risk Factors; Sex Factors; Ultrasonography; Veins; Venous Thrombosis

Anticoagulation management of a patient complicated by heparin-induced thrombocytopenia is one of the challenging situations in open heart surgery. A 40-year old male receiving warfarin for anticoagulation was admitted to our clinic with a history of heparin-induced thrombocytopenia and a diagnosis of inferior caval thrombosis. He was scheduled for inferior vena cava thrombectomy via the inflow occlusion technique on the beating heart. Warfarin sodium was stopped three days prior to the operation while fondaparinux sodium was begun twice a day. The operation was successfully performed and no postoperative complications were observed.

Topics: Adult; Anticoagulants; Drug Administration Schedule; Drug Substitution; Fondaparinux; Heparin; Humans; Male; Polysaccharides; Thrombectomy; Thrombocytopenia; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Warfarin

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

Heparin-induced thrombocytopenia (HIT) is a well described side effect of heparin therapy. A 12-year-old boy developed deep-vein thrombosis. Risk factors for initial thrombosis are antiphospholipid syndrome and heterozygous mutation for prothrombin G20210A. Anticoagulant therapy with warfarin for 12 months was effective, but discontinuation of warfarin after 12 months resulted in recurrence of thrombosis. Unfractionated heparin (UFH) was initiated during the acute period, but heparin-induced thrombocytopenia developed. Transition from UFH to fondaparinux resulted in successful anticoagulation for a period of platelet recovery. We report a case of HIT developing with a background of prothrombotic genetic risk factors and antiphospholipid syndrome. This case study highlights several difficulties in pediatric HIT cases.

Topics: Anticoagulants; Antiphospholipid Syndrome; Child; Drug Substitution; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Mutation; Polysaccharides; Prothrombin; Risk Factors; Thrombocytopenia; 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

Hepcidin is a major regulator of iron homeostasis, and its expression in liver is regulated by iron, inflammation, and erythropoietic activity with mechanisms that involve bone morphogenetic proteins (BMPs) binding their receptors and coreceptors. Here we show that exogenous heparin strongly inhibited hepcidin expression in hepatic HepG2 cells at pharmacologic concentrations, with a mechanism that probably involves bone morphogenetic protein 6 sequestering and the blocking of SMAD signaling. Treatment of mice with pharmacologic doses of heparin inhibited liver hepcidin mRNA expression and SMAD phosphorylation, reduced spleen iron concentration, and increased serum iron. Moreover, we observed a strong reduction of serum hepcidin in 5 patients treated with heparin to prevent deep vein thrombosis, which was accompanied by an increase of serum iron and a reduction of C-reactive protein levels. The data show an unrecognized role for heparin in regulating iron homeostasis and indicate novel approaches to the treatment of iron-restricted iron deficiency anemia.

Topics: Aged; Aged, 80 and over; Animals; Anticoagulants; Antimicrobial Cationic Peptides; Blotting, Western; Bone Morphogenetic Protein 6; C-Reactive Protein; Female; Fondaparinux; Gene Expression Regulation; Hep G2 Cells; Heparin; Heparin, Low-Molecular-Weight; Hepcidins; Humans; Interleukin-6; Iron; Mice; Phosphorylation; Polysaccharides; Reverse Transcriptase Polymerase Chain Reaction; Smad Proteins; Spleen; Venous Thrombosis

Recent data on lower-limb superficial-vein thrombosis (SVT) may substantially impact its clinical management. Thus, 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 are 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. Based on these recent 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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Fondaparinux; Humans; Lower Extremity; Male; Middle Aged; Polysaccharides; Ultrasonography; Venous Thrombosis; Young Adult

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

Topics: Anticoagulants; Fondaparinux; Glomerular Filtration Rate; Hematoma; Humans; Kidney Diseases; Male; Middle Aged; Polysaccharides; Venous Thrombosis

Topics: Adenocarcinoma; Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Drug Resistance; Drug Therapy, Combination; Female; Fondaparinux; Humans; Middle Aged; Neoplasms, Unknown Primary; Polysaccharides; Syndrome; Treatment Outcome; Venous Thrombosis

Topics: Aged; Anticoagulants; Fondaparinux; Humans; Leg; Male; Polysaccharides; Stroke; Stroke Rehabilitation; Venous Thrombosis; Warfarin

No proven decline in mortality; no tangible prevention of pulmonary embolism; beware of bleeding.

Topics: Anticoagulants; Fondaparinux; Humans; Polysaccharides; Venous Thrombosis

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

Topics: Aged; Anesthesia, General; Antithrombins; Arthroplasty, Replacement, Knee; Female; Fondaparinux; Humans; Intermittent Pneumatic Compression Devices; Polysaccharides; Postoperative Complications; Tourniquets; Venous Thrombosis

A 22-year-old woman presented on the 10th post-partum day with deep vein thrombosis involving the right ilio-femoral and popliteal veins. This thrombosis was refractory to conventional anticoagulation and subsequently over a period of 6 weeks progressed to involve inferior vena cava and right ventricle. A diagnosis of Behçet's disease was made on the clinical grounds of fever, night sweats, and recurrent oral ulcers. In view of refractory thrombosis, anticoagulation with lepirudin was commenced followed by thrombolysis with streptokinase. After thrombolysis, anticoagulation was switched to fondaparinux. Intracardiac thrombus, oral ulcers, constitutional symptoms, and inflammatory indices resolved on 20 mg of oral prednisolone. This case highlights that management of thrombosis unresponsive to conventional anticoagulation requires careful consideration of the underlying conditions, the sites of thrombosis, as well as of the available treatment options. Intravenous lepirudin is a valuable therapeutic option when anticoagulation with warfarin or LMWH is not efficacious. Thrombolytic therapy may be used to treat intracardiac thrombi more rapidly, and possibly more efficiently, than surgery. The addition of corticosteroids or other immunosuppressive drugs is necessary in order to achieve a full resolution of thrombosis.

Topics: Anticoagulants; Behcet Syndrome; Female; Fibrinolytic Agents; Fondaparinux; Heart Ventricles; Hirudins; Humans; Iliac Vein; Polysaccharides; Popliteal Vein; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Recombinant Proteins; Streptokinase; Vena Cava, Inferior; Venous Thrombosis; Young Adult

Topics: Anticoagulants; Female; Fondaparinux; Hematocrit; Heparin; Hirudins; Humans; Middle Aged; Platelet Count; Polysaccharides; Recombinant Proteins; Thrombocytopenia; Ultrasonography; Venous Thrombosis

The successful use of fondaparinux in a hemodialysis patient with heparin-induced thrombocytopenia type II (HIT II) is reported.. An 85-year-old, 68-kg Caucasian woman came to the emergency department with shortness of breath and exertional chest pain radiating to the neck. Testing revealed non-ST-segment elevation myocardial infarction, severe coronary artery disease, mitral regurgitation, left ventricular dysfunction, an ejection fraction of 25-30%, and pulmonary arterial hypertension. I.V. unfractionated heparin was given for therapeutic anticoagulation per hospital protocol and discontinued on hospital day 3 before mitral valve repair and coronary bypass procedure. Postoperatively unfractionated heparin and low-molecular-weight heparin were avoided because of a reduction in the platelet count and suspicion of HIT. Instead, the patient was placed on sequential compression devices in addition to aspirin for prophylaxis of deep venous thrombosis. By postoperative day 6, the patient's platelet count dropped 76% from baseline, and the patient was found to have heparin-dependent platelet factor 4 antibodies. Argatroban infusion was initiated but discontinued after 2 days due to bleeding. Fondaparinux was ordered for anticoagulation therapy. By hospital day 8, the patient developed renal insufficiency requiring hemodialysis and adjustment of the fondaparinux regimen. During the 30-day course of fondaparinux, the patient did not experience thromboembolic events or bleeding and did not require transfusions. There was no clotting within hemodialysis membranes, and her hepatic function improved by the time of her discharge.. Fondaparinux was used in a hemodialysis patient with HIT II without the development of thromboembolic, hemodialysis-clotting, thrombocytopenic, or hemorrhagic complications. The patient's platelet count remained in the normal range during the 30-day course of fondaparinux.

Topics: Aged, 80 and over; Anticoagulants; Arginine; Coronary Artery Bypass; Female; Fondaparinux; Heparin; Humans; Mitral Valve; Pipecolic Acids; Platelet Aggregation Inhibitors; Platelet Count; Polysaccharides; Renal Dialysis; Sulfonamides; Thrombocytopenia; Venous Thrombosis

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Adrenal Cortex Hormones; Anticoagulants; Breast Neoplasms; Drug Hypersensitivity; Enoxaparin; Female; Fondaparinux; Histamine Antagonists; Humans; Hypersensitivity, Delayed; Lung Neoplasms; Middle Aged; Nadroparin; Patch Tests; Polysaccharides; Treatment Outcome; Vena Cava, Superior; Venous Thrombosis

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: Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Treatment Outcome; 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

Prevention of deep vein thrombosis has become standard of care in surgical and orthopaedic patients and it is gaining in attention in medical patients. However, there are still open questions related to its indication, to type and extent of prophylaxis and how to improve its efficacy and safety. In order to facilitate decision making to provide or to withhold prophylaxis, clinical risk assessment considering exposing and predisposing risk factors has proved to be of value. The exposing risk is characterised by type and extent of surgery or trauma, respectively, whereas the predisposing risk is determined by patient related risk factors. This has also been acknowledged in national and international guidelines. The choice of prophylactic modalities should be based on the combination of exposing and predisposing risk factors. Physical and pharmacological methods are available for primary prevention of VTE. The cornerstones of pharmacological prophylaxis have been subcutaneous injections of low molecular weight heparins or fondaparinux. Recently, also oral direct thrombin- and factor Xa-inhibitors have become available for patients undergoing hip or knee replacement surgery who always are at high risk for VTE complications.

Topics: Anticoagulants; Antithrombin III; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Risk Factors; Surgical Procedures, Operative; Thrombin; 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

Topics: Antibodies; Anticoagulants; Fondaparinux; Heparin; Humans; Platelet Count; Platelet Factor 4; Polysaccharides; Thrombocytopenia; Venous Thrombosis

The risk of thromboembolism is increased in inflammatory bowel disease and its symptoms may be overlooked. Furthermore, its treatment can be complex and is not without complications. We describe a case of an adolescent boy who developed a cerebral sinus venous thrombosis during a relapse of his ulcerative colitis and who, while on treatment with heparin, developed heparin-induced thrombocytopenia (HIT). The treatment was then switched to fondaparinux, a synthetic and selective inhibitor of activated factor X.

Topics: Adolescent; Colitis, Ulcerative; Fondaparinux; Heparin; Humans; Intracranial Thrombosis; Male; Polysaccharides; Risk Factors; Thrombocytopenia; Venous Thrombosis

Topics: Anticoagulants; Fondaparinux; Humans; Polysaccharides; Postoperative Complications; Randomized Controlled Trials as Topic; Research Design; Stockings, Compression; Treatment Outcome; Venous Thrombosis

Topics: Acute Disease; Anticoagulants; Arginine; Blood Coagulation; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; International Normalized Ratio; Pipecolic Acids; Platelet Count; Polysaccharides; Recombinant Proteins; Research Design; Sulfonamides; Thrombin; Thrombocytopenia; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Platelet Count; Polysaccharides; Recurrence; Safety; Thrombocytopenia; Venous Thrombosis

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

Deep vein thrombosis (DVT) remains a major burden and fondaparinux represents a new option for DVT therapy. We sought to determine if fondaparinux offered financial advantages over low-molecular weight heparin since it is given as a fixed dose over a wide range of patient weights rather then dosed directly on weight and because fondaparinux is not associated with heparin-induced thrombocytopenia (HIT).. We conducted a cost-minimization analysis comparing fondaparinux to enoxaparin for acute anticoagulation in DVT. We modeled a cohort of 1,000 hypothetical subjects and drew estimates for model inputs from the published literature. We completed multiple sensitivity analyses to asses the significance of our assumptions and used Monte Carlo simulation to estimate the 95% confidence intervals (CIs) around our estimation of the cost differential for the two agents.. In the base case, total disease management costs per patient with fondaparinux are US 472 dollars compared to 769 dollars with enoxaparin. The 95% CI around this difference ranges from US 48 dollars to US 401 dollars. The model was mildly sensitive to the pharmacy acquisition costs of fondaparinux and enoxaparin which was the major driver of overall costs. Neither the rates of nor costs associated with DVT recurrence, major bleeding, nor HIT substantially affected our observations. Breakeven analysis indicated our findings to be robust over a wide range of likely clinical scenarios.. From the perspective of a healthcare system, fondaparinux use offers an attractive economic alternative to other agents for initial DVT therapy. Expanded reliance on fondaparinux could potentially result in savings.

Topics: Body Weight; Costs and Cost Analysis; Enoxaparin; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Models, Economic; Polysaccharides; Recurrence; Thrombosis; Venous Thrombosis

Topics: Adult; Disease Management; Disease Progression; Fatal Outcome; Female; Fondaparinux; Humans; Lung Neoplasms; Polysaccharides; Recurrence; Thromboembolism; Venous Thrombosis

Current anticoagulant therapies for the prevention and treatment of thromboembolic disorders have many drawbacks: vitamin K antagonists interact with food and drugs and require frequent laboratory monitoring, and heparins require parenteral administration. Oral rivaroxaban (BAY 597939) is a new, highly selective and potent direct factor-Xa (FXa) inhibitor with a predictable pharmacodynamic and pharmacokinetic profile and could therefore be an attractive antithrombotic drug. It was the objective of this study to investigate the antithrombotic efficacy of oral rivaroxaban in two rabbit models of experimental venous thrombosis. In the venous stasis (prevention) model, animals were randomized to receive oral rivaroxaban 0.3, 1.0, 3.0 or 10.0 mg/kg or vehicle control. Thrombosis was induced by jugular vein stasis and injection of thromboplastin into the ear vein. In the venous thrombosis (treatment) model, intravenous (1.0 and 3.0 mg/kg) and oral (3.0 mg/kg) rivaroxaban was compared with intravenous nadroparin (40 U bolus and 20 U/h), fondaparinux (42 microg/kg) and vehicle control. Thrombus growth was assessed by measuring the accretion of radiolabelled fibrinogen into preformed clots in the jugular veins. Bleeding was assessed using an ear bleeding model. In the prevention model, rivaroxaban reduced thrombus formation dose-dependently (calculated ED(50) 1.3 mg/kg). In the treatment model, oral rivaroxaban (3.0 mg/kg) reduced thrombus growth to a similar extent to intravenous rivaroxaban (1.0 mg/kg), nadroparin and fondaparinux. Oral rivaroxaban did not prolong bleeding time. In conclusion, the orally available selective, direct FXa inhibitor rivaroxaban is effective in the prevention and treatment of venous thrombosis in two well-established models of experimental thrombosis.

Topics: Administration, Oral; Animals; Anticoagulants; Blood Coagulation Tests; Disease Models, Animal; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Infusions, Intravenous; Injections, Intravenous; Jugular Veins; Ligation; Morpholines; Nadroparin; Polysaccharides; Rabbits; Random Allocation; Rivaroxaban; Thiophenes; Thromboplastin; Venous Thrombosis

Topics: Adult; Anticoagulants; Drug Hypersensitivity; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Heparinoids; Humans; Polysaccharides; Pregnancy; Pregnancy Complications, Hematologic; Risk Factors; Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Drug Administration Schedule; Factor Xa Inhibitors; Female; Fibrin; Fondaparinux; Humans; Middle Aged; Perioperative Care; Phenprocoumon; Polysaccharides; Postoperative Hemorrhage; Surgical Procedures, Operative; Thromboembolism; Thrombophilia; Venous Thrombosis; Vitamin K

Topics: Adrenal Glands; Anticoagulants; Female; Fondaparinux; Heparin; Humans; Infarction; Middle Aged; Platelet Activation; Polysaccharides; Thrombocytopenia; Venous Thrombosis

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

Topics: Aged; Anticoagulants; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Polysaccharides; Thromboembolism; Venous Thrombosis

Hip arthroplasty and extended travel are each recognized as risk factors for venous thromboembolism (VTE). The safety of travel after hip arthroplasty is currently unknown. Patients who had traveled more than 200 miles within 6 weeks of a hip arthroplasty or hip resurfacing were identified and contacted. All patients received VTE chemoprophylaxis with enoxaparin, dalteparin, fondaparinox, or warfarin. A total of 608 patients traveled an average of 1377 miles at an average of 6.5 days after surgery. Among these patients, 462 traveled by airplane, 143 by car, and 3 by train. There were no deaths, no symptomatic pulmonary embolisms, and only 5 (0.82%) symptomatic deep venous thromboses. Nine (1.5%) patients experienced bleeding complications. With chemical VTE prophylaxis, extended travel within 6 weeks of hip arthroplasty surgery is associated with a low rate of symptomatic deep venous thrombosis, with no known pulmonary embolisms and no deaths.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Dalteparin; Enoxaparin; Fondaparinux; Hip Joint; Humans; Polysaccharides; Postoperative Complications; Risk Factors; Safety; Time Factors; Transportation; Travel; Venous Thromboembolism; Venous Thrombosis; Warfarin

The risk of venous thromboembolism in patients following arthroplasty may be reduced by continuing chemical thromboprophylaxis for up to 35 days post-operatively. This prospective cohort study investigated the compliance of 40 consecutive consenting patients undergoing lower limb arthroplasty with self-administration of a recommended subcutaneous chemotherapeutic agent for six weeks after surgery. Compliance was assessed by examination of the patient for signs of injection, number of syringes used, and a self-report diary at the end of the six-week period. A total of 40 patients, 15 men and 25 women, were recruited. One woman was excluded because immediate post-operative complications prevented her participation. Self-administration was considered feasible in 87% of patients (95% confidence interval (CI) 76 to 98) at the time of discharge. Among this group of 34 patients, 29 (85%) were compliant (95% CI 73 to 97). Patients can learn to self-administer subcutaneous injections of thromboprophylaxis, and compliance with extended prophylaxis to six weeks is good.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Feasibility Studies; Female; Fondaparinux; Hand; Humans; Injections, Subcutaneous; Male; Patient Compliance; Polysaccharides; Postoperative Care; Postoperative Complications; Prospective Studies; Self Administration; Thromboembolism; Venous Thrombosis

We report a patient who had a history of deep vein thrombosis in a previous pregnancy. She was treated with heparins without any reactions in the index pregnancy. Subsequently, when the patient became pregnant again, she developed an acute cutaneous reaction to the low molecular heparin enoxaparin 3 weeks after initiation of therapy. She developed a similar reaction to delteparin as well. She was therefore treated with warfarin until 36 weeks of gestation. Then she was treated with fondaparinux (Arixtra, Sanofi-Synthelabo, Paris, France) 2.5 mg daily for the remainder of the pregnancy. Delivery was at term by induction of labour. Fondaparinux was stopped on the day of the induction of labour. It was re-started 6 h post-delivery and the patient was anticoagulated with warfarin in the post-partum period. There were no bleeding tendencies or recurrences of thrombosis during fondaparinux therapy. Both mother and baby were well after delivery.

Topics: Anticoagulants; Drug Hypersensitivity; Female; Fibrinolytic Agents; Fondaparinux; Heparin; Humans; Live Birth; Polysaccharides; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Venous Thrombosis; Warfarin

Topics: Antibodies; Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Platelet Factor 4; Polysaccharides; Thrombocytopenia; Venous Thrombosis

Topics: Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Fondaparinux; Government Agencies; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Polysaccharides; Practice Guidelines as Topic; Surgical Procedures, Operative; United States; Venous Thrombosis

Topics: Acute Disease; Anticoagulants; Bed Rest; Disease-Free Survival; Fondaparinux; Humans; Inpatients; Polysaccharides; Randomized Controlled Trials as Topic; Thromboembolism; Treatment Outcome; Venous Thrombosis

Topics: Anticoagulants; Clinical Trials as Topic; Ethics, Research; Fondaparinux; Guidelines as Topic; Humans; Placebos; Polysaccharides; Research Design; Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Clinical Trials as Topic; Ethics, Research; Fondaparinux; Guidelines as Topic; Humans; Placebos; Polysaccharides; Research Design; Thromboembolism; Venous Thrombosis

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

Patients undergoing major orthopedic surgery face considerable risk of venous thromboembolism (VTE), which may be fatal unless they receive prophylactic treatment. Fondaparinux sodium is a new antithrombotic agent that is indicated for prophylaxis of VTE after major orthopedic surgery. This paper presents a cost-effectiveness analysis of fondaparinux sodium and enoxaparin sodium, the latter being the most commonly used agent for prophylaxis of VTE.. The analysis is based on an international simulation model, using Norwegian unit costs, and Norwegian data of 55 000 patients undergoing orthopedic surgery between 1999 and 2001. We estimated the expected incidence of VTE and VTE-related deaths, and expected costs of VTE-related care for each of the two prophylactic agents for different periods.. The results indicate that fondaparinux sodium is likely to be more effective than enoxaparin sodium in preventing the incidence of VTE. By day 90, fondaparinux sodium is expected to avoid 180 more VTE events, and between 8 and 33 more VTE-related deaths per 10,000 patients than enoxaparin sodium. Fondaparinux sodium is also a cost-saving option in short follow-up periods for hip fracture surgery. For extended follow-up periods (i.e. 5 years), fondaparinux sodium is also likely to represent the lower cost treatment option after total knee and hip replacement. The sensitivity analyses show that the main results are robust to changes in the most important parameters. Results are, however, sensitive to the price difference between the two drugs.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Enoxaparin; Female; Follow-Up Studies; Fondaparinux; Hip Fractures; Humans; Inpatients; Insurance, Health, Reimbursement; Length of Stay; Linear Models; Male; Norway; Polysaccharides; Thromboembolism; Venous Thrombosis

Treatment of a haemorrhagic shock after just a single dose of fondaparinux in an orthopaedic patient with reduced renal clearance is presented. Since all routine haemostatic parameters were nearly normal, single doses of rFVIIa (90 microg/kg) and of tranexamic acid (15 mg/kg) were administered to improve thrombin generation and reduce fibrinolysis. This case is the first showing the effectiveness of combining single doses of rFVIIa and tranexamic acid in controlling severe postoperative bleeding after fondaparinux.

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Arthroplasty, Replacement, Hip; Drug Therapy, Combination; Factor VII; Factor VIIa; Female; Fondaparinux; Humans; Intraoperative Period; Partial Thromboplastin Time; Platelet Count; Polysaccharides; Postoperative Hemorrhage; Prothrombin Time; Recombinant Proteins; Tranexamic Acid; Venous Thrombosis

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: Anticoagulants; Drug Costs; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Humans; Polysaccharides; Postoperative Complications; Premedication; Venous Thrombosis

Therapy for venous thromboembolism (VTE) currently involves a minimum of 3 months of anticoagulation. After cessation of therapy, however, recurrent venous thrombosis occurs at rates of 6 to 9% per year. Clinical trials have demonstrated the benefits of extending anticoagulation beyond 3 months for the prevention of recurrent VTE events. Despite this, many eligible patients do not receive the required thromboprophylaxis and the incidence of recurrent VTE remains too high for a preventable condition. A reason for failure to use prophylaxis is the fear of bleeding complications with current oral anticoagulants such as warfarin. Warfarin has an unpredictable pharmacokinetic profile and a variable dose-response relationship that requires frequent coagulation monitoring and dose adjustments to maintain a target intensity that is both safe and effective. Alternative strategies for long-term prophylaxis, which may potentially provide more consistent anticoagulant responses and reduce coagulation monitoring requirements, include the use of low-molecular-weight heparin (LMWH), treatment with warfarin at a lower intensity, and the introduction of novel anticoagulants. The long-term use of LMWH has been found to be a particularly favorable treatment option for cancer patients in whom it is difficult to control the intensity of anticoagulation. In clinical trials, LMWH significantly reduced the risk of recurrent VTE without increasing bleeding risk. The parenteral administration of the LMWHs, however, is a drawback for long-term use in the outpatient setting. A clinical trial assessing the efficacy and safety of long-term low-intensity warfarin treatment found this therapy to be better than placebo, but another study showed that conventional intensity warfarin was significantly more efficacious than low-intensity warfarin. New therapies in development that may offer improved safety-efficacy profiles are the synthetic pentasaccharides fondaparinux and idraparinux and the oral direct thrombin inhibitor ximelagatran. Parenterally administered fondaparinux has been shown to be as effective as LMWH for the acute treatment (5 to 7 days) of symptomatic deep vein thrombosis. Idraparinux, with once-weekly parenteral dosing, is currently being assessed in phase III clinical trials for the long-term secondary prevention of VTE. Ximelagatran is the first oral agent in the new class direct thrombin inhibitors. With a fast onset of action and oral administration, ximelagatran is a

Topics: Anticoagulants; Azetidines; Benzylamines; Chemical and Drug Induced Liver Injury; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Myocardial Ischemia; Oligosaccharides; Polysaccharides; Recurrence; Thrombin; Time Factors; Venous Thrombosis; Warfarin

Fondaparinux sodium (fondaparinux) is a synthetic sulfated pentasaccharide anticoagulant developed from the antithrombin binding moiety of heparin. Through the activation of antithrombin it inhibits Factor Xa, the activation of thrombin, and the subsequent coagulation cascade. Fondaparinux is approved in Europe and the US for the treatment of acute venous thromboembolism (VTE), including both deep vein thrombosis (DVT) and pulmonary embolism (PE), when used in conjunction with warfarin. In phase III clinical trials, subcutaneous fondaparinux was noninferior to subcutaneous enoxaparin or intravenous unfractionated heparin (UFH) in the prevention of recurrent symptomatic VTE in patients with acute DVT and PE, respectively, and equally well tolerated. It thus provides a valuable alternative to UFH and low-molecular weight heparins in the treatment of acute VTE, particularly in the outpatient setting.

Topics: Acute Disease; Anticoagulants; Antithrombin III; Clinical Trials as Topic; Fondaparinux; Humans; Polysaccharides; Venous Thrombosis

Low-molecular-weight heparins share many properties and are commonly referred to as a group, but structurally and pharmacologically they are dissimilar. The size spectrum of the heparin molecules varies between the different products and as assessed in vitro, their anticoagulant properties differ. In particular, the ratio anti-factor Xa : anti-factor IIa activities varies. The clinical consequences of these differences are unknown. The efficacy and safety of two different low-molecular-weight heparins have been compared in only a few clinical studies; no significant differences in outcome were shown. However, low-molecular-weight heparins should be used according to the approved indication for each product and in doses shown effective and safe in clinical studies. A change from one low-molecular-weight heparin to another in the same patient should be avoided. Fondaparinux is a synthetic penta-saccharide which may be regarded as an extreme low-molecular-weight heparin with a ratio of anti-factor Xa : anti-factor IIa activity as 1 : 0, and with a promising efficacy/safety profile. So far, the approved clinical indication for its use is limited to prophylaxis in orthopaedic surgery.

Topics: Anticoagulants; Coronary Disease; Dalteparin; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Molecular Structure; Polysaccharides; Thrombolytic Therapy; Tinzaparin; Venous Thrombosis

Topics: Anticoagulants; Drug Eruptions; Drug Hypersensitivity; Female; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Molecular Weight; Polysaccharides; Venous Thrombosis

Prophylactic treatment against deep vein thrombosis has become a routine part of surgical treatment. The indications and the form of prophylaxis selected depend on the patient's individual risk profile, which is determined in turn by a combination of exposing and predisposing risk factors. The exposing risk factors depend on the type of surgery and trauma the patient is exposed to, while the predisposing risks are determined by factors peculiar to the patient. This review deals with the modalities of prophylaxis currently available, pharmacological details relating to these, and their clinical significance. In addition, evidence-based data, recommendations for the duration of prophylaxis derived from official guidelines, and medicolegal aspects are discussed. The development of new anticoagulants is expanding the range of prophylactic methods, which means further information is needed.

Topics: Anticoagulants; Bandages; Evidence-Based Medicine; Fibrinolytic Agents; Fondaparinux; Heparin; Humans; Phenprocoumon; Polysaccharides; Postoperative Care; Postoperative Complications; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Surgery Department, Hospital; Venous Thrombosis

Topics: Aged; Body Weight; Cause of Death; Double-Blind Method; Drug Administration Schedule; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Kidney; Male; Middle Aged; Polysaccharides; Recurrence; Treatment Outcome; Venous Thrombosis; Vitamin K

To determine the cost effectiveness of fondaparinux sodium compared with enoxaparin sodium for prophylaxis against venous thromboembolism in patients undergoing major orthopaedic surgery.. Using a cohort simulation model, two primary analyses were conducted from the perspective of the US healthcare payer. Probabilities for a trial-based analysis were obtained from patients participating in the fondaparinux clinical trial programme supplemented with data from published literature. Probabilities for a label-based analysis were estimated for a hypothetical cohort of US patients receiving either fondaparinux or enoxaparin as recommended by US FDA-approved labelling. Resource use and costs were obtained from large US healthcare databases. Outcome measures were rates of symptomatic thromboembolic events and healthcare costs. Costs were in 2003 values.. In the trial-based analysis, fondaparinux was estimated to prevent 15.1 symptomatic venous thromboembolic events (per 1,000 patients) at 3 months for patients undergoing major orthopaedic surgery compared with enoxaparin. The cost savings (per patient) of using fondaparinux over enoxaparin are US 61 dollars at 30 days, US 89 dollars at 3 months, and US 155 dollars at 5 years. In the label-based analysis, fondaparinux was estimated to prevent 17.8 venous thromboembolic events (per 1,000 patients) at 3 months compared with enoxaparin, producing savings per patient of US 25 dollars at discharge, US 112 dollars over 1 month, US 141 dollars over 3 months and US 234 dollars over 5 years. Results remain robust to clinically plausible variation in input parameters and assumptions.. Our model suggests that fondaparinux, when compared with the current standard regimen of enoxaparin for prophylaxis of venous thromboembolism in major orthopaedic surgery, improves outcomes and is cost saving from a US healthcare-payer perspective over the broad range of assumptions evaluated.

Topics: Aged; Aged, 80 and over; Anticoagulants; Clinical Trials as Topic; Cohort Studies; Cost-Benefit Analysis; Decision Support Techniques; Enoxaparin; Fondaparinux; Health Care Costs; Hip Fractures; Humans; Models, Economic; Orthopedic Procedures; Polysaccharides; Treatment Outcome; Venous Thrombosis

Patients undergoing hip arthroplasty are at high risk for developing venous thromboembolic events (VTE) postoperatively in the absence of prophylaxis. In this study, a cost analysis comparing efficacy and safety data from a published trial evaluating fondaparinux and enoxaparin as VTE prophylaxis in hip replacement patients was performed. Incremental cost effectiveness ratios were calculated to determine cost per VTE avoided. Additionally, cost per death averted and cost per life year gained were calculated. Fondaparinux proved to offer minor cost savings when compared with 30 mg enoxaparin every 12 h for costs per VTE avoided, costs per death averted, and costs per life year gained. Sensitivity analyses support these findings.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Costs and Cost Analysis; Elective Surgical Procedures; Enoxaparin; Fondaparinux; Humans; Polysaccharides; Thromboembolism; Venous Thrombosis

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

Fondaparinux and enoxaparin are both effective and safe in preventing post-operative venous thromboembolism. However, neither of them significantly influence the conventional clotting tests. We compared the influence of clinically relevant concentrations of fondaparinux and enoxaparin on normal whole blood (WB) thromboelastographic profiles after triggering TF-pathway with minimal amount of thromboplastin. Diluted thromboplastin was added to WB samples supplemented with buffer (control), fondaparinux (0.25; 0.5; 1 microg/ml), or enoxaparin (0.1; 0.5; 1 anti-Xa IU/ml). Four parameters were analyzed, R: clotting time, K: time required to reach an amplitude of 20 mm, alpha angle: measurement reflecting clot development kinetics and MA: maximal amplitude. At concentrations used in prophylaxis, both enoxaparin (0.1 anti-Xa IU/ml) and fondaparinux (0.25 microg/ml which correspond to 0.27 anti-Xa IU/ml) significantly prolonged the R and K times, but did not significantly modify the alpha angle as compared to the control. At concentrations observed after administration of curative doses for the treatment of DVT (> or = 0.5 anti-Xa IU/ml for enoxaparin and > or = 0.5 microg/ml for fondaparinux) both drugs induced a significant increase of R and K times, and a significant decrease of the alpha angle (p < 0.05). In contrast to fondaparinux, enoxaparin at concentrations equal to or higher than 0.5 anti-Xa IU/ml significantly reduced MA. The present study provides evidence that the whole blood TF-triggered TEG assay is sensitive to the presence of clinically relevant concentrations of enoxaparin or fondaparinux. Moreover, the angle may be used in order to distinguish the effect of prophylactic and therapeutic concentrations, since it was significantly reduced by the later ones. Further studies are needed to evaluate the clinical usefulness of whole blood TF-triggered TEG assay for the monitoring of treatment with enoxaparin or fondaparinux.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Dose-Response Relationship, Drug; Enoxaparin; Fondaparinux; Humans; In Vitro Techniques; Kinetics; Polysaccharides; Thrombelastography; Thrombin; Thromboembolism; Thromboplastin; Time Factors; Venous Thrombosis

Drug prevention and treatment of venous thromboses and thromboembolism remain a serious problem in the management of surgical and therapeutic patients. Pentasaccharides, novel anticoagulants selectively blocking Xe factor have a great potential for their use in the given area. It has been demonstrated at the preliminary stages of the study of these antithrombotic agents that their pharmacokinetics permits subcutaneous drug injection once a day (for fondaparinux) and once for 7 days (for indraparinux) without the necessity of making routine coagulologic control. The drugs are marked by bioavailability approximating 100%, linear dose-dependent pharmacokinetic profile at subcutaneous injection; they do not undergo metabolism and are excreted largely with urine. Fondaparinux, the first representative of this class anticoagulants, has evidence for the effectiveness and safety, obtained in large randomized studies carried out in orthopedic and traumatologic patients. The given paper reports the new positive data on evaluation of the preventive action of fondaparinux in therapeutic subjects end patients who had undergone abdominal surgical interventions. Moreover, in large comparative studies , this anticoagulant did yield to the standard agents applied to the treatment of thrombosis of the deep veins and thromboembolism of pulmonary artery branches. Being more handy in use fondaparinux is capable of replacing antithrombotic agents (without efficacy and safety loss) used nowadays for preventive and therapeutic purposes. In the event of successful completion of the evaluation of idraparinux, another pentasaccharide intended for many months of anticoagulant treatment, the goal-oriented use of pentasaccharides is potentially capable of supplanting all the "old" antithrombotic agents from the schedule of the short-term and prolonged prevention and treatment of venous thromboses and thromboembolism.

Topics: Adult; Anticoagulants; Complement Factor H; Dalteparin; Fondaparinux; Humans; Middle Aged; Polysaccharides; Postoperative Complications; Randomized Controlled Trials as Topic; Thromboembolism; Venous Thrombosis

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Fondaparinux; Fracture Fixation, Internal; Hip Fractures; Humans; Polysaccharides; Thromboembolism; United Kingdom; Venous Thrombosis

Two new classes of anticoagulants in development at the present time [anti-factor Xa and anti-factor IIa (direct antithrombin) agents] should change our future strategies for prevention and treatment of venous thromboembolic events. Among the anti-factor Xa, the pentasaccharides are initiating their clinical use. Fondaparinux, the synthetic form of the natural pentasaccharide is active in prevention and treatment of venous thromboembolic and coronary thrombotic events. A modified form (idraparinux) whose pharmacokinetics allows one administration only once a week should have the same type of efficacy. Among direct antithrombin agents, hirudin and derivatives have been developed in the past decade burt are not routinely used. Synthetic direct antithrombins allowing oral route are currently developed: Exanta with the most advanced development, is active in prevention and treatment of venous thromboembolic and coronary thrombotic events. It could allow (if confirmed by clinical trials) a complete oral treatment of deep vein thrombosis without any biological monitoring. Exanta is also active in the prevention of arterial thromboembolic events on atrial fibrillation. Other molecular forms of synthetic per os direct antithrombin are also in development. But molecules aimed at other targets are also tested: the most advanced are those antagonizing the initial phase of tissue factor activation of factor VII but other strategies are being tested such as stimulation of fibrinolysis.

Topics: Antithrombins; Azetidines; Benzylamines; Fibrinolytic Agents; Fondaparinux; Forecasting; Humans; Insect Proteins; Polysaccharides; Salivary Proteins and Peptides; Thromboembolism; Venous Thrombosis

Patients undergoing hip arthroplasty in the absence of prophylaxis for venous thromboembolic events (VTEs) are at high risk for experiencing postoperative VTEs. In the study reported here, we performed cost analyses involving efficacy and safety data from clinical trials evaluating fondaparinux and enoxaparin as VTE prophylaxis. Incremental cost-effectiveness ratios were calculated to determine cost per VTE avoided. In addition, cost per death averted and cost per life-year gained were calculated. Once-daily fondaparinux proved to be more cost-effective than once-daily enoxaparin 40 mg but less cost-effective than twice-daily enoxaparin 30 mg.

Topics: Aged; Arthroplasty, Replacement, Hip; Costs and Cost Analysis; Drug Costs; Enoxaparin; Female; Fibrinolytic Agents; Fondaparinux; Humans; Life Expectancy; Male; Middle Aged; Polysaccharides; Postoperative Complications; Preoperative Care; Venous Thrombosis

Topics: Anticoagulants; Fondaparinux; Humans; Polysaccharides; Venous Thrombosis

Topics: Anticoagulants; Clinical Trials as Topic; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Orthopedic Procedures; Polysaccharides; Venous Thrombosis

Topics: Anticoagulants; Azetidines; Benzylamines; Clinical Trials as Topic; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Venous Thrombosis

Topics: Anticoagulants; Arthroplasty, Replacement; Clinical Trials as Topic; Fondaparinux; Humans; Orthopedic Procedures; Osteoarthritis, Hip; Osteoarthritis, Knee; Polysaccharides; Postoperative Complications; Research Design; Thromboembolism; Treatment Outcome; Venous Thrombosis

Total knee arthroplasty (TKA) has been in development since the early 1970s. Insall and others established the principles of ligament balance and overall alignment for implant success. Repicci introduced the concept of minimally invasive surgery in the early 1990s using the unicondylar prosthesis. As the outcomes of minimally invasive surgeries continued to improve when using a unicondylar prosthesis, it was logical to attempt a minimally invasive TKA. The author and his team have performed 120 minimally invasive TKAs over the past 2 years. Early results show that a minimally invasive approach produces better early motion, less blood loss, less pain, and a shorter hospital stay than the standard TKA with no compromise in accuracy.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Cohort Studies; Female; Follow-Up Studies; Fondaparinux; Humans; Male; Middle Aged; Minimally Invasive Surgical Procedures; Osteoarthritis, Knee; Polysaccharides; Postoperative Care; Postoperative Complications; Recovery of Function; Retrospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome; Venous Thrombosis

The selective antithrombotic fondaparinux is more effective than the low-molecular-weight heparin enoxaparin for prevention of venous thromboembolism (deep-vein thrombosis [DVT] or pulmonary embolism) in patients undergoing major orthopedic surgery, but its cost-effectiveness is undetermined.. To evaluate the cost-effectiveness of fondaparinux relative to enoxaparin as prophylaxis against venous thromboembolism (VTE) for patients undergoing total hip replacement, total knee replacement or hip fracture surgery in the UK.. A decision analysis model was created simulating the impact of fondaparinux and enoxaparin on patient outcomes and costs over various time points up to 5 years following surgery. The main outcome measures were treatment costs per patient and the incidence of clinical VTE and VTE-related deaths. A weighted (combined) cohort reflects the proportion of patients undergoing these procedures in 2000/2001.. In the combined cohort, compared with enoxaparin, fondaparinux is expected to produce 20 fewer clinical VTE events and 3.2 fewer VTE-related deaths per 1000 procedures at 5 years. Cost savings at 5 years are pound 27 per patient with fondaparinux (discounted at 6% per year). In each of the three surgical groups, fondaparinux leads to lower expected costs per patient and to a smaller number of VTE events and VTE-related deaths. RESULTS are sensitive to the price difference between fondaparinux and enoxaparin and variation in the rate of late DVT. The analysis is robust to variations in all other key parameters.. Compared with enoxaparin, fondaparinux is more effective and reduces costs to the healthcare system. At current prices, fondaparinux is the recommended strategy in the UK for prophylaxis following major orthopedic surgery.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cohort Studies; Cost-Benefit Analysis; Enoxaparin; Fondaparinux; Hip Fractures; Humans; Models, Theoretical; Orthopedics; Polysaccharides; Sensitivity and Specificity; Thromboembolism; Treatment Outcome; Venous Thrombosis

Topics: Clinical Trials as Topic; Drug Approval; Drug Industry; Fibrinolytic Agents; Financing, Organized; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Research Design; Research Support as Topic; Thromboembolism; Treatment Outcome; Venous Thrombosis

Topics: Fibrinolytic Agents; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Research Design; Thromboembolism; Treatment Outcome; Venous Thrombosis

Topics: Clinical Trials as Topic; Drug Industry; Fibrinolytic Agents; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Research Design; Research Support as Topic; Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Critical Care; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Postoperative Complications; Venous Thrombosis

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Diagnosis, Differential; Female; Fondaparinux; Heparinoids; Heparitin Sulfate; Humans; Hypersensitivity, Delayed; Injections; Intradermal Tests; Middle Aged; Polysaccharides; Venous Thrombosis

Topics: Anticoagulants; Arthroplasty, Replacement; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Practice Guidelines as Topic; Venous Thrombosis; Warfarin

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Controlled Clinical Trials as Topic; Fondaparinux; Fracture Fixation, Internal; Hip Fractures; Humans; Polysaccharides; Thromboembolism; Treatment Outcome; Venous Thrombosis

Topics: Arthroplasty, Replacement, Hip; Drug Administration Schedule; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Humans; Polysaccharides; Postoperative Complications; Thromboembolism; Venous Thrombosis

Topics: Arthroplasty, Replacement, Hip; Drug Administration Schedule; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Polysaccharides; Postoperative Complications; Thromboembolism; Venous Thrombosis

Topics: Arthroplasty, Replacement, Hip; Drug Administration Schedule; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Humans; Polysaccharides; Postoperative Complications; Thromboembolism; Venous Thrombosis

Topics: Arthroplasty; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Humans; Polysaccharides; Postoperative Complications; Venous Thrombosis

Topics: Arthroplasty; Enoxaparin; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Postoperative Complications; Venous Thrombosis

Topics: Drug Administration Schedule; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hip Fractures; Humans; Polysaccharides; Postoperative Complications; Thromboembolism; Venous Thrombosis

Topics: Drug Administration Schedule; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Humans; Polysaccharides; Postoperative Complications; Venous Thrombosis

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

Topics: Enoxaparin; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Thromboembolism; Venous Thrombosis

Topics: Anticoagulants; Clinical Trials as Topic; Dose-Response Relationship, Drug; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Injections, Intravenous; Polysaccharides; Postoperative Complications; Venous Thrombosis

Topics: Arthroplasty, Replacement, Hip; Clinical Trials as Topic; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Postoperative Complications; Venous Thrombosis

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