fondaparinux and Venous-Thromboembolism

To systematically review the efficacy of 11 anticoagulants in the treatment of venous thromboembolism (VTE) after total hip or knee arthroplasty.. PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine databases were electronically searched for studies assessing the efficacy of different anticoagulants for the prevention of VTE after total hip or knee arthroplasty from January 1, 2010, to January 27, 2022. Two reviewers independently screened the literature, extracted data, and graded the evidence using Confidence in Network Meta-Analysis. The network meta-analysis was then performed using Stata 16.0 software and R 4.1.0 software.. A total of 61 articles were included. The results of network meta-analysis showed that apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban were the most effective anticoagulants for the prevention of deep vein thrombosis in patients undergoing total hip or knee arthroplasty (P < .05), while there was no difference in the efficacy among the anticoagulants for the prevention of pulmonary embolism (P > .05).. Apixaban, edoxaban, fondaparinux, rivaroxaban, and darexaban have the best efficacy for the prevention of VTE after total hip or knee arthroplasty.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Fondaparinux; Humans; Network Meta-Analysis; Rivaroxaban; Venous Thromboembolism

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

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

Low molecular weight heparin, enoxaparin, has been one of most used drugs to fight the SARS-CoV-2 pandemic. Pharmacological properties of heparin recognize its specific ability, as with other oligosaccharides and glycosaminoglycan, to bind several types of viruses during their pass through the extracellular matrix of the respiratory tract, as well as its anticoagulant activity to prevent venous thromboembolism. Antithrombotic actions of enoxaparin have been testified both for inpatients with COVID-19 in regular ward and for inpatients in Intensive Care Units (ICUs). Prophylactic doses seem to be able to prevent venous thromboembolism (VTE) in inpatients in the regular ward, while intermediate or therapeutic doses have been frequently adopted for inpatients with COVID-19 in ICU. On the other hand, although we reported several useful actions of heparin for inpatients with COVID-19, an increased rate of bleeding has been recorded, and it may be related to several conditions such as underlying diseases with increased risks of bleeding, increased doses or prolonged administration of heparin, personal trend to bleed, and so on.

Topics: Anticoagulants; COVID-19; Enoxaparin; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Inpatients; Intensive Care Units; Pandemics; SARS-CoV-2; Venous Thromboembolism

The objective of this study is to comprehensively review the efficacy and safety data of low-molecular-weight heparins (LMWHs) and fondaparinux in pediatric patients with obesity.. A comprehensive literature search of PubMed, SCOPUS, CINAHL, Academic Search Complete, PsycInfo, Cochrane Library, and Web of Science databases was conducted (1900 to July 2020). Search terms utilized included. Studies that reported pediatric patients with described overweight or obesity and utilized LMWHs or fondaparinux were considered.. Of 207 studies screened, 12 were included. Average dose reductions of 12.9% to 37.3% from the starting dose were observed with treatment indications of enoxaparin and increased up to 27.3% for prophylactic indications. Trends could not be concluded in the dalteparin and fondaparinux studies. Four thrombotic and 15 bleeding events were reported in the studies.. Pediatric patients with obesity may initially be underdosed or overdosed with enoxaparin compared with children with healthy body weight, depending on the indication.. Pediatric patients with obesity may benefit from proactively adjusting enoxaparin dosing on initiation of therapy. Further studies are needed for dalteparin and fondaparinux in these populations. Clinical controversy exists with the relevance of monitoring these high-risk medications for therapeutic and prophylactic indications. Thrombotic and hemorrhagic events were similar to reported adult outcomes.

Topics: Anticoagulants; Child; Child, Preschool; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Obesity; Retrospective Studies; Thrombosis; Venous Thromboembolism

Topics: Administration, Oral; Factor Xa Inhibitors; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Patient Compliance; Pyrazoles; Pyridones; Venous Thromboembolism; Warfarin

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

Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

Topics: Anticoagulants; Central Venous Catheters; Factor Xa Inhibitors; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Vena Cava Filters; Venous Thromboembolism; Vitamin K

Low molecular weight heparins and fondaparinux have been the cornerstones for prevention of venous thromboembolism (VTE) in acutely ill medical patients for almost two decades. Guidelines recommend the use of these parenteral anticoagulants for 6 to 14 days but advise against extended-duration thromboprophylaxis after hospital discharge because no compelling scientific evidence has been provided for pharmacological prophylaxis beyond hospital stay. Five large randomized clinical trials, one with low molecular weight heparin and four with nonvitamin K antagonist oral anticoagulants, have failed to show significant clinically relevant benefit in this indication. Obviously, the development of VTE is more complex in medical patients than in patients undergoing major surgical procedures. Thus, it can be expected that guideline recommendations for VTE prevention with low molecular weight heparins or fondaparinux in medical patients will remain unchanged in 2019.. Über zwei Jahrzehnte waren niedermolekulare Heparine und Fondaparinux die Eckpfeiler der venösen Thromboembolie-Prophylaxe für Patienten mit akuten internistischen Erkrankungen. In den Leitlinien wird diese Art der Prophylaxe für 6 bis 14 Tage empfohlen, jedoch wird von einer verlängerten Dauer der Prophylaxe über den Krankenhausaufenthalt hinaus wegen fehlender wissenschaftlicher Evidenz abgeraten. In fünf großen randomisierten Studien, davon eine mit niedermolekularem Heparin und vier mit Nicht-Vitamin K antagonistischen oralen Antikoagulanzien, konnte für diese Indikation kein signifikanter, klinisch relevanter Vorteil nachgewiesen werden. Vermutlich ist die Entstehung venöser Thromboembolien bei internistischen Patienten komplexer als bei Patienten mit chirurgischen Eingriffen. Deshalb ist zu erwarten, dass die Leitlinienempfehlungen zur venösen Thromboembolie-Prophylaxe mit niedermolekularen Heparinen oder Fondaparinux für internistische Patienten auch im Jahr 2019 unverändert bleiben.

Topics: Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Venous Thromboembolism

Background Fondaparinux sodium has been compared with low-molecular-weight heparins ( LMWH ) in randomized controlled trials for perioperative surgical thromboprophylaxis. However, the results from these studies are inconsistent in terms of efficacy and safety to reach a clinical decision. The objective of this study was to systematically review the randomized controlled trials comparing the efficacy and safety of fondaparinux and LMWH for perioperative surgical thromboprophylaxis. Methods and Results Systematic search in various databases was done to identify randomized controlled trials comparing fondaparinux and LMWH published during the years 2000 to 2017. Outcomes of interest in this study included venous thromboembolism up to day 15, all-cause mortality up to day 90, major bleeding, and minor bleeding during the treatment period. Analyses were performed with the relative odds based on a random-effects model using Mantel-Haenszel statistics. Results were presented as odds ratios with their 95% CIs. The assessment of study quality was performed as per Cochrane collaboration. After screening 10 644 articles, 12 randomized controlled trials including 14 906 patients were included in the final analyses. Pooled analyses showed the odds of venous thromboembolism in the fondaparinux group were 0.49 times the odds in LMWH group ( OR =0.49 [0.38-0.64]). However, the odds of major bleeding in the fondaparinux group were 1.48 times the odds in the LMWH group ( OR =1.48 [1.15-1.90]). Conclusions Fondaparinux was associated with a superior efficacy in terms of reduction of venous thromboembolism in this meta-analysis. However, it was also associated with increased odds of major bleeding.

Topics: Adult; Aged; Aged, 80 and over; Drug Administration Schedule; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Preoperative Care; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Surgical Procedures, Operative; Time Factors; Treatment Outcome; Venous Thromboembolism

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

Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE.. To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in people with cancer.. A comprehensive search included a major electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) (2018, Issue 1), MEDLINE (via Ovid) and Embase (via Ovid); handsearching of conference proceedings; checking of references of included studies; use of the 'related citation' feature in PubMed; and a search for ongoing studies. This update of the systematic review was based on the findings of a literature search conducted on 14 January 2018.. Randomized controlled trials (RCTs) assessing the benefits and harms of LMWH, UFH, and fondaparinux in people with cancer and objectively confirmed VTE.. Using a standardized form, we extracted data in duplicate on study design, participants, interventions outcomes of interest, and risk of bias. Outcomes of interested included all-cause mortality, symptomatic VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia. We assessed the certainty of evidence for each outcome using the GRADE approach.. Of 15440 identified citations, 7387 unique citations, 15 RCTs fulfilled the eligibility criteria. These trials enrolled 1615 participants with cancer and VTE: 13 compared LMWH with UFH enrolling 1025 participants, one compared fondaparinux with UFH and LMWH enrolling 477 participants, and one compared dalteparin with tinzaparin enrolling 113 participants. The meta-analysis of mortality at three months included 418 participants from five studies and that of recurrent VTE included 422 participants from 3 studies. The findings showed that LMWH likely decreases mortality at three months compared to UFH (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.40 to 1.10; risk difference (RD) 57 fewer per 1000, 95% CI 101 fewer to 17 more; moderate certainty evidence), but did not rule out a clinically significant increase or decrease in VTE recurrence (RR 0.69, 95% CI 0.27 to 1.76; RD 30 fewer per 1000, 95% CI 70 fewer to 73 more; moderate certainty evidence).The study comparing fondaparinux with heparin (UFH or LMWH) did not exclude a beneficial or detrimental effect of fondaparinux on mortality at three months (RR 1.25, 95% CI 0.86 to 1.81; RD 43 more per 1000, 95% CI 24 fewer to 139 more; moderate certainty evidence), recurrent VTE (RR 0.93, 95% CI 0.56 to 1.54; RD 8 fewer per 1000, 95% CI 52 fewer to 63 more; moderate certainty evidence), major bleeding (RR 0.82, 95% CI 0.40 to 1.66; RD 12 fewer per 1000, 95% CI 40 fewer to 44 more; moderate certainty evidence), or minor bleeding (RR 1.53, 95% CI 0.88 to 2.66; RD 42 more per 1000, 95% CI 10 fewer to 132 more; moderate certainty evidence)The study comparing dalteparin with tinzaparin did not exclude a beneficial or detrimental effect of dalteparin on mortality (RR 0.86, 95% CI 0.43 to 1.73; RD 33 fewer per 1000, 95% CI 135 fewer to 173 more; low certainty evidence), recurrent VTE (RR 0.44, 95% CI 0.09 to 2.16; RD 47 fewer per 1000, 95% CI 77 fewer to 98 more; low certainty evidence), major bleeding (RR 2.19, 95% CI 0.20 to 23.42; RD 20 more per 1000, 95% CI 14 fewer to 380 more; low certainty evidence), or minor bleeding (RR 0.82, 95% CI 0.30 to 2.21; RD 24 fewer per 1000, 95% CI 95 fewer to 164 more; low certainty evidence).. LMWH is possibly superior to UFH in the initial treatment of VTE in people with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review. The decision for a person with cancer to start LMWH therapy should balance the benefits and harms and consider the person's values and preferences.

Topics: Anticoagulants; Dalteparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Polysaccharides; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Tinzaparin; Venous Thromboembolism

The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is the third update of a review first published in 2007.. To assess the efficacy and safety of topical, medical, and surgical treatments for ST of the leg in improving local symptoms and decreasing thromboembolic complications.. For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (March 2017), CENTRAL (2017, Issue 2), and trials registries (March 2017). We handsearched the reference lists of relevant papers and conference proceedings.. Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the legs that included people with a clinical diagnosis of ST of the legs or objective diagnosis of a thrombus in a superficial vein.. Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus. We assessed the quality of the evidence using the GRADE approach.. We identified three additional trials (613 participants), therefore this update considered 33 studies involving 7296 people with ST of the legs. Treatment included fondaparinux; rivaroxaban; low molecular weight heparin (LMWH); unfractionated heparin (UFH); non-steroidal anti-inflammatory drugs (NSAIDs); compression stockings; and topical, intramuscular, or intravenous treatment to surgical interventions such as thrombectomy or ligation. Only a minority of trials compared treatment with placebo rather than an alternative treatment and many studies were small and of poor quality. Pooling of the data was possible for few outcomes, and none were part of a placebo-controlled trial. In one large, placebo-controlled RCT of 3002 participants, subcutaneous fondaparinux was associated with a significant reduction in symptomatic VTE (risk ratio (RR) 0.15, 95% confidence interval (CI) 0.04 to 0.50; moderate-quality evidence), ST extension (RR 0.08, 95% CI 0.03 to 0.22; moderate-quality evidence), and ST recurrence (RR 0.21, 95% CI 0.08 to 0.54; moderate-quality evidence) relative to placebo. Major bleeding was infrequent in both groups with very wide CIs around risk estimate (RR 0.99, 95% CI 0.06 to 15.86; moderate-quality evidence). In one RCT on 472 high-risk participants with ST, fondaparinux was associated with a non-significant reduction of symptomatic VTE compared to rivaroxaban 10 mg (RR 0.33, 95% CI 0.03 to 3.18; low-quality evidence). There were no major bleeding events in either group (low-quality evidence). In another placebo-controlled trial, both prophylactic and therapeutic doses of LMWH (prophylactic: RR 0.44, 95% CI 0.26 to 0.74; therapeutic: RR 0.46, 95% CI 0.27 to 0.77) and NSAIDs (RR 0.46, 95% CI 0.27 to 0.78) reduced the extension (low-quality evidence) and recurrence of ST (low-quality evidence) in comparison to placebo, with no significant effects on symptomatic VTE (low-quality evidence) or major bleeding (low-quality evidence). Overall, topical treatments improved local symptoms compared with placebo, but no data were provided on the effects on VTE and ST extension. Surgical treatment combined with elastic stockings was associated with a lower VTE rate and ST progression compared with elastic stockings alone. However, the majority of studies that compared different oral treatments, topical treatments, or surgery did not report VTE, ST progression, adverse events, or treatment adverse effects.. Prophylactic dose fondaparinux given for 45 days appears to be a valid therapeutic option for ST of the legs for most people. The evidence on topical treatment or surgery is too limited and does not inform clinical practice about the effects of these treatments in terms of VTE. Further research is needed to assess the role of rivaroxaban and other direct oral factor-X or thrombin inhibitors, LMWH, and NSAIDs; the optimal doses and duration of treatment in people at various risk of recurrence; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Factor Xa Inhibitors; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Rivaroxaban; Stockings, Compression; Thrombectomy; Thromboembolism; Thrombophlebitis; Venous Thromboembolism

Venous thromboembolism (VTE) is a major global cause of morbidity and mortality. Low molecular weight heparin (LMWH) and fondaparinux (FDP) are frequently used to treat and prevent VTE and have a variety of safety and practical advantages over other anticoagulants, including use in outpatient settings. These medications are commonly listed on drug formularies, which act as a gateway for health plan prescription coverage by outlining the circumstances under which patients will be covered for specific drugs and drug products. Because patient access to medications is impacted by the nature of their listing on formularies, they must be rigorously reviewed and modernized as new evidence emerges.. As part of a broader drug class review team, we completed a systematic review of clinical practice guidelines to determine whether the recommendations they reported aligned with the indications listed for the coverage of LMWH and FDP in an outpatient drug formulary. Guideline quality was assessed using the Appraisal of Guidelines for Research & Evaluation (AGREE) II tool. Recommendation matrices were used to systematically compare, categorize, and summarize included recommendations.. Twenty-seven guidelines were included from which 168 eligible recommendations were identified. Generally, AGREE II domains were adequately addressed; however, domain five (applicability) was poorly addressed. Most recommendations were based on moderate- to low-quality/limited evidence and reported on the use of LMWHs generally; few reported on specific agents.. Our findings contributed to the recommendation that the formulary listing for LMWH and FDP be streamlined to include coverage for specific outpatient indications. The paucity of available evidence on the comparative efficacy of specific LMWH agents against each other and FDP limited agent-specific listing recommendations, highlighting the need for high-quality comparative studies on this topic.

Topics: Decision Making; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Practice Guidelines as Topic; Venous Thromboembolism

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

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

Venous thromboembolism (VTE) is a common and potentially fatal complication of arthroplasty.. We reviewed randomized trials to determine which anticoagulant has the best safety and efficacy in hip and knee arthroplasty patients. We searched PubMed, MEDLINE, and EMBASE through January 2016.. Compared to enoxaparin (most commonly dosed 40 mg once daily), the relative risk (RR) of VTE was lowest for edoxaban 30 mg once daily (0.49; 95% confidence interval [CI], 0.32-0.75), fondaparinux 2.5 mg once daily (0.53; 95% CI, 0.45-0.63), and rivaroxaban 10 mg once daily (0.55; 95% CI, 0.46-0.66), and highest for dabigatran 150 mg once daily (1.19; 95% CI; 0.98-1.44). The RR of major/clinically relevant bleeding was lowest for apixaban 2.5 mg twice daily (0.84; 95% CI; 0.70-0.99) and highest for rivaroxaban (1.27; 95% CI, 1.01-1.59) and fondaparinux (1.64; 95% CI, 0.24-11.35). Fondaparinux was the only agent that was more effective than enoxaparin 30 mg twice daily (VTE RR = 0.58; 95% CI, 0.43-0.76).. With the possible exception of apixaban, newer anticoagulants that lower the risk of postoperative VTE increase bleeding.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Dabigatran; Enoxaparin; Fondaparinux; Hemorrhage; Humans; Morpholines; Polysaccharides; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

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

Trousseau's syndrome (cancer-associated thrombosis) is the second leading cause of death in cancer patients, after death from cancer itself. The risk of a venous thromboembolism is 4- to 7-fold higher in patients with cancer than in those without cancer. The causes of this impaired coagulation are associated with general patient-related risk factors, and other factors that are specific to the particular cancer or treatment. It is important to assess the risk of thrombotic events in cancer patients and administer effective prophylaxis and treatment. Effective prophylaxis and treatment of venous thromboembolism reduces morbidity and mortality, and improves patients' quality of life. Low molecular weight heparin is the first-line treatment for venous thromboembolism, as an effective and safe means for prophylaxis and treatment, according to guidelines released by international scientific societies. Oral anticoagulation therapy with warfarin is preferable to no therapy. However, warfarin has low efficacy and is associated with high rates of recurrence. If low molecular weight heparin is unavailable, some guidelines recommend the use of vitamin K antagonists that have a target international normalized ratio in the range of 2-3, as acceptable alternatives. Novel oral anticoagulants that directly inhibit factor Xa or thrombin are promising for the prophylaxis of high-risk cancer patients and in the long-term treatment of venous thromboembolism. However, to date, there is insufficient evidence to support the use of these new anticoagulants.

Topics: Administration, Oral; Anticoagulants; Asian; Black or African American; Disease Management; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Neoplasms; Polysaccharides; Prevalence; Quality of Life; Recurrence; Risk Factors; Taiwan; Thrombosis; United States; Venous Thromboembolism; Vitamin K; Warfarin; White People

Despite widespread diffusion of pharmacological prophylaxis, deep venous thrombosis (DVT) is still a common cause of morbidity after major orthopedic surgery (total hip replacement--THR--and total knee replacement--TKR). At present, clear evidence has been provided that pharmacological primary prophylaxis with low molecular weight heparin (LMWH) is associated with a significant decrease in the incidence of venous thromboembolism. The main limitation of LMWH prophylaxis however is the need for parenteral administration with a not negligible drop-out of treatment. Newer oral anticoagulants (NAOs) dabigatran, rivaroxaban, apixiban and edoxaban may be valid alternatives in elective surgery. Several studies have demonstrated the efficacy and safety of NAOs after THR and TKR. The research for new compounds and their antidote is under continuous development Aim of this paper was to review the indications and clinical results of DVT prophylaxis with NAO in patients undergoing major orthopaedic surgery.

Topics: Administration, Oral; Anticoagulants; Dabigatran; Enoxaparin; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Orthopedic Procedures; Polysaccharides; Rivaroxaban; Venous Thromboembolism

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

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 occurrence of pediatric venous thromboembolism (VTE) and the associated sequelae are increasing. The purpose of this PubMed-based review was to summarize the evidence published between 1 August 2014 and 31 March 2015 regarding pediatric VTE epidemiology, risk factors and risk scores, as well as the results from clinical prevention and treatment studies in children. We also sought to provide an update regarding ongoing clinical trials in pediatric VTE prevention and treatment, based on a recent (31 March 2015) search of the clinicaltrials.gov and EudraCT clinical trial registration databases.. Recent research has defined and/or substantiated risk factors and risk models for pediatric VTE. Studies of pharmacokinetics/pharmacodynamics and safety/efficacy of fondaparinux and dalteparin have also been reported, in addition to findings of the pilot/feasibility phase of a randomized controlled trial on duration of anticoagulation. With regard to oral direct anticoagulants, to date 14 pediatric clinical trials have been registered on clinicaltrials.gov and EudraCT, some of which represent US/North American instances of trials previously launched in Europe.. The present findings on published studies and registered trials in pediatric VTE mark an ongoing period of remarkable activity and advancement in the field of pediatric VTE.

Topics: Anticoagulants; Child; Chronic Disease; Clinical Trials as Topic; Dalteparin; Fibrinolytic Agents; Fondaparinux; Humans; Incidence; Polysaccharides; Risk Factors; Venous Thromboembolism

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

Heparin, one of the common anticoagulants, is clinically used to prevent and treat venous thromboembolism (VTE). Though it has been the drug of choice for many advanced medical and surgical procedures with a long history, the adverse events, such as bleeding, heparin-induced thrombocytopenia (HIT), allergic reactions, follow. Therefore, low molecular weight heparins (LMWHs) and ultra low molecular weight heparins (ULMWHs), with lower molecular weights, higher anti-FXa activity, longer half-life times and lower incidence of adverse events than unfractionated heparin (UFH), were researched and developed. Fondaparinux, a chemically synthesized ULMWH of pentasaccharide, has the same antithrombin III (AT-III)-binding sequence as found in UFH and LMWH. In addition, AVE5026 and RO-14, another two ULMWHs, are obtained by selective chemical depolymerization. In this paper, we review the preparation process, pharmacological effects and clinical applications of fondaparinux, AVE5026 and RO-14.

Topics: Animals; Anticoagulants; Blood Coagulation; Drug Design; Factor Xa; Factor Xa Inhibitors; Fondaparinux; Half-Life; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Molecular Structure; Molecular Weight; Polysaccharides; Structure-Activity Relationship; Venous Thromboembolism

Pregnancy is a specific state of heightened coagulability related to the increase in procoagulant agents and to the reduced fibrinolysis. Pregnancy is associated with a 4-fold increased risk of developing venous thromboembolism (VTE) and this risk still increases to 14-fold during puerperium. A correlation between the metabolic syndrome and development of cardiovascular events and cerebrovascular incidents has been described. Such a relationship is referred to a hypercoagulable state due to increased serum levels of the plasminogen activator inhibitor-1 (PAI-1), fibrinogen, factor (F) VII and VIII, von Willebrand factor and from endothelial activation, caused by increased circulating adhesion molecules. As to the risk of VTE, the probability for its association with cardiovascular incidents is increased by common underlying mechanisms such as the activation of platelets and the blood coagulation. A correlation between idiopathic VTE and the metabolic syndrome has been reported. The anticoagulant therapy may be recommended during the pregnancy for the treatment or the prophylaxis of VTE and, in women with artificial heart valves, for the prevention of the valve thrombosis and systemic embolisation. There are also specific conditions during pregnancy which benefit from anticoagulant use, such as recurrent fetal loss, thrombophilia and assisted reproductive technology. There are no published specific data about using of anticoagulant agents in pregnant patients with the metabolic syndrome except for a few articles addressing reproductive problems. The mechanisms of anticoagulant action were studied with the focus on heparinoids, because of their safety not only for the patient but also for the fetus. The new oral anticoagulants were also shortly described although they have been contraindicated during the pregnancy.

Topics: Animals; Anticoagulants; Aspirin; Female; Fondaparinux; Heparin; Humans; Metabolic Syndrome; Polysaccharides; Pregnancy; Venous Thromboembolism; Warfarin

Compared with patients without cancer, patients with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE.. To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in patients with cancer.. A comprehensive search for studies of anticoagulation in patients with cancer including a February 2013 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and ISI Web of Science.. Randomized clinical trials (RCTs) comparing LMWH, UFH, and fondaparinux in patients with cancer and objectively confirmed VTE.. Using a standardized data form, review authors extracted data in duplicate on methodologic quality, participants, interventions, and outcomes of interest that included mortality, recurrent VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia.. Of 9559 identified citations, 16 RCTs were eligible: 13 compared LMWH with UFH, two compared fondaparinux with heparin, and one compared dalteparin with tinzaparin. Meta-analysis of 11 studies showed a statistically significant reduction in mortality at three months of follow-up with LMWH compared with UFH (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.52 to 0.98). There was little change in the effect estimate after excluding studies of lower methodologic quality (RR 0.72; 95% CI 0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH showed no statistically significant reduction in VTE recurrence (RR 0.78; 95% CI 0.29 to 2.08). The overall quality of evidence was low for LMWH versus UFH due to imprecision and likely publication bias. There were no statistically significant differences between heparin and fondaparinux for the outcomes of mortality (RR 1.27; 95% CI 0.88 to 1.84), recurrent VTE (RR 0.95; 95% CI 0.57 to 1.60), major bleeding (RR 0.79; 95% CI 0.39 to1.63), or minor bleeding (RR 1.50; 95% CI 0.87 to 2.59). The one study comparing dalteparin with tinzaparin found no statistically significant difference in mortality (RR 0.86; 95% CI 0.43 to 1.73).. LMWH is possibly superior to UFH in the initial treatment of VTE in patients with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review.

Topics: Anticoagulants; Dalteparin; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Polysaccharides; Randomized Controlled Trials as Topic; Secondary Prevention; Tinzaparin; Venous Thromboembolism

Before the advent of oral, targeted anticoagulants, physicians had no choice regarding the type of oral anticoagulant prescribed, as every patient received warfarin. The new oral direct thrombin and factor Xa inhibitors give the prescribing physician, as well as the patient, greater choice. Variation in dosing, half-life, elimination, monitoring, and reversal will help the clinician decide on the appropriate anticoagulant for the appropriate patient. Rather than replace warfarin, each anticoagulant will now have a particular niche, and the decision of which agent to prescribe will be determined at the bedside.

Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Drug Monitoring; Factor Xa Inhibitors; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Medication Adherence; Orthopedic Procedures; Partial Thromboplastin Time; Polysaccharides; Randomized Controlled Trials as Topic; Venous Thromboembolism; Vitamin K; Warfarin

To systematically review the efficacy and safety of fondaparinux and enoxaparin in the prevention of venous thromboembolism (VTE) after major orthopedic surgery.. The MEDLINE, EMbase, the Cochrane Library, CNKI, CBM, VIP and Wanfang databases (from their establishment to October, 2012) were searched for randomized controlled trials (RCTs) comparing the effects of fondaparinux and enoxaparin in preventing VTE after major orthopedic surgery. The related journals and conference papers were manually searched. The outcome measurements were the incidence of total VTE, deep venous thrombosis (DVT), symptomatic VTE, pulmonary embolism (PE), major bleeding and any other adverse event. The quality of literatures was evaluated and the data were extracted for meta-analysis.. Five RCTs involving 7611 patients were included pertaining to major knee surgery (1 RCT), hip fracture surgery (2 RCTs) and total hip arthroplasty (3 RCTs). The incidences of total VTE and DVT were significantly lower in fondaparinux group than in enoxaparin group [RR=0.52, 95%CI (0.40,0.67), P<0.00001; RR=0.49, 95%CI (0.42, 0.58), P<0.00001]. The incidence of symptomatic VTE was similar between the two groups [RR=1.52, 95%CI (0.80,2.88), P=0.20]. Fondaparinux was associated with a significantly increased incidence of major bleeding compared to enoxaparin group [RR=1.55, 95%CI (1.14,2.12), P=0.006], but the mortality rates were comparable between the two groups [RR=0.93, 95%CI (0.63,1.37), P=0.72].. Compared with enoxaparin, fondaparinux can reduce the risk of postoperative VTE and do not increase the mortality rate following major orthopedic surgery though with an increased risk of major bleeding.

Topics: Enoxaparin; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Randomized Controlled Trials as Topic; Treatment Outcome; Venous Thromboembolism

The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is the second update of a review first published in 2007.. To assess the efficacy and safety of topical, medical, and surgical treatments in patients presenting with ST of the legs.. For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched November 2012) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11). We handsearched the reference lists of relevant papers and conference proceedings.. Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the legs that included participants with a clinical diagnosis of ST of the legs or an objective diagnosis of a thrombus in a superficial vein.. Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus.. We identified four additional trials (986 patients), so this update considered 30 studies involving 6507 participants with ST of the legs.Treatment ranged from fondaparinux, low molecular weight heparin (LMWH), unfractionated heparin (UFH), non-steroidal anti-inflammatory agents (NSAIDs), topical treatment, oral treatment, intramuscular treatment, and intravenous treatment to surgery. Only a minority of trials compared treatment with placebo rather than an alternative treatment, none evaluated the same treatment comparisons on the same study outcomes (which precluded meta-analysis), and many of the studies were small and of poor quality. In one large, placebo-controlled RCT of about 3000 patients, subcutaneous fondaparinux was associated with a significant reduction in symptomatic VTE (RR 0.15; 95% CI 0.04 to 0.50), ST extension (RR 0.08; 95% CI 0.03 to 0.22), and ST recurrence (RR 0.21; 95% CI 0.08 to 0.54) with comparable rates of major bleeding (RR 0.99; 95% CI 0.06 to 15.86) relative to placebo. In a further placebo-controlled trial, both prophylactic and therapeutic doses of LMWH (RR 0.40; 95% CI 0.22 to 0.72 and RR 0.42; 95% CI 0.23 to 0.75, respectively) and NSAIDs (RR 0.41; 95% CI 0.23 to 0.75) reduced the extension and recurrence of ST in comparison to placebo, with no significant effects on symptomatic VTE nor major bleeding. Overall, topical treatments improved local symptoms compared with placebo but no data were provided on the effects on VTE and ST extension. Surgical treatment combined with elastic stockings was associated with a lower VTE rate and ST progression compared with elastic stockings alone. However, the majority of studies that compared different oral treatment, topical treatment, or surgery did not report VTE, ST progression, adverse events, or treatment side effects.. Prophylactic dose fondaparinux given for six weeks appears to be a valid therapeutic option for ST of the legs. The evidence on oral treatments, topical treatment, or surgery is too limited and does not inform clinical practice about the effects of these treatments in terms of VTE and ST progression. Further research is needed to assess the role of the new oral direct thrombin and activated factor-X inhibitors, LMWH, and NSAIDs; the optimal doses and duration of treatment; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Thromboembolism; Thrombophlebitis; Venous Thromboembolism

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

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

The efficacy and safety of heparin and low-molecular-weight heparins (LMWHs) are well documented in venous and arterial thromboembolism. Several drawbacks of heparins have inspired the development of newer parenteral anticoagulants for specific indications, including heparin-induced thrombocytopenia (HIT) and percutaneous coronary interventions (PCI). The direct thrombin inhibitors recombinant hirudin and argatroban are now established alternatives for HIT patients, and bivalirudin is one of the most used anticoagulants in PCI. The pentasaccharide fondaparinux is an alternative for LMWH for thromboprophylaxis in various clinical settings and for patients with an acute coronary syndrome (ACS) not scheduled for PCI. In Europe, it was recently approved for treatment of superficial vein thrombosis. Further development of new parenteral anticoagulants is slow and the emphasis has shifted towards development of new oral anticoagulants and antiplatelet drugs. Still, promising new anticoagulants, some targeting less conventional targets in the coagulation system, have been developed and will undergo further clinical evaluation.

Topics: Acute Coronary Syndrome; Antithrombins; Arginine; Fondaparinux; Hirudin Therapy; Hirudins; Humans; Infusions, Parenteral; Peptide Fragments; Percutaneous Coronary Intervention; Pipecolic Acids; Polysaccharides; Randomized Controlled Trials as Topic; Recombinant Proteins; Sulfonamides; Thrombin; Venous Thromboembolism

Venous thromboembolism (VTE) is a frequent complication among acutely ill medical patients hospitalized for congestive heart failure, acute respiratory insufficiency, rheumatologic disorders, and acute infectious and/or inflammatory diseases. Based on robust data from randomized controlled studies and meta-analyses showing a reduced incidence of VTE by 40% to about 60% with pharmacologic thromboprophylaxis, prevention of VTE with low molecular weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux is currently recommended in all at-risk hospitalized acutely ill medical patients. In patients who are bleeding or are at high risk for major bleeding, mechanical prophylaxis with graduated compression stockings or intermittent pneumatic compression may be suggested. Thromboprophylaxis is generally continued for 6 to 14 days or for the duration of hospitalization. Selected cases could benefit from extended thromboprophylaxis beyond this period, although the risk of major bleeding remains a concern, and additional studies are needed to identify patients who may benefit from prolonged prophylaxis. For hospitalized acutely ill medical patients with renal insufficiency, a low dose (1.5 mg once daily) of fondaparinux or prophylactic LMWH subcutaneously appears to have a safe profile, although proper evaluation in randomized studies is lacking. The evidence on the use of prophylaxis for VTE in this latter group of patients, as well as in those at higher risk of bleeding complications, such as patients with thrombocytopenia, remains scarce. For critically ill patients hospitalized in intensive care units with no contraindications, LMWH or UFH are recommended, with frequent and careful assessment of the risk of bleeding. In this review, we discuss the evidence for use of thromboprophylaxis for VTE in acutely ill hospitalized medical patients, with a focus on (low-dose) fondaparinux.

Topics: Anticoagulants; Critical Illness; Dose-Response Relationship, Drug; Fondaparinux; Hemorrhage; Hospitalization; Humans; Intensive Care Units; Polysaccharides; Randomized Controlled Trials as Topic; Risk Factors; Venous Thromboembolism

Deep venous thrombosis (DVT) is a common cause of morbidity after orthopedic surgery, both in the early post operative period when pulmonary embolism may complicate in hospital clinical course or occur after discharge and later due to development of post thrombotic syndrome. At present, clear evidence has been provided that pharmacological primary prophylaxis of venous thromboembolism (VTE) is associated with an impressive decrease in the incidence of DVT and related complications. The main limitation of VTE prophylaxis with anticoagulant drug is the risk of bleeding. Both pharmacological and non pharmacological measures are available and indication, clinical results and limitations will be discussed for each. For drug prophylaxis at present mainly are used as parenteral agents, low dose un fractionated heparin, low molecular weight heparin and fondaparinux; however, limited compliance may be a concern. Newer oral anticoagulants, dabigatran, rivaroxaban and apixiban, may be indicated in elective surgery in particular in patients with expected poor adherence to parenteral route. Non pharmacological treatment includes measures directed to decrease the effects of blood stasis, intermittent pneumatic compression device (IPCD) and graduated compression stockings, mechanical devices, inferior caval vein filters. Aim of the present review was to suggest practical approach to DVT prophylaxis in patients undergoing major orthopedic surgery.

Topics: Anticoagulants; Chemistry, Pharmaceutical; Fondaparinux; Heparin; Humans; Orthopedic Procedures; Polysaccharides; Venous Thromboembolism

Despite evidence-based guidelines for venous thromboembolism prevention, substantial variability is found in practice. Many economic evaluations of new drugs for thromboembolism prevention do not occur prospectively with efficacy studies and are sponsored by the manufacturers, raising the possibility of bias. We performed a systematic review of economic analyses of venous thromboembolism prevention in hospitalized patients to inform clinicians and policy makers about cost-effectiveness and the potential influence of sponsorship.. We searched MEDLINE, EMBASE, Cochrane Databases, ACP Journal Club, and Database of Abstracts of Reviews of Effects, from 1946 to September 2011. We extracted data on study characteristics, quality, costs, and efficacy.. From 5,180 identified studies, 39 met eligibility and quality criteria. Each addressed pharmacologic prevention: low-molecular-weight heparins versus placebo (five), unfractionated heparin (12), warfarin (eight), one or another agents (five); fondaparinux versus enoxaparin (11); and rivaroxaban and dabigatran versus enoxaparin (two). Low-molecular-weight heparins were most economically attractive among most medical and surgical patients, whereas fondaparinux was favored for orthopedic patients. Fondaparinux was associated with increased bleeding events. Newer agents rivaroxaban and dabigatran may offer additional value. Of all economic evaluations, 64% were supported by manufacturers of a "new" agent. The new agent had a favorable outcome in 38 (97.4%) of 39 evaluations [95% confidence interval [CI] (86.5 to 99.9)]. Among studies supported by a pharmaceutical company, the sponsored medication was economically attractive in 24 (96.0%) of 25 [95% CI, 80.0 to 99.9)]. We could not detect a consistent bias in outcome based on sponsorship; however, only a minority of studies were unsponsored.. Low-molecular-weight heparins and fondaparinux are the most economically attractive drugs for venous thromboembolism prevention in hospitalized patients. Approximately two thirds of evaluations were supported by the manufacturer of the new agent; such drugs were likely to be reported as economically favorable.

Topics: Anticoagulants; Cost-Benefit Analysis; Enoxaparin; Fondaparinux; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Polysaccharides; Practice Guidelines as Topic; Venous Thromboembolism

The use of anticoagulants for the prevention of venous thromboembolism (VTE) in hospitalized medical and surgical oncology patients is discussed.. Hospitalized patients are often at risk for developing VTE, and risk is increased in patients who have cancer. Moreover, the incidence of VTE appears to be rising in hospitalized cancer patients, who have a 2.2-fold increased risk of mortality with a VTE compared with similar patients without VTE. The literature indicates that these patients are often inadequately anticoagulated, despite strong recommendations for prophylaxis. Although there are few studies that specifically address VTE prophylaxis in cancer patients, there are several large trials that have examined data in cancer subgroups. The trials have directly compared low-molecular-weight heparin (LMWH) with placebo, unfractionated heparin with LMWH, factor Xa inhibitor (fondaparinux) with placebo, and fondaparinux with LMWH. Three important guidelines provide current recommendations for VTE prophylaxis; the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the American College of Chest Physicians (ACCP) recommend unfractionated heparin, LMWH, or fondaparinux for VTE prophylaxis when there are no contraindications. Pharmacists can play an essential role in ensuring that VTE prophylaxis is appropriate for individual patients. Interventions to improve compliance with guidelines are particularly important now due to financial incentives from quality-focused organizations whose mandate is to decrease preventable mortality events in hospitals.. Hospitalized patients with cancer often do not receive appropriate thromboprophylaxis. Guidelines from ASCO, ACCP, and NCCN recommend unfractionated heparin, an LMWH, or fondaparinux for VTE prophylaxis when there are no contraindications to such therapy.

Topics: Anticoagulants; Fondaparinux; Guideline Adherence; Heparin; Hospitalization; Humans; Neoplasms; Pharmacists; Pharmacy Service, Hospital; Polysaccharides; Practice Guidelines as Topic; Professional Role; Venous Thromboembolism

The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is an update of a review first published in 2007.. To assess the efficacy and safety of topical, medical, and surgical treatments in patients presenting with ST of the legs.. For this update the Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched 29 November 2011) and CENTRAL (2011, Issue 4). We handsearched reference lists of relevant papers and conference proceedings.. Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the leg that included participants with a clinical diagnosis of ST of the legs or objective diagnosis of a thrombus in the superficial vein.. Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus.. Twenty-six studies involving 5521 participants with ST of the legs were included in this review. The methodological quality of most of the trials was poor. Treatment ranged from fondaparinux, low molecular weight heparin (LMWH), unfractionated heparin (UFH), non-steroidal anti-inflammatory agents (NSAIDs), topical treatment, oral treatment, intramuscular treatment, and intravenous treatment to surgery. In a placebo-controlled RCT of about 3000 patients, fondaparinux was associated with a significant reduction in symptomatic VTE (RR 0.15; 95% CI 0.04 to 0.50), extension (RR 0.08; 95% CI 0.03 to 0.22), and recurrence of ST (RR 0.21; 95% CI 0.08 to 0.54) with comparable rates of major bleeding (RR 0.99; 95% CI 0.06 to 15.86) relative to placebo. Both prophylactic and therapeutic doses of LMWH (RR 0.40; 95% CI 0.22 to 0.72 and RR 0.42; 95% CI 0.23 to 0.75, respectively) and NSAIDs (RR 0.41; 95% CI 0.23 to 0.75) reduced the extension and recurrence of ST in comparison to placebo, with no significant effects on symptomatic VTE nor major bleeding. Overall, topical treatments improved local symptoms. However, no data were provided on the effects of these treatments on VTE and ST extension. Surgical treatment combined with elastic stockings in ST was associated with a lower VTE rate and ST progression compared with elastic stockings alone.. Prophylactic dose fondaparinux given for six weeks appears to be a valid therapeutic option for ST of the legs. Further research is needed to assess the role of new oral direct thrombin and activated factor-X inhibitors, LMWH, NSAIDs; the optimal doses and duration of treatment; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Thrombophlebitis; Venous Thromboembolism

Compared to patients without cancer, patients with cancer who receive anticoagulant treatment for venous thromboembolism are more likely to develop recurrent venous thromboembolism (VTE).. To compare the efficacy and safety of three types of parenteral anticoagulants for the initial treatment of VTE in patients with cancer.. A comprehensive search for studies of anticoagulation in cancer patients including a February 2010 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI Web of Science.. Randomized clinical trials (RCTs) comparing low molecular weight heparin (LMWH), unfractionated heparin (UFH), and fondaparinux in patients with cancer and objectively confirmed VTE.. Using a standardized data form, data was extracted in duplicate on methodological quality, participants, interventions, and outcomes of interest that included mortality, recurrent VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia.. Of 3986 identified citations, 16 RCTs were eligible: 13 compared LMWH to UFH, two compared fondaparinux to heparin, and one compared dalteparin to tinzaparin. Meta-analysis of 11 studies showed a statistically significant reduction in mortality at three months of follow up with LMWH compared with UFH (relative risk (RR) 0.71; 95% confidence interval (CI) 0.52 to 0.98). There was little change in the effect estimate after excluding studies of lower methodological quality (RR 0.72; 95% CI 0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH showed no statistically significant reduction in VTE recurrence (RR 0.78; 95% CI 0.29 to 2.08). The overall quality of evidence was low for LMWH versus UFH due to imprecision and likely publication bias. There were no statistically significant differences between heparin and fondaparinux for the outcomes of death (RR 1.27; 95% CI 0.88 to 1.84), recurrent VTE (RR 0.95; 95% CI 0.57 to 1.60), major bleeding (RR 0.79; 95% CI 0.39 to1.63) or minor bleeding (RR 1.50; 95% CI 0.87 to 2.59). The one study comparing dalteparin to tinzaparin did not find a statistically significant difference in mortality (RR 0.86; 95% CI 0.43 to 1.73).. LMWH is possibly superior to UFH in the initial treatment of VTE in patients with cancer. Additional trials focusing on patient important outcomes will further inform the questions addressed in this review.

Topics: Anticoagulants; Dalteparin; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Polysaccharides; Randomized Controlled Trials as Topic; Tinzaparin; Venous Thromboembolism

Venous thrombosis and pulmonary embolism rarely occur in children but are associated with significant morbidity and mortality. Venous thromboembolism (VTE) mostly affects children with severe underlying conditions and multiple risk factors. Newborns and adolescents are at the highest risk. Standard and low molecular weight heparins and vitamin K antagonists are routinely used for the prevention and treatment of VTE. The new anticoagulants, both parenteral such as argatroban, bivalirudin and fondaparinux and oral such as dabigatran and rivaroxaban, have favourable pharmacological properties, all are approved for clinical use in adults and are currently being investigated in children. Argatroban is the only new anticoagulant licensed for use in children so far. The role of these new anticoagulants as alternative anticoagulants for children remains to be defined. This review focuses on the characteristics of VTE in children and reviews current knowledge on the use of the new thrombin and factor Xa inhibitors in this population.

Topics: Adolescent; Anticoagulants; Arginine; Benzimidazoles; beta-Alanine; Child; Child, Preschool; Dabigatran; Drug Approval; Factor Xa Inhibitors; Fondaparinux; Hirudins; Humans; Infant; Infant, Newborn; Morpholines; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Risk Factors; Rivaroxaban; Sulfonamides; Thiophenes; Thrombin; Venous Thromboembolism

The use of antithrombotic drugs for the prevention of venous thromboembolism (VTE) in patients undergoing surgery is presently based on solid principles and high-level scientific evidence. This article reviews current strategies of pharmacological thromboprophylaxis. The level of VTE risk following surgery depends on a variety of factors that the surgeon should take into account, including the type of surgery and the presence of additional risk factors, such as elderly age and cancer. In patients undergoing minor general surgery, early mobilization is sufficient as prophylaxis, whereas in those undergoing major general surgery, thromboprophylaxis with low molecular weight heparin (LMWH), low-dose unfractionated heparin, or the pentasaccharide fondaparinux is recommended. Patients undergoing major orthopedic surgery have a particularly high risk of VTE, and routine thromboprophylaxis with LMWH, fondaparinux, or a vitamin K antagonist (international normalized ratio target: 2.0 to 3.0) is the standard of care in this group of patients. Recently, two new oral anticoagulants, rivaroxaban (a factor Xa inhibitor) and dabigatran etexilate (a direct thrombin inhibitor) have been licensed to be used for thromboprophylaxis after orthopedic surgery in Europe. Mechanical methods of thromboprophylaxis (compression stockings, intermittent pneumatic compression, vena cava filters), not discussed in detail in this review, should always be considered in patients at high thrombotic risk, in association with the pharmacological strategies, or in cases of contraindications to anticoagulants, as in patients or procedures at high risk of bleeding.

Topics: Aged; Anticoagulants; Antithrombins; Arthroscopy; Bariatric Surgery; Benzimidazoles; Blood Coagulation Disorders, Inherited; Dabigatran; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Kidney; Knee; Laparoscopy; Morpholines; Neoplasms; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Pyridines; Rivaroxaban; Thiophenes; Thrombophilia; Venous Thromboembolism

Newer therapeutic options available in the prevention of postoperative thromboembolism, currently focused on fondaparinux, rivaroxaban and dabigatran warrant an overall therapeutic assessment. The constitutive comparisons with enoxaparin are based on a combined outcome measure solely driven by the incidence of "asymptomatic deep vein thrombosis". Its validity as a clinically relevant endpoint is missing if antithrombotics of different classes are compared. This is because they target different phases of thrombogenesis i. e. ahead and beyond the asymptomatic stage of thrombosis. Additional concerns refer to the dosing-regimens and their practical administration: Fondaparinux, rivaroxaban and dabigatran are dosed to achieve maximum effects very close to their limits of tolerance whereas wide dosing spectra for the low molecular weight herparin (LMWH)'s indicate the potential for dose adaptation and increase. The other disadvantage to the control-heparin originates in the timing for the 1st administration which doesn't fit in with the "just-in-time" principle. So the enoxaparin-regimen is lacking in benchmark-quality - with the consequence that the meaning of the Phase III-trials does'nt go beyond a mere technical demarcation from the marketed variant of the product as defined by the stipulations in the package insert. As to tolerance the selective anticoagulants exhibit an increased risk of major and other clinically relevant bleeding, exceeding that of enoxaparin by 30% (P<0.001). The outcome of the meta-analyses on fondaparinux, rivaroxaban and dabigatran is supported by product-specific calculations and assessments of the European Medicine Equivalence Agency (EMEA). Rivaroxaban and dabigatran show significant age-dependent renal accumulation. Because the dose-finding studies were restricted to patients over 60 year old the regimens definitely established are not applicable to younger patients. The reason for the limited therapeutic index of the selective anticoagulants originates in their monovalent activity as such not adequately matching the complexity of thrombogenesis and early thrombus extension. Their class-specific limitations are compensated through more intensive dosage-regimens which result in accentuated bleeding complications. Connotatively the hypothesis emerged that antiXa- and IIa-effects interact synergistically which translates into enhanced efficacy and tolerance. Experimental studies on hirudin with pentasaccharide and hirudin with "lo

Topics: Animals; Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation; Dabigatran; Evidence-Based Medicine; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Morpholines; Polysaccharides; Practice Guidelines as Topic; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Compared to patients without cancer, patients with cancer who receive anticoagulant treatment for venous thromboembolism are more likely to develop recurrent venous thromboembolism (VTE).. To compare the efficacy and safety of three types of parenteral anticoagulants for the initial treatment of VTE in patients with cancer.. A comprehensive search for studies of anticoagulation in cancer patients including a February 2010 electronic search of: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI Web of Science.. Randomized clinical trials (RCTs) comparing low molecular weight heparin (LMWH), unfractionated heparin (UFH), and fondaparinux in patients with cancer and objectively confirmed VTE.. Using a standardized data form, data was extracted in duplicate on methodological quality, participants, interventions, and outcomes of interest that included mortality, recurrent VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia.. Of 3986 identified citations, 16 RCTs were eligible: 13 compared LMWH to UFH, two compared fondaparinux to heparin, and one compared dalteparin to tinzaparin. Meta-analysis of 11 studies showed a statistically significant reduction in mortality at three months of follow up with LMWH compared with UFH (relative risk (RR) 0.71; 95% confidence interval (CI) 0.52 to 0.98). There was little change in the effect estimate after excluding studies of lower methodological quality (RR 0.72; 95% CI 0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH showed no statistically significant reduction in VTE recurrence (RR 0.78; 95% CI 0.29 to 2.08). The overall quality of evidence was low for LMWH versus UFH due to imprecision and likely publication bias. There were no statistically significant differences between heparin and fondaparinux for the outcomes of death (RR 1.27; 95% CI 0.88 to 1.84), recurrent VTE (RR 0.95; 95% CI 0.57 to 1.60), major bleeding (RR 0.79; 95% CI 0.39 to1.63) or minor bleeding (RR 1.50; 95% CI 0.87 to 2.59). The one study comparing dalteparin to tinzaparin did not find a statistically significant difference in mortality (RR 0.86; 95% CI 0.43 to 1.73).. LMWH is possibly superior to UFH in the initial treatment of VTE in patients with cancer. Additional trials focusing on patient important outcomes will further inform the questions addressed in this review.

Topics: Anticoagulants; Dalteparin; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Polysaccharides; Randomized Controlled Trials as Topic; Secondary Prevention; Venous Thromboembolism

Thromboembolic complications are becoming more frequent in children and the use of anticoagulation has increased considerably. The most widely used agents in children, heparin, low molecular weight heparin, and warfarin all have limitations which are exaggerated in children. This has led to the study of newer agents with improved pharmacologic properties such as bivalirudin, argatroban, and fondaparinux. Clinical trials are under way to assess several new oral anticoagulants that are in late phase studies or already licensed in adults. Based on the completed studies in children, several recommendations for the use of currently available agents (bivalirudin, argatroban, and fondaparinux) are suggested for clinical use today. Additional studies need to be conducted for the these agents, so that their use may be expanded in selected indications. New regulatory requirements are leading to a number of studies in the newer anticoagulants that are yet to be licensed in adults for treatment of venous thromboembolism. Pediatric thrombosis is entering a fruitful era of research in anticoagulation management, which is sure to lead to significant changes in how children are treated in the next 10 years.

Topics: Anticoagulants; Arginine; Fondaparinux; Heparin, Low-Molecular-Weight; Hirudins; Humans; Infant; Infant, Newborn; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Venous Thromboembolism; Warfarin

Anticoagulant prophylaxis for preventing venous thrombembolism (VTE) is a worldwide established procedure in hip (HR) and knee replacement (KR) surgery, as well as in the treatment of femoral neck fractures (FNF). Different guidelines are available in the literature, with quite different recommendations. None of them is a multidisciplinary effort as the one presented. The Italian Society for Studies on Hemostasis and Thrombosis, the Italian Society of Orthopedics and Traumatology, the association of Orthopedic Traumatology of Italian Hospitals, together with the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care have set down easy and quick suggestions for VTE prophylaxis in HR and KR surgery as well as in FNF treatment. This inter-society consensus statement aims at simplifying the grading system reported in the literature, and thus at improving its proper application. Special focus is given to fragile patients, those with high bleeding risk, and on those receiving chronic antiplatelet and vitamin K antagonists treatment. A special chapter is dedicated to regional anesthesia and VTE prophylaxis.

Topics: Anesthesia; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Consensus; Femoral Neck Fractures; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Orthopedic Procedures; Patient Safety; Polysaccharides; Postoperative Complications; Postoperative Hemorrhage; Risk; Stockings, Compression; Thrombosis; Venous Thromboembolism; Vitamin K

Dabigatran is an oral direct thrombin inhibitor with a rapid onset. Patients on dabigatran do not require coagulation monitoring. Recent prospective randomized trials have shown the efficacy of dabigatran for the prevention of venous thromboembolism after knee or hip arthroplasty and for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Because dabigatran is cleared principally by the kidneys, dosage adjustments are required in the setting of renal dysfunction. There currently is no reversal agent for dabigatran although hemodialysis can facilitate its rapid removal in life-threatening circumstances. The management of severe bleeding associated with dabigatran also may include the administration of a procoagulant, such as recombinant activated factor VII. Based on recent guidelines, regional anesthesia should be used cautiously in patients taking this novel oral thrombin inhibitor.

Topics: Anesthesia, Conduction; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Chemistry, Pharmaceutical; Dabigatran; Fondaparinux; Heart Valve Prosthesis Implantation; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Randomized Controlled Trials as Topic; Thrombin; Venous Thromboembolism; Vitamin K

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

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

As an alternative to the inconvenient and labor intensive traditional anticoagulants, Factor Xa inhibitors may offer new options for the prevention and treatment of acute coronary syndromes (ACS) and venous thromboembolism (VTE). Fondaparinux, an indirect FXa inhibitor, has equivalent efficacy but decreased bleeding risk. It has been recommended by the American College of Cardiology (ACC)/American Heart Association (AHA) as the preferred anticoagulant in ACS patients with higher bleeding risk managed with a noninvasive strategy. Based on the composite results of several clinical trials, fondaparinux is also recommended for VTE prevention in the setting of major orthopedic surgery. Rivaroxaban, a direct FXa inhibitor, appears to have at least equal efficacy and safety to established anticoagulants in the prevention of VTE. With advantages such as oral administration and a wide therapeutic window, it may provide a useful alternative to current anticoagulants. Ongoing studies are exploring its use in treatment of VTE and ACS, as well as prevention of stroke among patients with atrial fibrillation. In this review, we examine the key recent studies on efficacy and safety of FXa inhibitors in ACS and VTE management.

Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Fondaparinux; Humans; Morpholines; Polysaccharides; Rivaroxaban; Thiophenes; Venous Thromboembolism

Venous thromboembolism (VTE) is a serious and potentially fatal disorder, which is often associated with a significant impact on the quality of life and on the clinical outcome of cancer patients. The pathophysiology of the association between thrombosis and cancer is complex: malignancy is associated with a baseline hypercoagulable state due to many factors including release of inflammatory cytokines, activation of the clotting system, expression of hemostatic proteins on tumor cells, inhibition of natural anticoagulants, and impaired fibrinolysis. Several risk factors, related to the patient, the disease, and the therapeutic interventions, have been identified as contributing to the occurrence of VTE. There is convincing evidence to recommend the use of heparins or fondaparinux for prevention of VTE in selected cancer patients, and, especially in some particular types of malignancies and cancer treatments. Management of VTE in patients with cancer is more challenging and bleeding complications associated with the use of anticoagulants are significantly higher in cancer patients than in those without malignancy. Important issues that need to be considered in all cases are interference with anticancer therapy, inconvenience of treatment, and impact on quality of life.

Topics: Fondaparinux; Heparin; Humans; Neoplasms; Polysaccharides; Quality of Life; Risk Factors; Venous Thromboembolism

Acutely ill medical patients are at moderate to high risk of venous thromboembolism (VTE): approximately 10-30% of general medical patients may develop deep-vein thrombosis or pulmonary embolism, and the latter is a leading contributor to deaths in hospital. Medical conditions associated with a high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, rheumatological and infectious diseases. Pre-disposing risk factors in medical patients include a history of VTE, history of malignancy, complicating infections, increasing age, thrombophilia, prolonged immobility and obesity. Hence active cancer and a history of cancer are both strongly related to VTE in medical (non-surgical) patients. Heparins, both unfractionated (UFH) and low molecular weight (LMWH) and fondaparinux have been shown to be effective agents in prevention of VTE in this setting. However, it has not yet been possible to demonstrate a significant effect on mortality rates in this population. In medical patients, unfractionated heparin has a higher rate of bleeding complications than low molecular weight heparin. Thromboprophylaxis has been shown to be effective in medical patients with cancer and may have an effect on cancer outcomes. Thromboprophylaxis in patients receiving chemotherapy remains controversial and requires further investigation. There is no evidence for the use of aspirin, warfarin or mechanical methods. We recommend either low molecular weight heparin or fondaparinux as safe and effective agents in the thromboprophylaxis of medical patients.

Topics: Anticoagulants; Aspirin; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Morpholines; Neoplasms; Polysaccharides; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism; Warfarin

To describe issues and challenges associated with venous thromboembolism (VTE) risk assessment and the use of drug therapies for VTE prophylaxis.. Patients at risk for VTE are a heterogeneous group. Systems for scoring VTE risk have been developed to identify patients who warrant prophylaxis, but most risk-scoring systems are complex and have not been validated. The optimal drug therapies and dosing strategies for reducing VTE risk are not well defined for many clinical situations, despite the availability of evidence-based guidelines from authoritative sources. Patient characteristics can influence the agent selected, dosing, timing of initiation, and duration of drug therapy. Individualized approaches to prophylaxis in patients undergoing major orthopedic surgery should take into account the presence of severe renal impairment, critical illness, morbid obesity, epidural catheters, and history of heparin-induced thrombocytopenia. To provide safe, effective VTE prophylaxis, clinicians, including health-system pharmacists, should collaborate in developing management plans tailored to patients' needs.. Preventing VTE is a challenge that can be addressed by gaining an understanding of the issues involved in patient assessment and prophylactic drug therapy and using a team approach to optimize patient outcomes.

Topics: Anticoagulants; Aspirin; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Risk Assessment; Risk Factors; Risk Reduction Behavior; Thrombocytopenia; Ultrasonography; United States; Venous Thromboembolism; Warfarin

Several randomized controlled trials have shown that pharmacological thromboprophylaxis with low-dose unfractionated heparin (UFH), low molecular weight heparin (LMWH) or fondaparinux reduces venous thromboembolism (VTE) after general surgery. No high-quality evidence supports the use of pharmacological thromboprohylaxis with traditional antithrombotic drugs in patients undergoing ambulatory surgery without additional VTE risk factors, stratified at low risk of VTE by the American College of Chest Physicians guidelines. Two new drug classes, the direct thrombin and factor Xa (FXa) inhibitors, have been developed with a potentially better risk-benefit profile.. Oral administration, predictable anticoagulant responses, low potential for drug-drug interactions render direct thrombin and factor Xa inhibitors good candidates to replace UFH, LMWH and fondaparinux for VTE prophylaxis. Most of all, the positive results of the first published clinical trials in orthopedic thromboprophylaxis allowed dabigatran etexilate and rivaroxaban to be licensed in Canada and in European Union for the prevention of VTE in patients undergoing hip-replacement and knee-replacement surgery.. No randomized trials with the new anticoagulants are ongoing in ambulatory surgery. However, currently available drugs--that is UFH, LMWH or fondaparinux--are administered subcutaneously and the new anticoagulants would offer the clear advantage of an oral administration, without request for blood testing to monitor potential adverse effects such as heparin-induced thrombocytopenia, thus potentially simplifying the treatment out of the hospital.

Topics: Administration, Oral; Ambulatory Surgical Procedures; Anticoagulants; Factor Xa Inhibitors; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Premedication; Randomized Controlled Trials as Topic; Risk Assessment; Thrombin; Venous Thromboembolism

Venous thromboembolism (VTE) is a frequent complication in cancer patients, and represents an important cause of morbidity and mortality. Especially in those patients who have a poor life expectancy, preventing death from pulmonary embolism is the mainstay of treatment. Critically ill patients should promptly be administered thrombolytic drugs. Except for selected patients requiring aggressive therapy, the initial VTE treatment should be conducted with adjusted-dose unfractionated heparin, fixed-dose low-molecular-weight heparin (LMWH) or fondaparinux. LMWHs and fondaparinux have the potential to greatly simplify the initial treatment of VTE, making the treatment of suitable patients feasible in an outpatient setting. During anticoagulant therapy, cancer patients have a twofold to fourfold higher risk of recurrent VTE and major bleeding complications when compared to non-cancer patients. The long-term administration of LMWH should be considered as an alternative to anti-vitamin K drugs in patients with advanced disease and in those with conditions limiting the use of oral anticoagulants. Prolongation of anticoagulation should be considered for as long as the malignant disorder is active.

Topics: Anticoagulants; Critical Illness; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Polysaccharides; Risk Assessment; Secondary Prevention; Venous Thromboembolism

Heparin and low molecular weight heparins have limitations in their efficacy and safety for the prevention and treatment of venous thromboembolism (VTE). New synthetic antithrombotic drugs, designed with the intention of improving the therapeutic window for prophylaxis and treatment, are in various stages of development. Synthetic pentasaccharides include fondaparinux and its long-acting analogue idraparinux. Dabigatran is a direct thrombin inhibitor that has undergone clinical trials for VTE prophylaxis and treatment. Direct factor Xa inhibitors include rivaroxiban, which has shown promising results for VTE prophylaxis and is being studied for VTE treatment, as well as apixaban and betrixaban, which are at earlier stages of clinical validation. These newer agents may represent viable options for prophylaxis and therapy as further clinical studies are performed.

Topics: Anticoagulants; Benzamides; Benzimidazoles; beta-Alanine; Dabigatran; Fondaparinux; Humans; Morpholines; Oligosaccharides; Polysaccharides; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Drug Therapy, Combination; Evidence-Based Medicine; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Injections, Intravenous; Injections, Subcutaneous; Polysaccharides; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Venous Thromboembolism; Vitamin K

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

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

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of dabigatran etexilate (DBG) for the prevention of venous thromboembolism (VTE) in patients undergoing elective hip and knee surgery based upon a review of the manufacturer's submission to the NICE as part of the single technology appraisal (STA) process. The submission's evidence came from three reasonable-quality trials comparing DBG with enoxaparin, and a comparison of DBG with fondaparinux based on the relative efficacy and safety as derived from a mixed treatment comparison (MTC) meta-analysis. DBG (220 mg and 150 mg once daily) is not inferior to enoxaparin (40 mg once daily and 30 mg twice daily) in terms of major VTE or VTE-related events (secondary outcome). Meta-analysis shows that 220 mg DBG is not inferior to enoxaparin (40 mg once daily or 30 mg twice daily) in reducing total VTE and all-cause mortality (primary outcome) in total hip or knee replacement, whereas there is uncertainty around the clinical effectiveness of 150 mg DBG for this outcome. In the MTC analysis DBG compared favourably with the other interventions, with the exception of extended enoxaparin and fondaparinux. The adverse event profile was not significantly different in those receiving DBG and those receiving enoxaparin. The submitted two-phase economic model compares DBG with enoxaparin and fondaparinux in total hip and knee replacement. The model structure is appropriate and the model assumptions are reasonable. The health states, costs, utilities and recurrence rates used are considered to be appropriate for the required analysis. The model estimated that at the licensed dose of 220 mg once daily DBG dominates enoxaparin in both total hip replacement and total knee replacement and that at the lower dose of 150 mg once daily DBG dominates enoxaparin in total hip replacement and enoxaparin dominates DBG in total knee replacement. DBG is less cost-effective than fondaparinux in total hip replacement at both doses; the cost per quality-adjusted life-year of fondaparinux versus DBG is 11,111 pounds and 6857 pounds for the higher and lower doses of DBG respectively. In total knee replacement, both DBG doses are dominated by fondaparinux. For DBG versus all comparators in all cases the cost-effectiveness results are based on small incremental cost and health benefits. Weaknesses of the submitted evidence include that methods used for screening studies,

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Clinical Trials as Topic; Comparative Effectiveness Research; Cost-Benefit Analysis; Dabigatran; Elective Surgical Procedures; Enoxaparin; Fondaparinux; Humans; Polysaccharides; Pyridines; Quality-Adjusted Life Years; Venous Thromboembolism

Bleeding is a strong predictor of death in patients hospitalized for arterial thrombosis who are treated with antithrombotic therapy, but the prognostic importance of bleeding in patients receiving antithrombotic prophylaxis for venous thromboembolism is uncertain.. Using Cox proportional hazards modeling, we examined the association between major bleeding and death at 30 days using pooled individual patient data from 8 large randomized controlled trials (n=13 085) comparing fondaparinux with control (low-molecular-weight heparin or placebo) for the prophylaxis of venous thromboembolism in hospitalized surgical or medical patients. Patients who developed major bleeding were older, were more likely to be male, had a lower body weight and lower creatinine clearance, and were more likely to be receiving fondaparinux. At 30 days, the risk of death was 7-fold higher among patients with a major bleeding event (8.6% versus 1.7%; adjusted hazard ratio, 6.96; 95% confidence interval, 4.60 to 10.51). There was a consistent pattern of reduced mortality in patients treated with fondaparinux irrespective of whether patients experienced major bleeding (6.8% versus 11.4%; hazard ratio, 0.58; 95% confidence interval, 0.27 to 1.23) or no major bleeding (1.5% versus 1.9%; hazard ratio, 0.77; 95% confidence interval, 0.59 to 1.02; P for heterogeneity=0.47).. Major bleeding in hospitalized surgical and medical patients participating in venous thromboembolism prevention trials is a strong predictor of mortality.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Clinical Trials, Phase III as Topic; Female; Fondaparinux; Hemorrhage; Humans; Male; Middle Aged; Polysaccharides; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors; Time Factors; Venous Thromboembolism

Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of approximately 50 to 60 x 10(9) platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.

Topics: Anticoagulants; Arginine; Autoantibodies; Contraindications; Disseminated Intravascular Coagulation; Fondaparinux; Heparin; Hirudins; Humans; Pipecolic Acids; Platelet Count; Platelet Factor 4; Polysaccharides; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Thrombophilia; Time Factors; Venous Thromboembolism; Vitamin K; Warfarin

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

Compared to patients without cancer, patients with cancer receiving anticoagulant treatment for venous thromboembolism are more likely to develop recurrent venous thromboembolism (VTE).. To compare the efficacy and safety of three types of anticoagulants (i.e. low molecular weight heparin (LMWH), unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in patients with cancer.. A comprehensive search for studies of anticoagulation in cancer patients including a January 2007 electronic search of : Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI the Web of Science.. Randomized clinical trials (RCTs) comparing LMWH, UFH, and fondaparinux in patients with cancer and objectively confirmed VTE.. Using a standardized data form data was extracted in duplicate on methodological quality, participants, interventions and outcomes of interest that included all cause mortality, recurrent VTE, major bleeding, minor bleeding, thrombocytopenia and postphlebitic syndrome.. Of 3986 identified citations, 26 RCTs including cancer patients as subgroups fulfilled the inclusion criteria. Cancer subgroup data was obtained for 15 of the 26 RCTs. Thirteen studies compared a LMWH to UFH while one study compared fondaparinux to UFH and one study compared dalteparin to tinzaparin. Meta-analysis of 11 studies showed a statistically significant mortality reduction in patients treated with LMWH compared with those treated with UFH (Relative risk (RR) = 0.71; 95% confidence interval (CI) 0.52 to 0.98). There was little change in the results after excluding studies of lower methodological quality (RR = 0.72; 95% CI 0.52 to 1.00). A meta-analysis of three studies comparing LMWH with UFH in reducing recurrent VTE was inconclusive (RR = 0.78; 95% CI 0.29 to 2.08). No data was available for bleeding outcomes, thrombocytopenia or postphlebitic syndrome. Compared to UFH, fondaparinux showed a non-statistically significant benefit for the outcome of death (RR = 0.52; 95% CI 0.26 to 1.05). The one study comparing dalteparin to tinzaparin showed a non-statistically significant mortality reduction with dalteparin (RR = 0.86; 95% CI 0.43 to 1.73).. Based on the included trials, LMWH is likely to be superior to UFH in the initial treatment of VTE in patients with cancer. However, there is a need for more trials to better address this research question in cancer patients. Moreover, researchers should consider making the raw data of RCTs available for individual patient data meta-analyses.

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

Patients with lower limb and pelvic trauma, or undergoing major orthopaedic surgery represent one of the highest risk groups for the development of venous thromboembolism (VTE). A significant number of pharmacological and mechanical agents have been used for the prophylaxis and treatment of VTE. Fondaparinux is a relative new pharmacological agent that selectively binds to antithrombin, and represents a new class of synthetic selective inhibitors of activated factor X. Eleven percent of the fondaparinux-related English language literature, between 2001 and 2007, refers to orthopaedic trauma, and was the sample assessed for this critical analysis review. The clinical studies evaluating the safety, efficacy, and financial implications associated with lower limb orthopaedic trauma show that fondaparinux has comparable results with the well-established use of enoxaparin. However, the scientific community has raised several issues regarding mostly fondaparinux's safety, timing of its 1(st) dose, bleeding side effects, duration of administration and lack of a reliable reversing agent. Further trials are necessary focusing on the safety and efficacy of this drug mostly in relation to clinical relevant outcomes and to different fields of trauma surgery (pelvis, long bone fractures and polytrauma patients).

Topics: Anticoagulants; Fondaparinux; Humans; Lower Extremity; Orthopedic Procedures; Pelvis; Polysaccharides; Venous Thromboembolism

Elderly patients immobilized because of an acute medical illness or surgery have a very high risk of developing venous thromboembolism (VTE). Aggressive pharmacologic prophylaxis is necessary and should be initiated either at admission for a medical condition or shortly after surgery. Aggressive prophylaxis may result in fewer patients developing VTE in the hospital and ultimately lead to fewer patients requiring full-dose anticoagulation for VTE. Mechanical prophylaxis can be used as an adjunct to an anticoagulant-based regimen but should only be used as primary prophylaxis when there is a contraindication, such as active bleeding. It is recommended that the clinician carefully evaluate the elderly patient's creatinine clearance and weight before prescribing anticoagulants, particularly when using fixed dosing regimens.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Azetidines; Benzimidazoles; Benzylamines; Dabigatran; Elective Surgical Procedures; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Prodrugs; Pyridines; Risk Factors; Vena Cava Filters; Venous Thromboembolism

Patients undergoing major orthopedic surgery--hip or knee arthroplasty, or hip fracture repair--are in the highest risk category for venous thromboembolism (VTE) solely on the basis of the orthopedic procedure itself. Despite this, nearly half of patients undergoing these procedures do not receive appropriate prophylaxis against VTE, often due to a disproportionate fear of bleeding complications in this population. Guidelines from the American College of Chest Physicians (ACCP) provide evidence-based recommendations for many aspects of VTE risk reduction in the setting of orthopedic surgery, as detailed in this review. The ACCP recommends the use of either low-molecular-weight heparin (LMWH), fondaparinux, or adjusted-dose warfarin as preferred VTE prophylaxis in patients undergoing either hip or knee arthroplasty. Fondaparinux is the preferred recommendation for patients undergoing hip fracture repair, followed by LMWH, unfractionated heparin, and adjusted-dose warfarin as alternative options. Extended-duration prophylaxis (for 4 to 5 weeks) is now recommended for patients undergoing hip arthroplasty or hip fracture repair. Patients undergoing knee arthroscopy do not require routine pharmacologic VTE prophylaxis.

Topics: Anticoagulants; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Risk Assessment; Risk Factors; Risk Reduction Behavior; Venous Thromboembolism; Warfarin

Cancer patients, especially those undergoing surgery for cancer, are at extremely high risk for developing venous thromboembolism (VTE), even with appropriate thromboprophylaxis. Anticoagulant prophylaxis in cancer surgery patients has reduced the incidence of VTE events by approximately one-half in placebo-controlled trials, and extended prophylaxis (for up to 1 month) has also significantly reduced out-of-hospital VTE events in clinical trials in this population. Clinical trials show no difference between low-molecular-weight heparin (LMWH) and unfractionated heparin in VTE prophylaxis efficacy or bleeding risk in this population, although the incidence of heparin-induced thrombocytopenia is lower with LMWH. The risk-benefit profile of low-dose anticoagulant prophylaxis appears to be favorable even in many cancer patients undergoing neurosurgery, for whom pharmacologic VTE prophylaxis has been controversial because of bleeding risks.

Topics: Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Polysaccharides; Postoperative Complications; Risk Assessment; Risk Factors; Risk Reduction Behavior; Venous Thromboembolism; Warfarin

The methodology of thromboprophylaxis post minimally invasive esophagectomy (MIE) is unclear. Thus, we compared the efficacy and safety of fondaparinux and nadroparin on the prophylaxis of venous thromboembolism (VTE) after MIE.. We conducted a randomized, double-blind, treatment-controlled study. Consecutive patients undergoing MIE randomly received a single dose of either nadroparin 2850 AxaIU (Group H) or fondaparinux 2.5 mg (Group F) daily. We used ultrasonography to identify deep vein thrombosis (DVT) on postoperative day 7. The coagulation status was examined using thromboelastography (TEG) prior to and at 0, 24, 48, and 72 h after the operation. Bleeding events were recorded during anticoagulation therapy and analysis was performed on an intention-to-treat basis.. We randomly assigned the patients to Group H (n = 57) or Group F (n = 59). Symptomatic or asymptomatic DVT was identified in seven patients in Group H and one patient in Group F (12.28% vs. 1.69%, p = 0.031). Pulmonary embolism developed in one patient in Group H, and the VTE incidence was significantly lower in Group F than Group H (1.69% vs. 14.04%, RR: 0.121, 95% CI: 0.016-0.935, p = 0.016). TEG analysis showed a more inhibited coagulation profile of Group F compared with Group H reflected by the significantly prolonged R time at 48 h and 72 h after operation (6.8 ± 2.2 min vs. 8.4 ± 2.7 min, p = 0.005; 7.1 ± 1.6 min vs. 9.2 ± 3.7 min, p = 0.002). Bleeding events were not recorded in either group.. Fondaparinux could provide similar efficacy and safety in postoperative thromboprophylaxis following MIE compared with nadroparin.

Topics: Adolescent; Adult; Aged; Anticoagulants; Double-Blind Method; Esophagectomy; Female; Fondaparinux; Humans; Male; Middle Aged; Nadroparin; Polysaccharides; Prospective Studies; Thrombelastography; Venous Thromboembolism; Young Adult

No studies have compared treatment efficacy between subcutaneous (SC) fondaparinux and oral edoxaban, which are categorized as factor Xa inhibitors, for venous thromboembolism (VTE) in the acute phase, and only a limited number of imaging-based quantitative studies have evaluated treatment.Methods and Results:In this open-label, randomized study, 50 patients with acute non-massive pulmonary embolism (PE) and/or deep-vein thrombosis (DVT) were assigned to fondaparinux or edoxaban groups. Lower-limb venous ultrasonography (US), and chest computed tomography (CT) were compared before and 7 days after treatment. Thrombus volume in DVT was calculated using quantitative ultrasound thrombosis (QUT) score on US. For evaluation of PE thrombus volume, lung perfused blood volume (PBV) on CT was calculated. The measurements before and after treatment, respectively, were as follows: QUT score: fondaparinux, 8.1±7.3 to 4.1±4.5; edoxaban, 7.7±6.3 to 4.4±4.3, both significant decreases (P=0.001, P<0.001, respectively); lung PBV: fondaparinux, 32.0±7.8 to 32.1±8.2 HU; edoxaban, 34.2±8.6 to 38.5±11.8 HU (P=0.732, P=0.426, respectively). On subjective CT-based evaluation, all pulmonary artery-related filling defects decreased/disappeared after treatment in both groups (P=NS).. Both SC fondaparinux and oral edoxaban are effective in acute VTE. Effects on thrombus regression on imaging-based quantitative measurement did not differ between the 2 drugs.

Topics: Acute Disease; Administration, Oral; Aged; Aged, 80 and over; Cyclophosphamide; Female; Fondaparinux; Humans; Injections, Subcutaneous; Male; Middle Aged; Polysaccharides; Prospective Studies; Tomography, X-Ray Computed; Ultrasonography; Venous Thromboembolism

Fondaparinux has been shown to be as effective as low molecular weight heparin\ in orthopedic surgery, with no cases of heparin induced thrombocytopenia proven until today. The\ main goal of this prospective randomized controlled trial was to define whether thromboprophylaxis\ in patients with primary osteoarthritis of the knee undergoing total knee arthroplasty (TKA) influences\ clinical parameters in the same manner in patients receiving fondaparinux as in those receiving\ nadroparin during the first 7 postoperative days. Sixty patients with primary knee osteoarthritis underwent\ unilateral TKA performed by the same surgeon and were randomized into two groups of 30\ patients receiving either fondaparinux or nadroparin thromboprophylaxis. Patients were compared\ according to the duration of operation, perioperative blood loss, laboratory results and clinical evaluation\ of the edema during the early postoperative period. No differences were found between the\ groups in the mean duration of surgery, perioperative blood loss, and most of laboratory results. The\ level of urea was significantly lower in the nadroparin group on the first and second postoperative day.\ No cases of heparin induced thrombocytopenia, deep vein thrombosis or pulmonary embolism were\ noted during the study. Study results showed both fondaparinux and nadroparin to have the same\ influence on clinical parameters during the first 7 postoperative days in patients undergoing TKA.

Topics: Adult; Anticoagulants; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Middle Aged; Nadroparin; Osteoarthritis, Knee; Polysaccharides; Postoperative Complications; Prospective Studies; Venous Thromboembolism

Venous thromboembolism (VTE) after coronary artery bypass graft (CABG) surgery may increase the postoperative morbidity and mortality. Therefore, we examined the current postoperative need for prophylactic antithrombotic therapy after CABG surgery.. This randomized, placebo-controlled, double-blind study was designed to compare the safety and efficacy of fondaparinux versus placebo in the prevention of VTE after CABG surgery. Between March 2010 and January 2013, 78 patients free from preoperative deep vein thrombosis (DVT) were enrolled, of whom 37 were randomly assigned to placebo and 41 to treatment with fondaparinux. The primary study end point was a composite, up to day 11, of (a) cumulative incidence of all VTE events, defined as symptomatic and asymptomatic DVT, and fatal and nonfatal pulmonary embolisms (efficacy end point), and (b) cumulative incidence of major hemorrhages (safety end point).. A single asymptomatic DVT of a lower extremity was detected by duplex ultrasound at the time of discharge from the hospital in the placebo-treated group, and a single major postoperative hemorrhage occurred in the fondaparinux-treated group.. The incidence of postprocedural asymptomatic DVT in this sample of patients undergoing CABG surgery was low. The overall incidence of DVT in the control and investigational treatment groups was similar. Our results showed no benefit of prophylactic postoperative fondaparinux in this population. These findings are congruent with other published studies and provide additional support for recent recommendations not to routinely use anticoagulant prophylaxis after cardiac surgery.

Topics: Anticoagulants; Coronary Artery Bypass; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Fondaparinux; Humans; Incidence; Male; Middle Aged; Polysaccharides; Postoperative Complications; Safety; Treatment Outcome; United States; Venous Thromboembolism

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 prospectively evaluate the safety of postoperative fondaparinux in comparison with low molecular weight heparin in patients undergoing uro-oncological surgery.. The present study was a prospective, single-blind, non-inferiority randomized trial. A total of 359 patients undergoing surgery for urological malignancy were enrolled from January 2011 to December 2012. A total of 298 of these patients (fondaparinux group, 152; low molecular weight heparin group, 146) were evaluable for the intention-to-treat-analysis. Patients were randomly assigned to low-dose unfractionated heparin, 5000 units twice daily until postoperative day 1 plus either fondaparinux 2.5 mg once daily or low molecular weight heparin 2000 units twice daily until postoperative day 5. The primary end-point was postoperative bleeding as by independent review, and the study was powered to show the non-inferiority of fondaparinux versus low molecular weight heparin. The other adverse events were evaluated. D-dimer and soluble fibrin monomer complex levels were measured perioperatively.. Bleeding occurred in 21 patients (12 in the fondaparinux group and 9 in low molecular weight heparin group, respectively). No significant differences were detected in the incidence of postoperative bleeding and the other adverse events between the two groups. The D-dimer was elevated on postoperative day 1 in one patient (16.6 μg/mL). In another patient, the soluble fibrin monomer complex was elevated (109 μg/mL).. Fondaparinux is non-inferior to low molecular weight heparin with respect to risk of bleeding. The favorable safety profile of fondparinux supports its prophylactic use as an alternative to low molecular weight heparin after surgery for urological malignancy.

Topics: Anticoagulants; Fondaparinux; Heparin; Humans; Polysaccharides; Postoperative Complications; Prospective Studies; Single-Blind Method; Urologic Neoplasms; Venous Thromboembolism

Real-world evidence of the effectiveness of pharmacological thromboprophylaxis for venous thromboembolism (VTE) is limited. Our objective was to assess the effectiveness and safety of thromboprophylactic regimens in Japanese patients undergoing joint replacement in a real-world setting.. Overall, 1,294 patients (1,073 females and 221 males) who underwent total knee arthroplasty (TKA) and 868 patients (740 females and 128 males) who underwent total hip arthroplasty (THA) in 34 Japanese national hospital organization (NHO) hospitals were enrolled. The primary efficacy outcome was the incidence of deep vein thrombosis (DVT) detected by mandatory bilateral ultrasonography up to post-operative day (POD) 10 and pulmonary embolism (PE) up to POD28. The main safety outcomes were bleeding (major or minor) and death from any cause up to POD28.. Patients undergoing TKA (n = 1,294) received fondaparinux (n = 360), enoxaparin (n = 223), unfractionated heparin (n = 72), anti-platelet agents (n = 45), or no medication (n = 594). Patients undergoing THA (n = 868) received fondaparinux (n = 261), enoxaparin (n = 148), unfractionated heparin (n = 32), anti-platelet agents (n = 44), or no medication (n = 383). The incidence rates of sonographically diagnosed DVTs up to POD10 were 24.3% in patients undergoing TKA and 12.6% in patients undergoing THA, and the incidence rates of major bleeding up to POD28 were 1.2% and 2.3%, respectively. Neither fatal bleeding nor fatal pulmonary embolism occurred. Significant risk factors for postoperative VTE identified by multivariate analysis included gender (female) in both TKA and THA groups and use of a foot pump in the TKA group. Only prophylaxis with fondaparinux reduced the occurrence of VTE significantly in both groups. Propensity score matching analysis (fondaparinux versus enoxaparin) showed that the incidence of DVT was lower (relative risk 0.70, 95% confidence interval (CI) 0.58 to 0.85, P = 0.002 in TKA and relative risk 0.73, 95% CI 0.53 to 0.99, P = 0.134 in THA) but that the incidence of major bleeding was higher in the fondaparinux than in the enoxaparin group (3.4% versus 0.5%, P = 0.062 in TKA and 4.9% versus 0%, P = 0.022 in THA).. These findings indicate that prophylaxis with fondaparinux, not enoxaparin, reduces the risk of DVT but increases bleeding tendency in patients undergoing TKA and THA.. University Hospital Medical Information Network Clinical Trials Registry: UMIN000001366. Registered 11 September 2008.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement; Cohort Studies; Enoxaparin; Female; Fondaparinux; Heparin; Humans; Incidence; Japan; Male; Middle Aged; Platelet Aggregation Inhibitors; Polysaccharides; Postoperative Complications; Risk Factors; Venous Thromboembolism

In several small studies, anticoagulant therapy reduced the incidence of venous thromboembolism (VTE) in patients with isolated lower-limb injuries.. To compare the efficacy and safety of fondaparinux 2.5 mg (1.5 mg in patients with a creatinine clearance between 30 and 50 mL min(-1) ) over nadroparin 2850 anti-factor Xa IU.. In this international, multicenter, randomized, open-label study, patients with an isolated non-surgical unilateral below-knee injury having at least one additional major risk factor for VTE and requiring, in the Investigator's opinion, rigid or semi-rigid immobilization for 21-45 days with thromboprophylaxis up to complete mobilization received subcutaneously once-daily either fondaparinux or nadroparin. The primary efficacy outcome was the composite of VTE (symptomatic or ultrasonographically detected asymptomatic deep vein thrombosis of the lower limb or symptomatic pulmonary embolism) and death up to complete mobilization. The main safety outcome was major bleeding.. We randomized 1349 patients (mean age 46 years): 88.7% had a bone fracture, and 83.8% had a plaster cast fitted (mean duration of immobilization, 34 days). The primary efficacy outcome occurred in 15 of 584 patients (2.6%) in the fondaparinux group and 48 of 586 patients (8.2%) in the nadroparin group (odds ratio, 0.30; 95% confidence interval [CI], 0.15-0.54; P < 0.001). A single major bleed was experienced by fondaparinux-treated patients and none by nadroparin-treated patients. These results were maintained up to the end of follow-up.. Fondaparinux 2.5 mg day(-1) may be a valuable therapeutic option over nadroparin 2850 anti-FXa IU day(-1) for preventing VTE after below-knee injury requiring prolonged immobilization in patients with additional risk factors.

Topics: Adult; Anticoagulants; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Immobilization; Leg Injuries; Male; Polysaccharides; Venous Thromboembolism

The objective of this prospective randomized controlled trial was to assess the efficacy and safety of simultaneous application of tranexamic acid and indirect factor Xa inhibitor following total knee arthroplasty (TKA).. Seventy-two primary osteoarthritis patients undergoing unilateral TKA using fondaparinux as a basic thromboprophylaxis were randomized to receive either placebo (36 patients) or tranexamic acid (36 patients). Prophylaxis against venous thromboembolism in all patients was administered with subcutaneous doses of 2.5 mg fondaparinux for 5 days post-operatively. Post-operative retransfusion volume, allogenic transfusion volumes and drain amount were recorded for each patient. Level of haemoglobin, prothrombin time, activated partial thromboplastin time and D-dimer were also assessed. Doppler ultrasonography was performed preoperatively and 7 days after surgery.. The rate of transfusion was lower in the tranexamic acid group than in the placebo group (p = 0.007). The drained blood volume during the initial 24 h and until drain removal was smaller in the tranexamic acid group than in the placebo group (p < 0.001). However, the haematologic laboratory results did not show any significant differences between the two groups. The prevalence of deep-vein thrombosis (DVT) was 4 (11.1 %) in the placebo group and 3 (8.3 %) in the tranexamic acid group (p = n.s.). There was no proximal DVT and no symptomatic pulmonary embolism in either group.. The use of tranexamic acid could reduce acute blood loss significantly without any adverse effect resulted from drug interaction with concomitant use of indirect factor Xa inhibitor following TKA. Therefore, simple combination of these drugs can be recommended to reduce post-operative blood loss as well as to reduce DVT following TKA.

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Middle Aged; Osteoarthritis, Knee; Polysaccharides; Postoperative Hemorrhage; Prospective Studies; Tranexamic Acid; Venous Thromboembolism

Standard thromboprophylaxis guidelines have not been applied universally in regions with low incidence of deep-vein thrombosis (DVT) considering risks of chemoprophylaxis and low incidence itself. We evaluated the prevalence of DVT, efficacy and safety of chemoprophylaxis, and necessity of pharmacological prevention in a low DVT incidence population.. One hundred and forty-eight patients undergoing unilateral total knee arthroplasty (TKA) were prospectively randomized to receive either a placebo or 2.5 mg of fondaparinux once daily for 5 days. Doppler ultrasonography was performed preoperatively and 7 days after surgery. The primary efficacy outcome was prevalence of DVT up to day 7. Secondary efficacy outcome was prevalence of symptomatic venous thromboembolism (VTE) up to day 90. Primary and secondary safety outcomes were incidence of major and minor bleeding, respectively.. The prevalence of total DVT was 25.7 % in placebo group and 6.8 % in fondaparinux group (p = 0.002) and the prevalence of proximal DVT was lower in both groups with no statistical difference. There was no symptomatic VTE in either group up to day 90. Although no major bleeding was developed, fondaparinux group had a significant increase of minor bleeding events (p < 0.001).. There remains low incidence of VTE following TKA in East Asians even without chemoprophylaxis. Although short-term fondaparinux protocol could reduce the incidence of overall DVT, its routine use seems debatable due to extremely rare proximal DVT and symptomatic PE and drug-related bleeding complication. However, modified and selective use of chemoprophylaxis would be considerable in high risk patients.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Double-Blind Method; Female; Fondaparinux; Humans; Male; Middle Aged; Polysaccharides; Prevalence; Prospective Studies; Ultrasonography; Venous Thromboembolism

The benefit of adding a vena cava filter to anticoagulation in treating cancer patients with venous thromboembolism remains controversial. We initiated this study as the first prospectively randomized trial to evaluate the addition of a vena cava filter placement to anticoagulation with the factor Xa inhibitor fondaparinux sodium in patients with cancer.. Sixty-four patients with deep vein thrombosis (86 %) and/or pulmonary embolism (55 %) were randomly assigned to receive anticoagulation with fondaparinux sodium with or without a vena cava filter. Endpoints included rates of complications by treatment arm, recurrent thromboembolism, complete resolution of thromboembolism, and survival rates.. No patient had a recurrent deep vein thrombosis; two (3 %) patients had new pulmonary emboli, one in each randomized cohort. Major bleeding occurred in three patients (5 %). Two patients on the vena cava filter arm (7 %) had complications from the filter. Median survivals were 493 days in the anticoagulation only arm and 266 days for anticoagulation + vena cava filter (p < 0.57). Complete resolution of venous thromboembolism occurred in 51 % of patients within 8 weeks of initiating anticoagulation.. No advantage was found for placement of a vena cava filter in addition to anticoagulation with fondaparinux sodium in terms of safety, recurrent thrombosis, recurrent pulmonary embolism, or survival in this prospective randomized trial evaluating anticoagulation plus a vena cava filter in cancer patients. Favorable complete resolution rates of thrombosis were observed on both study arms.

Topics: Aged; Aged, 80 and over; Anticoagulants; Combined Modality Therapy; Fondaparinux; Hemorrhage; Humans; Male; Middle Aged; Neoplasms; Polysaccharides; Prospective Studies; Recurrence; Survival Rate; Treatment Outcome; Vena Cava Filters; Venous Thromboembolism

Fondaparinux (FPX), a selective inhibitor of factor Xa, is widely used for the prophylaxis of venous thromboembolism (VTE) after total joint arthroplasty. However, the association between plasma FPX concentration and adverse events and the occurrence of VTE has not been clarified thus far. We aimed to prospectively evaluate these associations by measuring anti-Xa activity of FPX in patients undergoing total hip arthroplasty (THA) and investigate whether factors such as age, body weight, and renal function influence the anti-Xa levels. We enrolled 85 patients who underwent primary THA. All patients received subcutaneous FPX (2.5 mg/day for 14 days) after surgery. Anti-Xa activity was measured on postoperative days 1, 3, 7, and 14. To assess VTE, multidetector row computed tomography was performed in all patients at 1 week after surgery. The median levels of anti-Xa activity increased as follows (medians with 95 % confidence interval): 0.00 (0.00-0.01) mg/L, 0.13 (0.11-0.14) mg/L, 0.19 (0.17-0.20) mg/L, and 0.24 (0.22-0.25) mg/L on postoperative days 1, 3, 7, and 14, respectively. The plasma accumulation of FPX was more likely in patients with renal impairment than in those with normal renal function. In contrast, a poor correlation was observed between the plasma levels of anti-Xa activity and age or body weight. No differences were observed in the anti-Xa activity in patients with and without postoperative VTE or bleeding. Substantial increase in the levels of anti-Xa activity was observed, especially in patients with renal impairment, after subcutaneous administration of FPX 2.5 mg after THA.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Body Weight; Factor Xa; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Polysaccharides; Prospective Studies; Time Factors; Venous Thromboembolism

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

Prophylaxis against venous thromboembolism after elective total hip replacement is routinely recommended. Our preference has been to use mechanical prophylaxis without anticoagulant drugs. A randomised controlled trial was performed to evaluate whether the incidence of post-operative venous thromboembolism was reduced by using pharmacological anticoagulation with either fondaparinux or enoxaparin in addition to our prophylactic mechanical regimen. A total of 255 Japanese patients who underwent primary unilateral cementless total hip replacement were randomly assigned to one of three postoperative regimens, namely injection of placebo (saline), fondaparinux or enoxaparin. There were 85 patients in each group. All also received the same mechanical prophylaxis during and after the operation, regardless of their assigned group. The primary measurement of efficacy was the presence of a venous thromboembolic event by day 11, defined as deep-vein thrombosis detected by ultrasonography, documented symptomatic deep-vein thrombosis or documented symptomatic pulmonary embolism. The duration of follow-up was 12 weeks. The rate of venous thromboembolism was 7.2% with the placebo, 7.1% with fondaparinux and 6.0% with enoxaparin (p = 0.95 for the comparison of all three groups). Our study confirmed the effectiveness and safety of mechanical thromboprophylaxis without the use of anticoagulant drugs after total hip replacement in Japanese patients.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Combined Modality Therapy; Compression Bandages; Enoxaparin; Female; Fondaparinux; Humans; Intermittent Pneumatic Compression Devices; Male; Middle Aged; Polysaccharides; Postoperative Care; Postoperative Complications; Ultrasonography, Doppler, Duplex; Unnecessary Procedures; Venous Thromboembolism

The study aim was to determine the value of fondaparinux at the once-daily 1.5 mg dose in patients with moderate renal impairment (creatinine clearance between 20 and 50 ml/min). Pharmacokinetic simulations were performed using a population pharmacokinetic model based on data obtained in 756 patients undergoing major orthopedic surgery. The efficacy (venous thromboembolism) and safety (major bleeding) of 1.5 mg fondaparinux were determined by analyzing the available data obtained in all thromboprophylaxis trials using this dosage. The predicted steady-state exposure [area under the plasma concentration-time curve from 0 to 24 h (AUC0-24)] to fondaparinux between patients with moderate renal impairment receiving 1.5 mg and patients with normal renal function receiving 2.5 mg was similar. In four phase II trials (two trials versus placebo, one versus enoxaparin and one without comparator), 353 patients undergoing total hip or knee replacement (10.8% with moderate renal impairment) received fondaparinux 1.5 mg. The overall rate of venous thromboembolism and major bleeding was 10.4 and 0.3%. Fondaparinux 1.5 mg was significantly more effective than placebo (P < 0.01) and was as effective as, and tended to be safer (P = 0.05) than, twice-daily 30 mg enoxaparin. The effect was maintained in patients with moderate renal impairment. The once-daily administration of 1.5 mg fondaparinux in patients with moderate renal impairment resulted in a predicted exposure to the drug similar to that achieved with 2.5 mg in patients with normal renal function. This dosage regimen showed a favorable efficacy/safety clinical profile and should be appropriate in preventing venous thromboembolism in patients with moderate renal impairment.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Female; Fondaparinux; Humans; Kidney Diseases; Male; Middle Aged; Polysaccharides; Venous Thromboembolism

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

Twenty-three patients with fondaparinux prophylaxis over 75 years of age who underwent hip fracture surgery were enrolled in the study. Fondaparinux sodium (2.5 mg) was administered subcutaneously 6 h postoperatively and then every 24 h for 28 days. Coagulation and inflammatory parameters were measured preoperatively, then 10 h, 2, 7, and 28 days postoperatively. Increased D-dimers, positive acute phase proteins, and IL-6, and decreased negative acute phase proteins were observed preoperatively (P < 0.05). Maximum values were reached 10 h postoperatively for IL-6 and D-dimer, and on postoperative days 2 and 7 for positive acute phase proteins (P < 0.05). Transferrin, prealbumin and antithrombin levels were lowest 10 h postoperatively and on postoperative day 2 (P < 0.05). Increased D-dimers, IL-6, and positive acute phase proteins, and decreased negative acute phase proteins persisted until postoperative day 28 (P < 0.05). Prothrombin fragments (F1 + 2) reached peak levels preoperatively and decreased gradually until postoperative day 28. Fondaparinux promoted the inhibition of thrombin generation, as documented by negative correlation between F1 + 2 and FXa inhibition (r = -0.46; P < 0.001). Fondaparinux-induced FXa inhibition increased gradually until postoperative day 28. This increase correlated positively with antithrombin activity (r = 0.4; P < 0.05). Fondaparinux prophylaxis counteracted pro-thrombogenic effect associated with hip fracture and subsequent surgery without severe bleeding complications.

Topics: Acute-Phase Proteins; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Blood Coagulation Tests; Factor Xa Inhibitors; Female; Fondaparinux; Hip Fractures; Humans; Inflammation Mediators; Injections, Subcutaneous; Male; Polysaccharides; Postoperative Complications; Time Factors; Venous Thromboembolism

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

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

Venous thromboembolism (VTE) is an important complication of major orthopaedic surgery of the lower limbs. Fondaparinux, a synthetic pentasaccharide and highly selective inhibitor of activated Factor Xa, is the first in a new class of antithrombotic agents. To determine the optimal dose in Japanese patients, double-blind, placebo-controlled, dose-ranging studies of fondaparinux were conducted in patients undergoing total knee replacement (TKR) or total hip replacement (THR) surgery. Patients were randomly assigned to receive a once-daily subcutaneous injection of fondaparinux (0.75, 1.5, 2.5, or 3.0 mg) or placebo in Study 1 (TKR) and Study 2 (THR). In Study 1, the incidence of VTE was 65.3% in the placebo group and was 34.2%, 21.3%, 16.2%, and 9.5% in the groups receiving 0.75, 1.5, 2.5, and 3.0 mg fondaparinux respectively. In Study 2, the incidence of VTE was 33.8% in the placebo group and was 24.2%, 4.6%, 7.4%, and 14.4% in the 0.75, 1.5, 2.5, and 3.0 mg fondaparinux groups respectively. Dose-response effects were observed in both studies; however, no statistically significant differences in major bleeding events were found among any groups. Fondaparinux proved to be a potent anticoagulant with a favourable benefit-to-risk ratio in the prevention of VTE in these study patients.

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fondaparinux; Humans; Japan; Male; Placebos; Polysaccharides; Treatment Outcome; Venous Thromboembolism

Topics: Adult; Anticoagulants; Drug Administration Schedule; Feasibility Studies; Female; Fondaparinux; Hemorrhage; Humans; Injections, Subcutaneous; Male; Middle Aged; Pilot Projects; Polysaccharides; Prospective Studies; Secondary Prevention; Treatment Outcome; Venous Thromboembolism

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

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

Low-dose parenteral anticoagulation has demonstrated its efficacy for venous thromboembolism prophylaxis in randomized trials. However, current practice is not widely documented. In ambulatory settings, we aimed to provide an overview of the clinical use of low-dose parenteral anticoagulation in France and to assess the incidence of major bleeding and death rates.. A population-based prospective cohort study using the French national health data system (SNIIRAM) identified 142,815 adults living in five well-defined geographical areas who had a course of low-dose parenteral anticoagulants (a total of 150,389 courses) in the period 2013-2015. The main outcome measures were the types of low-dose parenteral anticoagulant, the duration and the clinical context. Adjusted incidence rate ratios (IRR) were derived from Poisson models.. Enoxaparin was the most frequently prescribed anticoagulant (58.9%) followed by tinzaparin (27.3%) and fondaparinux (10.9%). Patients receiving unfractionated heparin (N = 766, 0.53%) were older, more frequently had renal disease (48.75%) and had a higher modified HAS-B(L)ED score (≥ 3 in 61.6%) than patients receiving low-molecular weight heparin (LMWH). Surgical thrombo-prophylaxis was the most frequent indication (47.6%), followed by medical prophylaxis (29.9%). Course durations were in line with regulatory agency specifications. Only 43 (0.028%) major bleeding events and 478 (0.32%) deaths were observed. Adjusted IRRs for major bleeding or death were not significantly different for dalteparin/nadroparin, tinzaparin or fondaparinux compared to enoxaparin.. Very low incidence rates of major bleeding and all-cause mortality were observed. Our study confirms the safety of LMWHs and fondaparinux in thrombo-prophylaxis in ambulatory settings.. ClinicalTrials.gov identifier: NCT02886533.

Topics: Adult; Anticoagulants; Cohort Studies; Enoxaparin; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Incidence; Polysaccharides; Prospective Studies; Tinzaparin; Venous Thromboembolism

The present real-world study aimed to compare the efficacy and safety between fondaparinux sodium (FPX) and low molecular weight heparin (LMWH) for venous thromboembolism (VTE) prophylaxis in Chinese patients with major orthopedic surgery or trauma.. A total of 2429 patients, with major orthopedic surgery or trauma, underwent FPX (n = 1177) or LMWH (n = 1252) for VTE prophylaxis and were retrospectively reviewed. Primary outcomes, including in-hospital VTE and in-hospital major bleeding incidences, as well as the secondary outcomes, including in-hospital minor bleeding, in-hospital death, and VTE/bleeding/death within 2 months after discharge, were analyzed. Inverse probability of treatment weighting (IPTW) was conducted.. FPX group exhibited lower in-hospital VTE (0.1% vs. 0.8%; P = 0.032, crude OR = 0.11 before IPTW; P = 0.046, weighted OR = 0.12 after IPTW) and in-hospital minor bleeding (17.8% vs. 26.8%; P < 0.001, crude OR = 0.59 before IPTW; P < 0.001, weighted OR = 0.67 after IPTW) compared to LMWH group. Furthermore, no difference of in-hospital major bleeding, in-hospital death, and VTE/bleeding/death within 2 months after discharge was observed between FPX group and LMWH group (all P > 0.05). Further subgroup analyses identified, in specific cluster of patients such as older age, renal function impairment, hypertension and so on, in-hospital VTE was declined in FPX group compared to LMWH group (all P < 0.001).. FPX is probable to exhibit a superior thromboprophylaxis efficacy compared with LMWH in in-hospital patients with major orthopedic surgery or trauma, especially in some special patients such as older age, renal function impairment, hypertension, etc.

Topics: Anticoagulants; China; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Hospital Mortality; Humans; Hypertension; Orthopedic Procedures; Retrospective Studies; Venous Thromboembolism

Hospital-associated venous thromboembolism (HA-VTE) is a major cause of morbidity and mortality and is internationally recognized as a significant patient safety issue. While cirrhosis was traditionally considered to predispose to bleeding, these patients are also at an increased risk of VTE, with an associated increase in mortality. Hospitalization rates of patients with cirrhosis are increasing, and decisions regarding thromboprophylaxis are complex due to the uncertain balance between thrombosis and bleeding risk. This is further accentuated by derangements of hemostasis in patients with cirrhosis that are often considered contraindications to pharmacological thromboprophylaxis. Due to the strict inclusion and exclusion criteria of seminal studies of VTE risk assessment and thromboprophylaxis, there is limited data to guide decision making in this patient group. This guidance document reviews the incidence and risk factors for HA-VTE in patients with cirrhosis, outlines evidence to inform the use of thromboprophylaxis, and provides pragmatic recommendations on VTE prevention for hospitalized patients with cirrhosis. In brief, in hospitalized patients with cirrhosis: We suggest inclusion of portal vein thrombosis as a distinct clinically important endpoint for future studies. We recommend against the use of thrombocytopenia and/or prolongation of prothrombin time/international normalized ratio as absolute contraindications to anticoagulant thromboprophylaxis. We suggest anticoagulant thromboprophylaxis in line with local protocols and suggest low molecular weight heparin (LMWH) or fondaparinux over unfractionated heparin (UFH). In renal impairment, we suggest LMWH over UFH. For critically ill patients, we suggest case-by-case consideration of thromboprophylaxis. We recommend research to refine VTE risk stratification, and to establish the optimal dosing and duration of thromboprophylaxis.

Topics: Anticoagulants; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Liver Cirrhosis; Thrombosis; Venous Thromboembolism

Venous thromboembolism (VTE) is a common complication in patients hospitalized for acute medical illnesses. Therefore, medical inpatients require a careful VTE and bleeding risk assessment to drive optimal strategies for VTE prevention. Low molecular weight heparin and fondaparinux have long been used for inhospital prophylaxis for patients at increased risk of VTE. The selection of patients who require post-discharge prophylaxis, and the role of direct oral anticoagulants remain debated. New molecules currently under development may contribute to improve the risk benefit of VTE prevention in this setting.. This text summarizes the evidence on approved treatments and on other drugs for the prevention of VTE in acutely ill medical patients. The main focus is on their pharmacological properties, clinical efficacy and safety, and the current license approved by the FDA (Food and Drug Administration) and EMA (European Medicines Agency). The trials presented consider both inhospital and extended prophylaxis.. Thanks to the potentially favorable safety profile, factor XI inhibitors may play a role in the prevention of VTE in this setting. The expert opinion section discusses pharmacological properties, prophylaxis trials, and potential clinical applications of this novel class of drugs.

Topics: Aftercare; Anticoagulants; Benzamides; Factor XI; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Inpatients; Pyridines; Venous Thromboembolism

Topics: Animals; Anticoagulants; Enoxaparin; Factor X; Female; Fondaparinux; Nadroparin; Osseointegration; Rats; Titanium; Venous Thromboembolism

Regional citrate anticoagulation (RCA) is the recommended standard for continuous renal replacement therapy (CRRT). This study assesses its efficacy in patients admitted to critical care following cardiovascular surgery and the influence of standard antithrombotic agents routinely used in this specific group.. Consecutive cardiovascular surgery patients treated with postdilution hemofiltration with RCA were included in this prospective observational study. The primary outcome of the study was CRRT circuit life-span adjusted for reasons other than clotting. The secondary outcome evaluated the influence of standard antithrombotic agents (acetylsalicylic acid [ASA], low molecular weight heparin [LMWH] or fondaparinux as thromboprophylaxis or treatment dose with or without ASA) on filter life.. Fifty-two patients underwent 193 sessions of continous veno-venous hemofiltration, after exclusion of 15 sessions where unfractionated heparin was administered. The median filter life span was 58 hours. Filter life span was significantly longer in patients receiving therapeutic dose of LMWH or fondaparinux (79 h [2-110]), in comparison to patients treated with prophylactic dose of LMWH or fondaparinux (51 h [7-117], p < 0.001), and patients without antithrombotic prophylaxis (42 h [2-91], p < 0.0001). 12 bleeding episodes were observed; 8 occurred in patients receiving treatment dose anticoagulation, 3 in patients receiving prophylactic dose anticoagulation and 1 in a patient with no antithrombotic prophylaxis.. A postdilution hemofiltration with RCA provides prolonged filter life span when adjusted for reasons other than clotting. Patients receiving treatment dose anticoagulation had a significantly longer filter life span than those who were on prophylactic doses or ASA alone.

Topics: Anticoagulants; Citric Acid; Continuous Renal Replacement Therapy; Fibrinolytic Agents; Fondaparinux; Hemofiltration; Heparin; Heparin, Low-Molecular-Weight; Humans; Longevity; Venous Thromboembolism

Topics: Aged; Autoantibodies; Cross Reactions; Female; Fondaparinux; Heparin; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Rivaroxaban; Thrombocytopenia; Treatment Outcome; Venous Thromboembolism

Bleeding is a life-threating side effect of thromboprophylaxis with fondaparinux sodium (FPX) injection. The purpose of this retrospective study was to assess the risk factor for bleeding-related event following thromboprophylaxis with FPX after total knee arthroplasty (TKA) or total hip arthroplasty (THA). Adult patients undergoing TKA or THA at a single university hospital were administered FPX for thromboprophylaxis by subcutaneous injection of 1.5 or 2.5 mg per day. The risk factor for bleeding-related event was identified by propensity score-adjusted multivariate logistic analysis, and survival analysis was performed retrospectively in consideration of the identified risk factors. Two hundred and twenty-six patients who underwent TKA (n = 62) or THA (n = 164) were enrolled. Anaemia on postoperative day (POD) 1 was identified as a risk factor for bleeding-related event (odds ratio: 3.75, 95% confidence interval: 1.02-24.5, p = 0.04). Eighty of 226 patients were selected using a propensity score matching and patients with anaemia on POD1 in this population had a significantly higher incidence of bleeding-related event than those without anaemia (p = 0.0016, Ghen-Breslow-Wilcoxon test; p = 0.0015, log-rank test). These results suggest that anaemia on POD1 is an independent risk factor for bleeding-related event following thromboprophylaxis with FPX after TKA or THA.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Fondaparinux; Humans; Male; Middle Aged; Postoperative Hemorrhage; Venous Thromboembolism

The incidence of venous thromboembolism (VTE) and use of anticoagulation are rising in children, but treatment options remain limited. As a newer anticoagulant, fondaparinux may be a safe and effective alternative with the benefit of once-daily dosing, but there is relatively little data supporting its use.. This retrospective cohort study describes the long-term dosing, efficacy, and safety of fondaparinux for treatment of VTE in children at a single institution. The study included children <18 years old treated with fondaparinux for VTE between 2008 and 2018. Descriptive statistics were used to present the findings.. A total of 277 patients were identified and analyzed in this study. Seventy-six percent of patients reached therapeutic levels with 0 or 1 dose adjustments over a median treatment duration of 93 days. Of the patients included in the efficacy analysis, 91% of patients had improvement in their clot status, including 69% (160/233) with complete resolution and 22% (53/233) with partial resolution. Twenty-six patients (11%) had VTE recurrence, but only seven (3%) of the new thrombi developed while on fondaparinux. Major bleeding occurred in seven patients (2.5%), primarily in patients with underlying medical conditions with increased bleeding risk. Minor bleeding occurred in 53 patients (19%).. This study demonstrates the stable long-term pediatric dosing of fondaparinux with similar efficacy and safety when compared to other anticoagulants. Given its advantages, fondaparinux can be considered a reasonable alternative for treatment of VTE in children.

Topics: Adolescent; Blood Coagulation; Child; Child, Preschool; Female; Follow-Up Studies; Fondaparinux; Humans; Infant; Male; Recurrence; Retrospective Studies; Venous Thromboembolism

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

Topics: Anticoagulants; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Administration Schedule; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Pandemics; Patient Discharge; Pneumonia, Viral; Risk Factors; SARS-CoV-2; Venous Thromboembolism

Topics: Child; Enoxaparin; Fondaparinux; Humans; Retrospective Studies; Venous Thromboembolism

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

Topics: Aged; Anticoagulants; Betacoronavirus; Coronavirus Infections; COVID-19; Enoxaparin; Female; Fondaparinux; Heparin; Humans; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Treatment Outcome; Venous Thromboembolism

Topics: Aged; Aged, 80 and over; Anticoagulants; COVID-19; COVID-19 Drug Treatment; Enoxaparin; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Humans; Italy; Male; Middle Aged; Retrospective Studies; Risk Assessment; Risk Factors; Thrombosis; Treatment Outcome; Venous Thromboembolism

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

The objective of this study was to identify the optimal duration of pharmacological thromboprophylaxis after outpatient endovenous laser ablation (EVLA).. In this multicentre retrospective study in a university hospital, regional hospital and private practices, we collected the demographic, procedural and outcome data of all consecutive patients with varicose veins class C2 to C6 undergoing outpatient EVLA of truncal and accessory veins between February 2009 and December 2015. The cumulative primary efficacy endpoint consisted of endovenous heat-induced thrombosis (EHIT) class 2–4, deep vein thrombosis (DVT) and pulmonary embolism (PE) diagnosed with duplex ultrasound or computed tomography angiography after 1 and 4 weeks of follow-up. Cumulative secondary endpoints were complete ablation of the treated veins and major bleeding, skin burns and infection.. A total of 864 patients were treated with EVLA as an outpatient procedure. Of those, 35 patients were omitted because of therapeutic anticoagulation or dual antiplatelet therapy. Another 36 cases were excluded as the patients received pharmacological thromboprophylaxis for 5 days. A total of 793 were included in the final analysis. Of those, 225 patients (28.4%) received fondaparinux 2.5 mg s.c. for 3 days, 166 patients (20.9%) received rivaroxaban 10 mg p.o. for 3 days and 402 patients (50.7%) received rivaroxaban 10 mg for 10 days. The incidence of EHIT class 2–4 was 0.8% (n = 6) in total, 1.3% (n = 6) in group 1 (treated for 3 days) and 0.3% (n = 1) in group 2 (treated for 10 days) (odds ratio [OR] 0.19, confidence interval [CI] 0.02–1.66, p = 0.133). The cumulative primary composite endpoint at 4-week follow-up was 1.1% (n = 9) and was 2.1% (n = 8) in group 1 and 0.3% (n = 1) in group 2 (OR 0.0.12, CI 0.01–0.96, p = 0.046). Propensity score-matched analysis revealed no significant difference in the composite primary endpoint (CI −0.074 to 0.26). Complete occlusion rate was 99.2% in group 1 and 98.8% in group 2 (OR 0.61, CI 0.15–2.59, p = 0.506). No PE or major bleeding events occurred in either group. Propensity score-matched analysis showed no significant difference in the secondary endpoints.. Using propensity score-matched analysis we showed that pharmacological thromboprophylaxis after EVLA seems to be equally effective with 3 days or 10 days of treatment with a similar success rate and safety profile. Undoubtedly, a large randomised control trial, ideally including a group without pharmacological thromboprophylaxis, is needed to draw more definitive conclusions on the optimal duration of pharmacological post-EVLA thromboprophylaxis.

Topics: Ambulatory Surgical Procedures; Dose-Response Relationship, Drug; Drug Administration Schedule; Endovascular Procedures; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Laser Therapy; Male; Middle Aged; Propensity Score; Retrospective Studies; Rivaroxaban; Saphenous Vein; Varicose Veins; Venous Thromboembolism

Clinically apparent venous thromboembolism (VTE) occurs in approximately 7% of patients with membranous nephropathy. Hypoalbuminemia at diagnosis is an independent risk factor for VTE, and risk increases significantly as albumin falls. Optimal prophylactic and treatment anticoagulation regimens in the nephrotic syndrome remain unproven but novel oral anti-coagulants have become attractive therapeutic options. We describe a patient diagnosed with anti-phospholipase A2 receptor antibody positive membranous nephropathy and recurrent VTE while on therapeutic dosing of apixaban. A direct factor Xa inhibitor, apixaban has been shown to be non-inferior to warfarin for the treatment of VTE in the general population. However, because it is highly protein-bound, apixaban may have altered pharmacokinetics and pharmacodynamics in patients with nephrotic syndrome and hypoalbuminemia. This case report highlights the need for further studies of direct oral anticoagulants to fully assess their effectiveness in this high-risk population.

Topics: Factor Xa Inhibitors; Fondaparinux; Glomerulonephritis, Membranous; Humans; Male; Middle Aged; Pyrazoles; Pyridones; Recurrence; Serum Albumin; Venous Thromboembolism

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

Anticoagulants are used following total knee arthroplasty (TKA) to prevent venous thromboembolism (VTE). These drugs reduce VTE risk but may lead to bleeding-related complications. Recently, surgeons have advocated using antiplatelet agents including aspirin (ASA). However, there is no consensus regarding which medication has the optimal risk/benefit profile. The purpose of this study was to compare rates of VTE using different anticoagulants in anticoagulation-naïve patients being discharged home after TKA.. A national private insurance database was used to identify patients undergoing unilateral TKA. Patients with a prior history of VTE were excluded. Anticoagulants included ASA, low molecular weight heparin (LMWH), warfarin, factor Xa inhibitors (XaI), and fondaparinux. Postoperative complications, including VTE, blood transfusion, myocardial infarction, and hematoma, were identified using ICD-9 diagnosis codes. Risk of each complication was compared between groups using multivariate logistic regression controlling for demographics, length of stay, and comorbidities.. Of 30,813 patients, 1.82% were diagnosed with VTE. Using ASA as a baseline, there was significantly decreased risk of VTE with LMWH (OR 0.47), XaI (OR 0.50), and fondaparinux (OR 0.32). There was significantly higher risk of transfusion with LMWH (OR 1.56) and fondaparinux (OR 1.84), but no difference in hematoma between medications.. This study shows that there is a decreased risk of VTE with LMWH, XaI, and fondaparinux compared to ASA. However, these medications also had higher rates of bleeding-associated complications. The choice of pharmacologic prophylaxis should be made based on a balance of the risk/benefit profile of each medication.. III.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Aspirin; Chemoprevention; Databases, Factual; Factor Xa Inhibitors; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Logistic Models; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Risk Assessment; Venous Thromboembolism; Warfarin

Essentials Spontaneous HIT syndrome clinically/serologically resembles HIT but without proximate heparin. Rarely, spontaneous HIT syndrome complicates total knee arthroplasty surgery. Mesenteric vein thrombosis is a rare presentation of spontaneous HIT syndrome. IVIg rapidly corrects thrombocytopenia by inhibiting heparin-independent platelet activation. SUMMARY: Spontaneous heparin-induced thrombocytopenia (HIT) syndrome is an autoimmune HIT (aHIT) disorder characterized by thrombocytopenia, thrombosis, and HIT antibodies despite no proximate heparin exposure. For unknown reasons, many cases occur after total knee arthroplasty. A 52-year-old woman presented 12 days posttotal knee replacement (aspirin thromboprophylaxis) with gastrointestinal bleeding (superior mesenteric vein thrombosis); the platelet count was 63 × 10

Topics: Anticoagulants; Arginine; Arthroplasty, Replacement, Knee; Female; Fondaparinux; Gastrointestinal Hemorrhage; Heparin; Humans; Immunoglobulins, Intravenous; Middle Aged; Pipecolic Acids; Platelet Activation; Platelet Count; Serotonin; Sulfonamides; Thrombocytopenia; Thrombosis; Venous Thromboembolism

Pharmacological thromboprophylaxis after colorectal cancer (CRC) surgery is internationally recommended for venous thromboembolism (VTE) prevention. The aim of this retrospective study was to evaluate the risk factors of postoperative bleeding after elective surgery for patients with primary CRC receiving pharmacological thromboprophylaxis of fondaparinux or enoxaparin.. We experienced consecutive 266 patients who underwent elective surgery for CRC during the study period. Finally, the medical records of 218 patients with CRC administrated fondaparinux or enoxaparin following surgery were retrospectively reviewed to evaluate symptomatic VTE until 28 days and postoperative bleeding comparing perioperative D-dimer levels.. The significant differences in TNM classification staging and type of thromboprophylaxis were observed between postoperative bleeding-negative and bleeding-positive group. There was no statistical significance among other backgrounds of patients between the two groups. One case (0.46%) of symptomatic VTE and total 11 cases (5%) of postoperative bleeding were observed. In the univariate analysis, fondaparinux thromboprophylaxis and early disease-stage CRC (stages 0 and I) were associated with risk for postoperative bleeding. Multivariate analysis revealed that fondaparinux thromboprophylaxis was identified as an independent risk factor of postoperative bleeding. Moreover, preoperative levels of D-dimer in patients with stage IV CRC were significantly higher than those with the other stages. The significant elevation in preoperative D-dimer was also observed in patients with stage II CRC compared to those with stage I CRC. Perioperative levels of D-dimer in patients with advanced disease-stage CRC (stages II, III, and IV) were significantly higher than those in patients with early disease-stage CRC.. Fondaparinux administration and early disease-stage CRC appeared to be risk factors for postoperative bleeding in patients with pharmacological thromboprophylaxis undergoing surgical treatment for CRC. Patients' hypercoagulative condition depending on disease progression of CRC might be related to the occurrence of postoperative bleeding following CRC surgery.

Topics: Aged; Anticoagulants; Colorectal Neoplasms; Disease Progression; Elective Surgical Procedures; Enoxaparin; Female; Fondaparinux; Humans; Incidence; Male; Middle Aged; Neoplasm Staging; Postoperative Hemorrhage; Prognosis; Retrospective Studies; Treatment Outcome; Venous Thromboembolism

It is well established that abdominoplasty confers a uniquely high risk of venous thromboembolism (VTE) complications. However, chemoprophylaxis is not routinely utilized due to the risk of bleeding complications. Fondaparinux, a factor Xa inhibitor FDA approved in 2001 for postoperative VTE prophylaxis, has emerged as a safe option for preventing VTE complications after high-risk surgeries.. The goal of this study was to examine the effectiveness and safety of fondaparinux for VTE chemoprophylaxis in patients undergoing abdominoplasty.. This is a single-center retrospective chart review from January 2008 to December 2014 of 492 patients who underwent abdominoplasty with or without an additional body procedure. Prior to 2011, no VTE chemoprophylaxis was utilized (n = 233). In 2011, the routine employment of postoperative chemoprophylaxis with fondaparinux was implemented (n = 259). Patient demographics and 2005 Caprini scores were evaluated. Primary outcomes included postoperative VTE and bleeding complications.. There were no statistical differences in patient demographics or median Caprini score. The treatment group demonstrated a statistically significant reduction in the rate of VTE compared with the nontreatment group (0% vs 2.1%, respectively, P = 0.02). There was no statistically significant difference in the rate of hematoma requiring reoperation between the nontreatment and treatment groups (1.7% vs 2.3%, P = 0.76) or blood loss requiring transfusion (0% vs 0.8%, P = 0.5).. Fondaparinux for VTE chemoprophylaxis after abdominoplasty is efficacious in decreasing the risk of VTE in this susceptible patient population without increasing the risk of postoperative bleeding complications.

Topics: Abdominoplasty; Adult; Aged; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Middle Aged; Postoperative Hemorrhage; Retrospective Studies; Treatment Outcome; Venous Thromboembolism; Young Adult

A 45-year-old woman who required lifelong anticoagulation for recurrent thrombosis had her therapeutic choices limited by heparin-induced thrombocytopenia and abnormal pharmacokinetics (greatly reduced absorption) resulting from short gut syndrome from extensive gut resection after mesenteric thrombosis. As an alternative to inconvenient and expensive injections of fondaparinux, personalized dosing of a direct oral anticoagulant was sought using clinical pharmacology techniques. Enteral absorption was ascertained with small test doses of apixaban, and the ability of supraconventional doses to deliver effective concentrations was verified.

Topics: Administration, Oral; Chronic Disease; Female; Fibrinolytic Agents; Follow-Up Studies; Fondaparinux; Humans; Injections, Subcutaneous; Middle Aged; Patient Safety; Polysaccharides; Precision Medicine; Pyrazoles; Pyridones; Risk Assessment; Severity of Illness Index; Short Bowel Syndrome; Treatment Outcome; Venous Thromboembolism

This article evaluates trends in venous thromboembolism (VTE) prophylaxis during delivery hospitalizations in the United States.. We utilized an administrative database to determine if women hospitalized for vaginal or cesarean delivery received pharmacologic VTE prophylaxis, mechanical VTE prophylaxis, or both from January 2011 through March 2015. Mechanical prophylaxis included sequential compression devices, graduated compression stockings, and other pneumatic devices. Pharmacologic prophylaxis included unfractionated heparin, low molecular weight heparin, or fondaparinux. Probability of use of thromboprophylaxis for individual hospitals was estimated in an adjusted model.. A total of 956,428 women who underwent cesarean and 1,914,142 women who underwent vaginal delivery were included in the analysis. Cesarean VTE prophylaxis declined between 2011 (50.3%) and 2015 (47.7%;. While many hospitals appear to be following best clinical practices, some do not provide routine cesarean VTE prophylaxis. Minimizing care quality variation may improve maternal safety.

Topics: Adolescent; Adult; Anticoagulants; Cesarean Section; Databases, Factual; Delivery, Obstetric; Female; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Intermittent Pneumatic Compression Devices; Linear Models; Postpartum Period; Pregnancy; Risk Factors; Stockings, Compression; United States; Venous Thromboembolism; Young Adult

This study was designed to clarify the factors affecting the efficacy, adverse events, and pharmacokinetics of fondaparinux in Japanese patients undergoing artificial knee replacement surgery.. Fondaparinux (1.5 mg/d) was administered subcutaneously to patients (n = 30) at 24 hours after surgery, and blood samples were taken at various time points thereafter. Venous thromboembolism (VTE), presence of bleeding, and pharmacokinetics were evaluated. Multivariate analysis and population pharmacokinetic analysis were performed to detect factors that necessitated withdrawal of fondaparinux and individual differences in its pharmacokinetics.. VTE was observed in 9 patients (3 for whom administration was continued and 6 for whom withdrawal was necessary). The maximum plasma concentration of fondaparinux was found to be a significant factor determining withdrawal of the drug. Population pharmacokinetic analysis demonstrated that individual renal function and body weight were significant factors associated with apparent clearance and volume of distribution, respectively.. A high maximum plasma concentration of fondaparinux may result in subcutaneous hemorrhage, necessitating withdrawal of fondaparinux administration. The patient's kidney function and body weight also contribute to individual differences in pharmacokinetics. We recommend considering an adjustment to the dose of fondaparinux based on body weight in patients undergoing artificial knee replacement surgery.
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Topics: Aged; Aged, 80 and over; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Middle Aged; Polysaccharides; Venous Thromboembolism

Topics: Adult; Anticoagulants; Antithrombins; Dabigatran; Drug Therapy, Combination; Factor Xa Inhibitors; Fondaparinux; Humans; Lung Neoplasms; Male; Recurrence; Thrombophilia; Thrombosis; Venous Thromboembolism

Postoperative anemia is a common complication after total hip arthroplasty (THA). However, the effect of edoxaban on postoperative anemia after THA remains unclear. Here, we retrospectively evaluated the clinical assessment of postoperative anemia and the associated changes of coagulation parameters in patients undergoing thromboprophylaxis with edoxaban compared with fondaparinux as a conventional anticoagulant thromboprophylactic agent after THA.. One hundred and forty-nine patients who underwent THA from July 2010 to June 2012 were divided into two groups, according to whether they were operated on before or after the approval of edoxaban: the fondaparinux group (Group F: 86 patients) and the edoxaban group (Group E: 63 patients). The frequency of postoperative anemia and blood coagulation values were investigated.. Postoperative anemia developed more frequently in Group E than in Group F after surgery. However, the degree of postoperative anemia showed no significant difference between the groups. Meanwhile, prothrombin time (PT), prothrombin time-international normalized ratio (PT-INR), and activated partial thromboplastin time were markedly higher in patients with edoxaban-associated postoperative anemia, which showed an increased potential to predict the occurrence of postoperative anemia. Additionally, both PT and PT-INR in Group E were also correlated with the volume of estimated blood loss.. The frequency of postoperative anemia was increased in patients treated with edoxaban, compared to fondaparinux, after THA. Edoxaban thromboprophylaxis might, therefore, require more careful monitoring to prevent postoperative anemia. Additionally, particular prolongation of PT and PT-INR induced by edoxaban treatment might predict postoperative anemia.

Topics: Aged; Aged, 80 and over; Anemia; Anticoagulants; Arthroplasty, Replacement, Hip; Blood Coagulation Tests; Chemoprevention; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Middle Aged; Predictive Value of Tests; Pyridines; Retrospective Studies; Thiazoles; Venous Thromboembolism

Increased exposure to fondaparinux, as observed in patients with renal impairment, may increase bleeding risk. This study aims to determine the time course of major bleeding after major orthopaedic surgery, identify predictors of bleeding and simulate the effect of a reduced dose of fondaparinux on bleeding for patients with moderate renal impairment (creatinine clearance = 20-50 ml min. Data including fondaparinux anti-Xa activities from two multicentre prospective cohorts were used. In the first cohort, patients (n = 957) received fondaparinux 2.5 mg once a day. In the second, patients with moderate renal impairment (n = 436) received 1.5 mg once per day. The time-to-major bleeding after the end of surgery was modelled using a parametric survival analysis in NONMEM.. The observed rate of major bleeding up to day 11 was 5.2%. The time-to-event analysis indicated that the hazard of bleeding was highest in the first days following surgery and then remained low thereafter. Independent significant predictors of an increased hazard of major bleeding were male sex, lower body weight and increased drug exposure. Simulated rates of major bleeding up to day 11 in patients with moderate renal impairment were 6.5% with fondaparinux 2.5 mg once daily and 3.8% with fondaparinux 1.5 mg once daily.. The hazard of major bleeding is highest in the first postoperative days and increases with fondaparinux exposure. To reduce the risk of bleeding in patients with moderate renal impairment, this study supports the use of a lower dose of fondaparinux 1.5 mg once daily.

Topics: Adult; Aged; Aged, 80 and over; Creatinine; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Follow-Up Studies; Fondaparinux; Glomerular Filtration Rate; Humans; Incidence; Kidney; Male; Middle Aged; Orthopedic Procedures; Postoperative Hemorrhage; Prognosis; Prospective Studies; Renal Elimination; Risk Assessment; Risk Factors; Time Factors; Venous Thromboembolism

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

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

Fondaparinux, as a factor Xa-inhibitor, is used off label to manage heparin-induced thrombocytopenia (HIT), but little experience with HIT patients has been reported in the literature. Moreover, the use of fondaparinux for full anticoagulation in critically ill patients with HIT and renal insufficiency is limited.. A trauma patient, who had received low molecular weight heparin (LMWH) and heparin to treat venous thromboembolism, developed thrombocytopenia and multiple organ dysfunction in the intensive care unit (ICU). Also, her deep venous thromboembolism (DVT) continued to progress.. The final diagnosis was HIT.. Fondaparinux was temporarily used for anticoagulation treatment of DVT for 7 days when another anticoagulant (argatroban) was unavailable. Although the patient had kidney dysfunction, a full therapeutic dose of 7.5 mg fondaparinux was administered every morning through subcutaneous injection for consecutive 7 days.. The patient's thrombocytopenia and thrombosis were successfully treated without bleeding complications during therapeutic fondaparinux administration.. This is the first case reporting the successful use of fondaparinux for full anticoagulation for DVT in a critically ill patient with HIT and renal insufficiency. Our experience suggests that fondaparinux might be an alternative for anticoagulation treatment in patients with HIT and kidney dysfunction if another anticoagulant (argatroban) is unavailable.

Topics: Aged, 80 and over; Anticoagulants; Critical Illness; Factor Xa Inhibitors; Female; Fondaparinux; Heparin; Humans; Polysaccharides; Thrombocytopenia; Venous Thromboembolism

Essentials Critically ill cancer patients require pharmacologic prophylaxis for venous thromboembolism (VTE). Patients from 566 hospitals in the United States between 2010 and 2014 were included. Low-molecular-weight heparin (LMWH) prophylaxis was not associated in a reduction of VTE rates. LMWH prophylaxis was associated with a reduction in bleeding and heparin induced thrombocytopenia. SUMMARY: Background Critically ill patients with cancer are at increased risk of venous thromboembolism (VTE) from physical and cellular factors, requiring pharmacologic prophylaxis to reduce the risk of VTE. Objectives To assess whether low-molecular-weight heparin (LMWH) prophylaxis reduces in-hospital rates of VTE or improves clinical outcomes compared with unfractionated heparin (UFH) prophylaxis in critically ill patients with cancer. Methods We used a propensity-matched comparative-effectiveness cohort from the Premier Database. Patients aged 18 years or older with a primary diagnosis of cancer, intensive care unit admission and VTE prophylaxis within 2 days of admission between 1 January 2010 and 31 December 2014 were included. Patients were divided into LMWH or UFH prophylaxis groups. Results A total of 103 798 patients were included; 75 321 (72.6%) patients received LMWH and 28 477 (27.4%) patients received UFH. Propensity analysis matched (2 : 1) 42 343 LMWH patients and 21 218 UFH patients. Overall, LMWH was not associated with a decreased incidence of VTE (5.32% vs. 5.50%). LMWH prophylaxis was associated with a reduction in pulmonary embolism (0.70% vs. 0.99%), significant bleeding (13.3% vs. 14.8%) and heparin-induced thrombocytopenia (HIT) (0.06% vs. 0.19%). In non-metastatic solid disease, LMWH was associated with decreased VTE (4.27% vs. 4.84%) and PE (0.47% vs. 0.95%). Conclusions The use of an LMWH for VTE prophylaxis was not associated with a reduction in the incidence of in-hospital VTE as compared with UFH, but was associated with significant reductions in PE, clinically important bleeding events, and incidence of HIT in critically ill patients with cancer.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Comparative Effectiveness Research; Critical Illness; Databases, Factual; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasms; Risk Factors; Thrombocytopenia; Time Factors; Treatment Outcome; United States; Venous Thromboembolism; Young Adult

Which treatments for lower extremity superficial thrombophlebitis (ST) are associated with lower rates of venous thromboembolic events (VTEs) vs placebo?. A dose of 2.5 mg of fondaparinux administered subcutaneously once daily for 45 days is associated with fewer cases of symptomatic VTE without an increase in major bleeding vs placebo. Low-molecular-weight heparin (LMWH) and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with lower rates of ST extension or recurrence vs placebo, but data regarding symptomatic VTE remain inconclusive. Oral rivaroxaban requires further evaluation.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Factor Xa Inhibitors; Female; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Lower Extremity; Male; Randomized Controlled Trials as Topic; Review Literature as Topic; Stockings, Compression; Thrombophlebitis; Venous Thromboembolism

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction mediated by platelet-activating antibodies that target complexes of platelet factor 4 and heparin. Patients are at markedly increased risk of thromboembolism.. These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about diagnosis and management of HIT.. ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.. The panel agreed on 33 recommendations. The recommendations address screening of asymptomatic patients for HIT, diagnosis and initial management of patients with suspected HIT, treatment of acute HIT, and special situations in patients with acute HIT or a history of HIT, including cardiovascular surgery, percutaneous cardiovascular intervention, renal replacement therapy, and venous thromboembolism prophylaxis.. Strong recommendations include use of the 4Ts score rather than a gestalt approach for estimating the pretest probability of HIT and avoidance of HIT laboratory testing and empiric treatment of HIT in patients with a low-probability 4Ts score. Conditional recommendations include the choice among non-heparin anticoagulants (argatroban, bivalirudin, danaparoid, fondaparinux, direct oral anticoagulants) for treatment of acute HIT.

Topics: Administration, Oral; Anticoagulants; Arginine; Cardiovascular Surgical Procedures; Chondroitin Sulfates; Dermatan Sulfate; Evidence-Based Medicine; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Platelet Count; Recombinant Proteins; Renal Replacement Therapy; Sulfonamides; Thrombocytopenia; Venous Thromboembolism

Limited data is available regarding the pharmacological prophylaxis for venous thromboembolism (VTE) in Asian patients undergoing total knee arthroplasty or total hip arthroplasty (TKA/THA).. We performed a population-based epidemiological study using the Health Insurance Review and Assessment Service database to estimate the rate of pharmacological thromboprophylaxis and its impact on VTE in Korean patients who underwent TKA/THA between 2009 and 2013.. We identified 306,912 cases (TKA, 261,260; THA, 45,652). The pharmacological thromboprophylaxis rate was 57.16% (TKA, 58.32%; THA, 50.51%), which increased from 42.81% in 2009 to 65.92% in 2013 (P = 0.0165). Both low-molecular-weight-heparin (22.42%) and rivaroxaban (22.71%) were the most common drugs for prophylaxis. The number of patients aged ≥ 60 years (87.31% vs. 81.01%, P < 0.0001), cases requiring general anesthesia (20.70% vs. 18.37%, P < 0.0001), and cases requiring long hospital stay (median, 13 days vs. 12 days, P < 0.0001) were significantly greater in the pharmacological prophylaxis group. The incidence of VTE within 3 months of surgery was 1.52% (TKA, 1.46%; THA, 1.87%). Patients with pharmacological prophylaxis had higher VTE rates (TKA, 1.69% vs. 1.14%; THA, 2.30% vs. 1.43%) than those without prophylaxis, with advanced age, use of general anesthesia, and a longer hospital stay increasing the risk of VTE. However, rivaroxaban significantly reduced the incidence of VTE following TKA (0.82% vs. 1.14%; odd ratio [OR], 0.72; 95% CI, 0.65-0.79). Moreover, ≥ 10 days of pharmacological thromboprophylaxis was significantly associated with lower incidence of VTE after TKA (1.33% vs. 1.52%; OR, 0.87; 95% CI, 0.81-0.94).. This represents the largest epidemiological study showing a gradual increase in the use of pharmacological prophylaxis in Korean patients undergoing TKA/THA. Although the incidence of VTE is still low without pharmacological prophylaxis, this study demonstrates that the incidence of VTE can be reduced further using appropriate pharmacological thromboprophylaxis strategies.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Erythrocyte Transfusion; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Polysaccharides; Postoperative Complications; Postoperative Hemorrhage; Republic of Korea; Risk Factors; Rivaroxaban; Venous Thromboembolism

Thrombotic complications are increasing at a steady and significant rate in children resulting in the more widespread use of anticoagulation in this population. Anticoagulant drugs in children can be divided into the standard agents (heparin, low molecular weight heparin, and vitamin K antagonists) and alternative agents (argatroban, bivalirudin, and fondaparinux). This review will compare and contrast the standard and alternative anticoagulants and suggest situations in which it may be appropriate to use argatroban, bivalirudin, and fondaparinux. Clearly, the standard anticoagulants all have significant shortcomings including variable pharmacokinetics, issues with therapeutic drug monitoring, frequency of administration, efficacy, and adverse effects. The alternative anticoagulants have properties which overcome these shortcomings and prospective clinical trial data are presented supporting the current and future use of these agents in place of the standard anticoagulants.

Topics: Anticoagulants; Arginine; Blood Coagulation; Child; Drug Monitoring; Fondaparinux; Heparin; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Thrombosis; Venous Thromboembolism; Warfarin

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

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

Venous thromboembolism is the most common preventable cause of hospital death. The objective of this study was to clarify risk factors for postoperative bleeding related to thromboprophylaxis after laparoscopic colorectal cancer surgery.. The study was conducted at 23 Japanese institutions and included patients with colorectal cancer who underwent laparoscopic or open surgery followed by fondaparinux treatment. We performed a retrospective analysis from a prospectively maintained database. We used multivariate analyses to evaluate clinical risk factors for prophylaxis-related bleeding events.. Different prophylactic treatments for postoperative venous thromboembolism may be necessary in laparoscopic vs open surgery for colorectal cancer.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Colorectal Neoplasms; Female; Fondaparinux; Humans; Japan; Laparoscopy; Male; Middle Aged; Polysaccharides; Postoperative Hemorrhage; Retrospective Studies; Risk Factors; Venous Thromboembolism

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 decision concerning the introduction of primary and secondary prophylaxis of venous thromboembolism (VTE) in patients with solid brain neoplasms and brain metastases is often challenging due to the concomitant increased risk of intracranial hemorrhage and to limited evidence from available literature. A standardized questionnaire composed of nine multiple-choice questions regarding primary VTE prevention in non-surgical patients during high-risk conditions and VTE secondary prevention in patients with a solid brain neoplasm or cerebral metastases was sent via electronic mail to all the members (n = 2420) of the Italian Federation of the Internal Medicine Hospital Executives' Associations (FADOI) in June 2015. Three hundred and fifty two physicians (14.5%) returned it (participants' median age 51 years; females 46.9%). The majority of respondents prescribe primary thromboprophylaxis (usually with heparin) in non-surgical patients with solid brain neoplasms and brain metastases in concomitance with high-risk conditions. Full-dose anticoagulation with either low-molecular-weight heparin or fondaparinux is the preferred option for acute VTE (69.6%), while a reduced dose is chosen by 21.0% of physicians. The presence of a highly vascular brain neoplasm histotype mandates the prescription of a reduced-dose antithrombotic regimen in a minority of respondents. Vena cava filter placement is an option for the treatment of acute VTE in more than 6% of respondents. Anticoagulants are often prescribed for both VTE primary prevention and treatment. In conclusion, physicians' managements are partially in contrast to recent guidelines, reinforcing the need for educational programs and other studies in this setting.

Topics: Adult; Anticoagulants; Brain Neoplasms; Clinical Competence; Consensus; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Italy; Male; Middle Aged; Physicians; Polysaccharides; Surveys and Questionnaires; Venous Thromboembolism

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

Fondaparinux (FPX), a synthesized factor Xa inhibitor, is one of the most popular anticoagulants for the prevention of postoperative venous thromboembolism (VTE). Although routine monitoring is not required, the bleeding adverse events cannot be neglected, and the measurement of anti-Xa activity is expected to be monitored. The primary purpose of this study is to evaluate the performances of 2 chromogenic assays for the detection of anti-Xa activity. Furthermore, the pharmacokinetics of FPX was examined using chromogenic assays. Anti-Xa activity was measured using 2 FPX-based chromogenic substrates (S2222 and STA-Liquid Anti-Xa). The reproducibility, detection limits, linearity, and correlations between the substrates were examined using normal plasma doped with low and high concentrations of FPX formulation. In addition, anti-Xa activity in 235 clinical samples from 164 cases treated was measured, and the pharmacokinetics of FPX was evaluated. Both of the tested substrates were capable of accurately measuring the anti-Xa activity of FPX, with a lower limit of 0.05 μg/mL and a coefficient of variation of less than 10%. The repeated administration of FPX induced a gradual but significant increase in the anti-Xa activity, which was negatively correlated with body weight and estimated glomerular filtration rate. No significant correlation between the anti-Xa activity and the occurrence of postoperative VTE or bleeding event was observed. Anti-Xa activity can be successfully determined using 2 chromogenic assays and automated biochemical analyzers. The clinical significance of anti-Xa activity monitoring should be examined in the future study.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Body Weight; Chromogenic Compounds; Clinical Chemistry Tests; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Fondaparinux; Glomerular Filtration Rate; Hemorrhage; Humans; Male; Middle Aged; Polysaccharides; Postoperative Complications; Venous Thromboembolism

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

We report a case of venous thromboembolism during the cisplatin-based adjuvant chemotherapy. A 49-year-old woman who was undergone left lower lobectomy for the lung cancer received adjuvant chemotherapy of cisplatin + vinorelbine ditartrate regimen. On day 11 after starting the chemotherapy, she presented a left lower leg pain and readmitted. Computed tomography revealed a deep venous thrombosis of the left lower leg and peripheral pulmonary embolism. The symptom and thromboembolism were successfully treated by anticoagulant drug and thrombolytic therapy. Although cisplatin-based chemotherapy is a risk factor of venous thromboembolism in patients with advanced malignancy, it should be also recognized as a complication of the adjuvant chemotherapy after surgery.

Topics: Anticoagulants; Chemotherapy, Adjuvant; Cisplatin; Drug Substitution; Drug Therapy, Combination; Echocardiography; Female; Fibrinolytic Agents; Fondaparinux; Humans; Lung Neoplasms; Middle Aged; Polysaccharides; Pyridines; Thiazoles; Thrombolytic Therapy; Tomography, X-Ray Computed; Treatment Outcome; Urokinase-Type Plasminogen Activator; Venous Thromboembolism

Von Willebrand factor (VWF) serves as a nidus for platelet aggregation and thrombosis. We hypothesize that VWF fibers contribute to the development of venous thromboembolism (VTE) and to metastasis formation. Here, we show that vascular and lymphatic endothelial cells (ECs) express VWF in vitro and release VWF fibers after activation by tumor cell supernatants. In contrast, an ex vivo analysis of primary mouse tumors revealed the presence of VWF fibers in the blood microvasculature but not in lymphatic vessels. Unlike the anticoagulant Fondaparinux, an inhibitor of thrombin generation, the low-molecular-weight heparin (LMWH) Tinzaparin inhibited VWF fiber formation and vessel occlusion in tumor vessels by blocking thrombin-induced EC activation and vascular endothelial growth factor-A (VEGF-A)-mediated VWF release. Intradermal tumor cell inoculation in VWF- and ADAMTS13-deficient mice did not alter lymph node metastases compared with wild type animals. Interestingly, multiple tumor-free distal organs exhibited hallmarks of malignancy-related VTE, including luminal VWF fibers, platelet-rich thrombi and vessel occlusions. Furthermore, ADAMTS13 deficiency, characterized by prolonged intraluminal VWF network lifetimes, resulted in a severely increased number of metastatic foci in an experimental model of hematogenous lung seeding. Treatment with Tinzaparin inhibited tumor-induced release of VWF multimers, impeded platelet aggregation and decreased lung metastasis. Thus, our data strongly suggest a critical role of luminal VWF fibers in determining the occurrence of thrombosis and cancer metastasis. Moreover, the findings highlight LMWHs as therapeutic strategy to treat thrombotic complications while executing anti-metastatic activities.

Topics: Animals; Blood Vessels; Cell Line, Tumor; Cells, Cultured; Endothelial Cells; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Lymphatic Metastasis; Melanoma, Experimental; Mice, Inbred C57BL; Mice, Knockout; Polysaccharides; Tinzaparin; Vascular Endothelial Growth Factor A; Venous Thromboembolism; von Willebrand Factor

Topics: Anticoagulants; Female; Fondaparinux; Humans; Polysaccharides; Pregnancy; Pregnancy Complications, Hematologic; Venous Thromboembolism

Even in the absence of evidence on its long-term efficacy and safety, a number of patients with venous thromboembolism (VTE) receive long-term therapy with fondaparinux alone in everyday practice.. We used the Registro Informatizado de Enfermedad Tromboembólica (RIETE) registry to compare the rate of VTE recurrences and major bleeding at 10 and 90 days in patients with and without cancer. For long-term therapy, fondaparinux was compared with vitamin K antagonists (VKA) in patients without cancer and with low-molecular-weight heparin (LMWH) in those with cancer.. Of 47,378 patients recruited, 46,513 were initially treated with heparin, 865 with fondaparinux. Then, 263 patients (78 with cancer) were treated for at least 3 months with fondaparinux. After propensity-score matching, there were no differences between patients receiving initial therapy with heparin or fondaparinux. Among patients with cancer, there were no differences between fondaparinux and LMWH. Among patients without cancer, the long-term use of fondaparinux was associated with an increased risk of major bleeding (3.24 % vs. 0.95 %, p<0.05).. An unexpected high rate of major bleeding was observed in non-cancer patients treated with long-term fondaparinux. Our small sample does not allow to derive relevant conclusions on the use of fondaparinux in cancer patients.

Topics: Anticoagulants; Female; Fondaparinux; Humans; Male; Middle Aged; Polysaccharides; Treatment Outcome; Venous Thromboembolism

Unfractionated heparin (UFH), low molecular weight heparin or fondaparinux are recommended for venous thromboembolism (VTE) prophylaxis in acutely ill medical patients. There are limited data on the safety of fondaparinux for VTE prophylaxis in ischemic stroke. We examined adverse event frequency in hospitalized patients with ischemic stroke who received VTE prophylaxis with fondaparinux versus UFH.. We performed a propensity score matched analysis on a retrospective cohort of 644 consecutive patients with acute ischemic stroke receiving fondaparinux (n=322) or UFH (n=322) for VTE prophylaxis. Patients who received intravenous tPA and continuous intravenous infusions of UFH were excluded. The primary outcome was major hemorrhage (intracranial or extracranial) and the secondary outcome was total hemorrhage (major and minor hemorrhage) during hospitalization. We also examined the rate of symptomatic VTE.. Mean age of the matched cohort was 71.3±14.1 years, median NIHSS score was 4 (IQR 1-11), median duration of anticoagulant exposure was 5 (IQR 3-8) days, and 98.1% received antiplatelet medications. In the matched cohort, there were less observed major hemorrhages in the fondaparinux group 1.2% (4/322) compared to UFH 3.7% (12/322), but this difference was not significant (OR=0.33, 95% CI 0.08-1.10, p=0.08). There were also no significant differences in total hemorrhage (p=0.15), intracranial hemorrhage (p=0.48), major extracranial hemorrhage (p=0.18) and symptomatic VTE (p=1.00) between the groups.. Fondaparinux is not associated with increased hemorrhagic complications compared with UFH in patients with ischemic stroke. There were low rates of symptomatic VTE in both groups.

Topics: Aged; Anticoagulants; Cohort Studies; Female; Fondaparinux; Heparin; Humans; Male; Polysaccharides; Retrospective Studies; Stroke; Venous Thromboembolism

Topics: Adult; Aged; Aged, 80 and over; Factor Xa; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Middle Aged; Polysaccharides; Venous Thromboembolism

The aim of this study was to examine the safety and efficacy of fondaparinux (FPX) for venous thromboembolism (VTE) prophylaxis after colorectal cancer surgery.. Records of 953 patients with colorectal cancer who underwent resection between 2006 and 2013 were reviewed. Patients were divided into two groups: the FPX group (n = 362), treated with subcutaneous FPX plus intermittent pneumatic compression (IPC) and the IPC group (n = 591), treated with IPC alone. The incidence of symptomatic VTE, major bleeding, minor bleeding, and other postoperative complications were compared using propensity score matching.. Symptomatic VTE occurred only in one patient (0.2%) in the IPC group. In the FPX group, the incidence of major and minor bleeding was 0.55% (2 of 362) and 9.4% (34 of 362), respectively. After propensity score matching, there were no differences between the two groups in the incidence of symptomatic VTE, major bleeding, and other common postoperative complications. Only the incidence of minor bleeding was significantly higher in the FPX group compared to the IPC group.. FPX is potentially an effective form of VTE prophylaxis; it is safe in terms of both postoperative bleeding and other common complications after colorectal cancer surgery.

Topics: Adult; Aged; Anticoagulants; Colorectal Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Female; Fondaparinux; Humans; Incidence; Intermittent Pneumatic Compression Devices; Male; Matched-Pair Analysis; Middle Aged; Polysaccharides; Postoperative Complications; Postoperative Hemorrhage; Propensity Score; Retrospective Studies; Treatment Outcome; Venous Thromboembolism

Venous thromboembolism (VTE) is a serious threat for all cancer patients. This study was aimed to assess the VTE treatment of cancer patients in the ambulatory care setting.. This is a prospective non-interventional study, which includes ambulatory cancer patients from office-based oncologists. A standardized case report form was used to obtain data on patient characteristics, treatment regimens, duration of treatment, and side effects.. Specialists from 34 centers included data from 76 patients. The median patient age was 62 years (range 33-81 years). The 4 most common cancer types were breast cancer (32%), colorectal cancer (18%), lymphoma and lung cancer (each 8%). 18% of the acute VTE cases were treated as inpatients, 80% as outpatients, and 99% with low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux. After the acute phase, secondary prophylaxis with LMWH/UFH/fondaparinux was planned in 61% of the patients, with oral anticoagulation in 39%. During acute-phase treatment and secondary prophylaxis, no patient had recurrent VTE. 4 patients (5%) experienced minor bleedings.. This study shows that many ambulatory cancer patients with VTE have early tumors, no metastases, and an excellent performance score. Most patients receive LMWHs for secondary prophylaxis, as recommended by the national and international guidelines. Still, a relevant percentage is switched to oral anticoagulants. © 2015 S. Karger GmbH, Freiburg.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Breast Neoplasms; Colorectal Neoplasms; Female; Fondaparinux; Germany; Guideline Adherence; Heparin; Heparin, Low-Molecular-Weight; Humans; Lung Neoplasms; Lymphoma; Male; Middle Aged; Neoplasms; Polysaccharides; Prospective Studies; Recurrence; Surveys and Questionnaires; Venous Thromboembolism

To evaluate the average duration of in-hospital treatment with fondaparinux 2.5mg prescribed for venous thromboprophylaxis in acutely ill medical patients and to describe the treatment population.. Prospective, observational, national, multicentre, epidemiological study, performed in France at the request of the Transparency Commission of the French National Health Authority (Haute Autorité de Santé). This is part of a larger study program that also included a study with similar design in the general practice setting. The hospital practice part of the study was conducted by hospital pharmacists who were asked to include the first 15 adult subjects hospitalized in a non-surgical ward for whom fondaparinux 2.5mg was initiated for prophylaxis.. Fifty-three pharmacists (49.5%) included a total of 718 patients. The average age was 71 ± 16 years (47%<75 years old); 54% were women. For 41% of patients, duration of fondaparinux 2.5mg administration ranged from 6 to 14 days. Eighty-five percent of patients had at least one acute illness related to the prescription of fondaparinux 2.5mg for thromboprophylaxis. Ten percent of the population had at least one risk factor listed on the Case Report Form. Characteristics of patients from the hospital practice study differ from those included in the general practice part of the ArchiMed Study program.. The hospital practice part of the ArchiMed Study, which is similar to "audits of practices", shows that the real-life conditions of prescription of fondaparinux 2.5mg in patients hospitalized are generally in line with guidelines with respect to indication for thromboprophylaxis in acute medical illness.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Bed Rest; Body Mass Index; Creatinine; Diagnosis-Related Groups; Drug Utilization; Female; Fondaparinux; France; Hemorrhage; Hospital Departments; Humans; Length of Stay; Male; Middle Aged; Pharmacy Service, Hospital; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Prospective Studies; Risk Factors; Socioeconomic Factors; Thrombophilia; Venous Thromboembolism; Young Adult

To evaluate the mean duration of treatment course with fondaparinux 2.5 mg (ARIXTRA(®)) in the setting of ambulatory general medicine, with respect to its indication in thromboprophylaxis for medically ill patients and to describe the population treated.. Observational, prospective, national, multicenter, pharmaco-epidemiological study, performed in France, at the request of the Transparency Commission (a division of the French Health Regulatory Authority). The general practitioners had to include the first three adult patients, considered as patients at high risk of venous thromboembolic events and immobilized for acute medical illness, treated with initiation of thromboprophylaxis by fondaparinux 2.5 mg.. Two hundred and seventeen general practitioners included 840 patients. The mean age of patients was 63.6±18.1 years, and 63% of patients (n=520/831) were females. The real total administration duration of the treatment by fondaparinux 2.5 mg was known for 797 patients and was 15.8±12.4 days on average (range: 1-90 days, median: 10 days). In 40% of patients, the duration ranged from 6 to 14 days [duration consistent with the summary of product characteristics (SmPC)]. Among the 834 patients analyzed, 569 (68%) suffered from at least one acute illness and had at least one risk factor for venous thromboembolism (VTE). The indication did fully comply with the summary of product characteristics of fondaparinux 2.5 mg in 52% of the patients (n=434/834 patients).. The results of the ArchiMed study support that the thromboprophylaxis treatment with fondaparinux 2.5 mg in ambulatory general medicine, and the associated medical conditions were usually consistent with the SmPC or guidelines. However, a difference was found for the duration and the initial indication, in situations that may be regarded as presenting a risk by the prescriber.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Back Pain; Bed Rest; Creatinine; Factor Xa Inhibitors; Female; Fondaparinux; General Practice; Humans; Immobilization; Male; Middle Aged; Polysaccharides; Practice Guidelines as Topic; Risk Factors; Surveys and Questionnaires; Thrombophilia; Time Factors; Treatment Outcome; Venous Thromboembolism; Wounds and Injuries; Young Adult

to assess the current use of anticoagulants and implementation of International Guidelines in venous thromboembolism (VTE) prophylaxis in hospitalized patients with acute medical illnesses in Jakarta, Indonesia.. a multicenter, prospective, disease registry, recruiting patients diagnosed as acutely ill medical diseases and other medical conditions at risk of VTE, with in-hospital immobilization for at least 3 days.. of 401 patients, 46.9% received anticoagulants which included unfractionated heparin (64.4%), fondaparinux (11.7%), enoxaparin (9.6%), warfarin (3.7%), and combination of anticoagulants (10.6%). VTE prophylaxis using physical and mechanical method was used in 81.3% of patients, either as a single modality or in combination with anticoagulants. During hospitalization, VTE were found in 3.2% patients; 10 patients (2.5%) had lower limb events and 3 patients (0.75%) had a suspected pulmonary embolism. The main reference international guidelines used were AHA/ASA 2007 (47.4%), followed by ACCP 2008 (21.7%).. the study showed underutilization of prophylaxis anticoagulants in which mechanical thromboprophylaxis either alone or combination with anticoagulants was the most commonly used. Unfractionated heparin was the preferable choice. The most commonly used guideline was AHA/ASA 2007. VTE thromboprophylaxis in medically ill patients needs to be encouraged.

Topics: Acute Disease; Aged; Anticoagulants; Drug Therapy, Combination; Enoxaparin; Female; Fondaparinux; Heparin; Hospitalization; Humans; Indonesia; Male; Middle Aged; Polysaccharides; Practice Guidelines as Topic; Prospective Studies; Risk Factors; Venous Thromboembolism; Warfarin

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer.

Topics: Adult; Anticoagulants; Body Mass Index; Body Weight; Dalteparin; Enoxaparin; Fondaparinux; Heparin; Humans; Neoplasms; Obesity; Polysaccharides; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Venous Thromboembolism

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

The purpose of this prospective study was to evaluate the utility of preferential application of pharmacoprophylaxis based on the quantitative evaluation by soluble fibrin (SF) and plasminogen activator inhibitor-1 (PAI-1) analysis on the day after total hip arthroplasty (THA).. A hundred and sixteen patients were enrolled. High-risk patients were defined as those with elevated levels of SF or PAI-1, beyond their cut-off values, on the day after THA. For high-risk patients, fondaparinux was administered for 10 days postoperatively. When both plasma levels of SF and PAI-1 were less than their cutoff levels, the patients were regarded to be at low risk. For low-risk patients, only mechanical prophylaxis was applied.. Sixty patients (52%) were considered to be at high risk. Among them, venous thromboembolism (VTE) was detected in five patients (8%) by CT angiography. In addition, there were four patients (3%) who developed bleeding complications. Fifty-six patients (48%) were considered to be at low risk, and only one patient (2%) developed VTE.. The measurement of SF and PAI-1 levels on the day after surgery may be helpful to identify the individual risk for postoperative VTE. According to this evaluation, a half of patients might not need to administer anticoagulant agents following surgery.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Female; Fibrin; Fondaparinux; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Polysaccharides; Prospective Studies; Risk Assessment; Treatment Outcome; Venous Thromboembolism

Recurrent venous thromboembolism (VTE) occurs in some patients despite treatment with the standard drugs, warfarin and low-molecular-weight heparin (LMWH). Fondaparinux is currently licensed by the Food and Drug Administration for the prophylaxis of deep-vein thrombosis in patients undergoing orthopedic or abdominal surgery and also in the treatment of VTE. Well-documented use of this agent beyond these indications and for prolonged periods is currently limited.. Two cases of "refractory" VTE, managed effectively with long-term fondaparinux are described. In the first case, a 43-year-old man developed recurrent thrombosis while receiving warfarin at a higher target international normalized ratio (INR) of 3 to 4. In the second case, a 45-year-old man developed recurrent thrombosis on once-daily dalteparin. Both the patients were successfully managed with fondaparinux for 36 months and 14 months, respectively, with no sign of recurrent thrombosis or adverse effects.. In patients with recurrent VTE, fondaparinux is effective as daily injections as much as twice-daily LMWH or warfarin maintained on higher therapeutic-range INRs. Although the exact mechanism for this effectiveness is not yet understood, it provides a useful alternative to the standard therapies. In addition, the side effect profile is also favorable for fondaparinux, in that it causes less thrombocytopenia and skin reactions in comparison with heparins.. Daily fondaparinux injections may be an effective antithrombotic agent in patients who develop recurrent VTE on anticoagulation with warfarin or LMWH.

Topics: Adult; Anticoagulants; Dalteparin; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Injections, Subcutaneous; Male; Middle Aged; Polysaccharides; Recurrence; Thrombocytopenia; Venous Thromboembolism; Warfarin

Hospitalised patients with inflammatory bowel disease are 1.5- to 3.5-fold more likely to develop venous thromboembolism compared to controls. Clinical guidelines recommend pharmacological prophylaxis.. To determine the rate of pharmacological venous thromboembolism prophylaxis prescription and administration in a cohort of hospitalised patients with severe active ulcerative colitis and to assess predictors of failure to order pharmacological prophylaxis at 24 h.. This is a retrospective review of hospitalised patients with severe active ulcerative colitis, identified by ICD-9-CM discharge code 556.x, admitted to a single tertiary care hospital from 1 January 2005 to 31 August 2012. Adequate thromboembolism prophylaxis was defined as an order for low-dose unfractionated heparin two to three times daily, low-molecular weight heparin 40 mg daily or fondaparinux 2.5 mg daily ordered and administered for >80% of the admission. Patient related factors associated with failure to order prophylaxis at 24 h were accessed as secondary outcomes.. Three hundred and thirty-six patients were hospitalised with severe active ulcerative colitis. Hospitalists had prescribed appropriate pharmacological prophylaxis by 48 h in only 37% of cases. Of these, nurses administered all prescribed doses in 18% of cases. Only 7% of patients (22/304, 95% CI: 5-11%) received adequate pharmacological prophylaxis for >80% of their hospitalisation. Hematochezia (P = 0.002), elevated platelets (P = 0.008), male gender coupled with younger age (P = 0.005) and admission on a biologic (P = 0.03) were associated with failure to order prophylaxis.. Hospitalised patients admitted with severe active ulcerative colitis are not receiving appropriate pharmacological venous thromboembolism prophylaxis.

Topics: Adult; Anticoagulants; Colitis, Ulcerative; Female; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Male; Middle Aged; Polysaccharides; Practice Guidelines as Topic; Retrospective Studies; Severity of Illness Index; Venous Thromboembolism

Thromboprophylaxis is recommended for preventing postoperative venous thromboembolism (VTE) after abdominal surgery; however, its use after major hepatobiliary-pancreatic surgery is typically avoided as it increases the risk of bleeding. We conducted this study to evaluate the safety of thromboprophylaxis after major hepatobiliary-pancreatic surgery.. We analyzed the rates of postoperative bleeding, VTE, morbidity, and prolonged hospital stay in 349 patients who underwent major hepatobiliary-pancreatic surgery, such as pancreaticoduodenectomy, hemihepatectomy or greater, and hepatopancreaticoduodenectomy.. Chemical thromboprophylaxis was associated with significantly increased rates and risks of overall bleeding events vs. no chemical thromboprophylaxis (26.6 vs. 8.5%, respectively). The rate of minor hemorrhage was significantly higher in patients who received chemical thromboprophylaxis (21.7 vs. 3.5%); however, there were no differences in the rate of major hemorrhage requiring blood transfusion or hemostatic intervention between the groups (4.8 vs. 4.9%). The postoperative VTE rate was also significantly decreased by chemical thromboprophylaxis (2.9 vs. 7.7%). However, chemical thromboprophylaxis did not affect the rate of SSI, severe morbidity, or duration of the postoperative hospital stay.. We consider that chemical thromboprophylaxis is beneficial and can be safely used even after major hepatobiliary-pancreatic surgery.

Topics: Aged; Anticoagulants; Asian People; Enoxaparin; Female; Fondaparinux; Hemorrhage; Hepatectomy; Humans; Length of Stay; Male; Middle Aged; Morbidity; Pancreaticoduodenectomy; Polysaccharides; Postoperative Complications; Risk; Safety; Treatment Outcome; Venous Thromboembolism

To investigate the safety and efficacy of fondaparinux (FPX) for venous thromboembolism (VTE) prophylaxis in Japanese patients undergoing colorectal cancer surgery.. The subjects of this multicenter, open-label, prospective observational study were patients undergoing resection of the colon/rectum for colorectal cancer. All patients were given FPX 2.5 or 1.5 mg by subcutaneous injection, once daily for 4-8 days, starting 24 h after surgery. The primary endpoint was any major bleeding event and the secondary endpoint was any symptomatic VTE event.. Between February 2009 and December 2010, 619 patients from 23 institutions were enrolled in this study. The median duration of FPX prophylaxis was 4 days. The incidence of major bleeding was 0.81 % [5/619, 95 % confidence interval (CI) 0.3-1.9] and the incidence of minor bleeding was 9.5 % (59/619, 95 % CI 7.3-12.1). There was no fatal bleeding or symptomatic VTE. Multivariable analysis revealed the following to be risk factors for bleeding events: preoperative platelet count <15 × 10(4)/µl [odds ratio (OR) 4.521], male sex (OR 2.078), and blood loss during surgery <50 ml (OR 2.019).. The administration of 2.5/1.5 mg FPX 24 h after colorectal cancer surgery is safe and effective.

Topics: Aged; Anticoagulants; Asian People; Colorectal Neoplasms; Female; Fondaparinux; Humans; Injections, Subcutaneous; Male; Middle Aged; Polysaccharides; Postoperative Complications; Premedication; Prospective Studies; Safety; Time Factors; Treatment Outcome; Venous Thromboembolism

To analyze clinical characteristics of venous thromboembolisms (VTE) in gynecological malignancies, and to find a cost-effective prophylaxis procedure for post-operative VTE.. We analyzed clinical characteristics of 751 patients who underwent definitive surgery for gynecologic malignancies, and cost-effectiveness of VTE prophylaxis.. VTE was diagnosed preoperatively in 4.5% of ovarian cancer cases, more frequently than any other type (p<0.005). Older age and greater length of operation were independent risk factors for postoperative VTE. To prevent eight VTEs in 738 malignant cases, which occurred during day 2 to 10, $617,783, $726,185, or $994,222 were necessary for continuous VTE prophylaxis, using either unfractionated heparin (UFH), low-molecular weight heparin or fondaparinux, respectively.. A strategy which might be cost-effective for post-surgical management of gynecological malignances is use of UFH three times combined with graduated compression stockings and intermittent pneumatic compression, thorough SpO2 monitoring, and perioperative measurements of the circumference of both sides of thighs and calves.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Cost-Benefit Analysis; Female; Fondaparinux; Genital Neoplasms, Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Japan; Middle Aged; Perioperative Period; Polysaccharides; Venous Thromboembolism

Venous thromboembolism (VTE) is one of the leading causes of morbidity and mortality in acutely ill medical patients. Fondaparinux is recommended for the prevention of VTE in this setting, but little information is available on its safety and effectiveness in unselected, "real world" patients. The aim of this paper was to assess the safety and efficacy of fondaparinux in elderly acutely ill medical patients.. Single center, retrospective study. All patients >60 years, admitted for acute medical disease, bedridden for at least four days and treated with fondaparinux were evaluated. Occurrence of objectively documented, symptomatic VTE, and of bleeding events during the treatment period and follow-up were reported.. Two hundred and ten patients (median age 81 years) were treated with fondaparinux. Seventy patients received fondaparinux 1.5 mg daily, 140 received the 2.5 mg daily dose. However, 29 patients in the first group (with a CrCl≥50 mL/min) and 84 patients in the last group (with a CrCl<50 mL/min) did not receive the correct dose of fondaparinux. During treatment, one episode (0.48%, 95% CI 0.1% to 2.6%) of major bleeding and 6 episodes (2.86%, 95% CI 1.3% to 6.1%) of clinically relevant non major bleeding were recorded. Only one thromboembolic event (0.48%, 95% CI 0.1% to 2.6%) was documented. Thirty-nine patients died; no death was related to VTE, unlike one death was due to major bleeding. Cancer was the only significant predictor of bleeding at statistical analysis.. In elderly acutely ill hospitalized medical patients, thromboprophylaxis with fondaparinux 2.5 or 1.5mg daily is safe and effective in preventing VTE without increasing bleeding risk.

Topics: Acute Disease; Aged; Aged, 80 and over; Anticoagulants; Drug Administration Schedule; Female; Fondaparinux; Hemorrhage; Humans; Incidence; Inpatients; Italy; Male; Medical Records; Polysaccharides; Renal Insufficiency, Chronic; Retrospective Studies; Venous Thromboembolism

The incidence of venous thrombotic events (VTE) and use of anticoagulants in children have both risen over time. It is imperative that safety and efficacy studies of newer anticoagulants include children.. The purpose of this study was to investigate the long-term safety, dosing, and efficacy of fondaparinux in children.. The study included children 1-18 years old treated with fondaparinux at Children's Hospital Los Angeles. Descriptive statistics were used to present our findings.. Data from 35 patients were collected and analyzed. Fourteen of 22 evaluable patients (63.6%) had complete resolution of their thrombus, 6/22 (27.3%) had partial resolution, and 2/22 (9.1%) had no change. Ten patients needed a total of 16 dose adjustments over a median 152 days treatment duration to achieve therapeutic levels. Two patients (9.1%) had VTE recurrence. There were 3 major (intracranial hemorrhage- prior to initiation of fondaparinux, pulmonary hemorrhage, and subretinal hemorrhage) and 6 minor (2 with blood in stool, 1 with injection site, 1 CVC site, 1 tracheostomy bleed, 1 epistaxis) bleeding events.. In this long-term follow-up study on children treated with fondaparinux for VTE, 90.9% of patients had either complete or partial resolution while the recurrence rate was in line with previous studies. There were 9 bleeding events (3 major and 6 minor), though only 1 event required the discontinuation of fondaparinux. Given the advantages of fondaparinux over other anticoagulants, this study suggests that fondaparinux could be considered a safe and effective alternative for the management of VTE in children.

Topics: Adolescent; Age Factors; Anticoagulants; Child; Child, Preschool; Drug Administration Schedule; Drug Dosage Calculations; Female; Follow-Up Studies; Fondaparinux; Hemorrhage; Hospitals, Pediatric; Humans; Infant; Los Angeles; Male; Polysaccharides; Prospective Studies; Recurrence; Retrospective Studies; Time Factors; Treatment Outcome; Venous Thromboembolism

Topics: Anticoagulants; Cardiology; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hospitalization; Humans; International Cooperation; Neoplasms; Polysaccharides; Renal Insufficiency; Societies, Medical; Thrombocytopenia; Venous Thromboembolism

Venous thromboembolism (VTE) causes significant morbidity and mortality in surgical patients. Despite strong evidence that thromboprophylaxis reduces the incidence VTE, guidelines for prophylaxis in otolaryngology are not well established. Key to the development of VTE prophylaxis recommendations are effective VTE risk stratification and evaluation of the benefits and harms of prophylaxis.. To evaluate the effectiveness and safety of VTE chemoprophylaxis among a population of otolaryngology patients stratified by risk.. Retrospective cohort study of 3498 adult patients admitted for otolaryngologic surgery at a single-institution academic tertiary care medical center between September 1, 2003, and June 30, 2010.. Patients were stratified into 2 groups based on whether they received VTE chemoprophylaxis.. Incidence of VTE and bleeding-related complications within 30 days after surgery.. Of 1482 patients receiving VTE chemoprophylaxis, 18 (1.2%) developed a VTE compared with 27 of 2016 patients (1.3%) who did not receive prophylaxis (P = .75). Patients with Caprini VTE risk scores greater than 7 were less likely to have a VTE with perioperative chemoprophylaxis (5.3% vs 10.4%; P = .06). Of patients with VTE chemoprophylaxis, 3.5% developed a bleeding complication compared with 1.2% of patients without prophylaxis (P < .001). Bleeding complications were associated with concomitant use of antiplatelet medications and chemoprophylaxis. Among patients undergoing free tissue transfer, chemoprophylaxis significantly decreased the incidence of VTE (2.1% vs 7.7%; P = .002) and increased bleeding complications (11.9% vs 4.5%; P = .01). In all other patients, VTE chemoprophylaxis did not significantly influence the likelihood of VTE (1.0% vs 0.6%; P = .12) or bleeding (1.5% vs 0.9%; P = .15).. Effectiveness and safety of VTE chemoprophylaxis differed between patient subgroups, defined by Caprini risk score and by procedure. Effectiveness was most evident in patients with high Caprini risk scores and microvascular free tissue reconstruction. Bleeding complications were associated with VTE chemoprophylaxis administered in close proximity to potent antiplatelet therapy. The Caprini risk assessment model appears to be an effective tool to stratify otolaryngology patients by risk for VTE. Patients undergoing free tissue reconstruction merit further study before developing recommendations for VTE prophylaxis because of their higher risk of both VTE and bleeding.

Topics: Anticoagulants; Enoxaparin; Fondaparinux; Free Tissue Flaps; Hemorrhage; Heparin; Humans; Incidence; Otolaryngology; Otorhinolaryngologic Surgical Procedures; Polysaccharides; Retrospective Studies; Risk Assessment; Venous Thromboembolism

Inflammatory bowel disease (IBD) patients are at increased risk of venous thromboembolism (VTE) especially during hospitalization. We assessed the safety and predictors of VTE prophylaxis in this population.. We conducted a retrospective study of 974 IBD admissions between February 2010 and May 2012. We abstracted data on clinical characteristics, VTE prophylaxis and bleeding events, and conducted multivariate analysis to determine predictors of prophylaxis.. Pharmacological VTE prophylaxis was administered to 80% of admissions; 63% were within 24h of admission. Patients on the surgical service (adjusted OR [aOR], 3.82; 95% CI: 2.00-7.29) and general medicine (aOR, 2.40; 95% CI: 1.39-4.12) were more likely to receive VTE prophylaxis compared to those on the gastroenterology service. Rectal bleeding on admission was associated with lower prophylaxis (aOR, 0.58; 95% CI: 0.35-0.97). The VTE prophylaxis rate increased from 47% to 73% (P<0.001) on non-surgical services with the introduction of a pharmacist advocate. The rates of major and minor bleeding were similar between patients who did and did not receive VTE prophylaxis (0.26 vs. 0 per 1000 person-days, P=0.7; 4.18 vs. 2.53 per 1000 person-days, P=0.4 respectively), and the major bleeding events (n=2) were post-operative. VTE prophylaxis was not associated with major postoperative bleeding (0.4% vs. 0%, P=0.96).. VTE prophylaxis was more frequent on the surgical service, where standardized protocols exist. The introduction of a pharmacist advocate greatly increased VTE prophylaxis on the non-surgical services. Prophylactic anticoagulation is safe in IBD despite the presence of rectal bleeding on admission.

Topics: Adult; Anticoagulants; Contraindications; Female; Fondaparinux; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Hospital Departments; Hospitalization; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Pharmacy Service, Hospital; Polysaccharides; Practice Patterns, Physicians'; Rectum; Retrospective Studies; Venous Thromboembolism; Warfarin; Young Adult

Fondaparinux and enoxaparin are useful for preventing venous thromboembolism after total knee arthroplasty (TKA), but both drugs have associated complications. The purpose of this study was to clarify the risks associated with use of these drugs in Japanese patients who underwent TKA.A total of 575 patients (935 knees) underwent TKA and were retrospectively reviewed; 277 patients (454 knees) were treated with fondaparinux and 298 patients (481 knees) were treated with enoxaparin. The authors investigated the incidences of deep venous thrombosis of the lower limbs and pulmonary embolism to evaluate venous thromboembolism, knee enlargement compared with the preoperative size, incidence of subcutaneous knee hematoma, and other complications. No significant differences were observed between the 2 drugs regarding the incidences of deep venous thrombosis and pulmonary embolism. However, fondaparinux use resulted in knee enlargement (P<.0005) and subcutaneous hematoma of the knee (P=.035) significantly more often than enoxaparin use. Conversely, enoxaparin use significantly caused the elevation of alanine aminotransferase (one of the liver enzymes) at a higher rate than fondaparinux (30.1% vs 8.3%, respectively; P<.0001). However, the increased alanine aminotransferase levels were transient, and no patient exhibited symptoms of abnormal liver function, such as jaundice or cutaneous pruritus.Fondaparinux and enoxaparin were both effective in preventing venous thromboembolism in Japanese patients undergoing elective TKA. However, both drugs had some adverse effects. It is important to be aware of these potential risks when prescribing these drugs.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Female; Fondaparinux; Humans; Joint Diseases; Male; Polysaccharides; Retrospective Studies; Risk Factors; Venous Thromboembolism

Long term anticoagulant therapy is recommended for treatment and secondary prevention of venous thromboembolism in cancer patients. We assessed outpatient anticoagulants [warfarin, low molecular weight heparins (LMWHs), fondaparinux and unfractionated heparin (UFH)] use in adult, cancer patients, 20years of age or older, who incurred a venous thromboembolism (primary or secondary in-hospital diagnosis) in Quebec, Canada between 2007 and 2009.. Data were obtained from the Quebec Health Insurance Agency. Patients with an in-hospital cancer diagnosis between April 2007 and June 2009 and an in-hospital venous thromboembolism diagnosis either concurrently or consequently were eligible at the date of discharge (index date). Those patients registered with the provincial drug plan and discharged to the community were included in the study and followed for 6months.. Among 2,070 study patients, 72.4% received anticoagulant therapy at index date, 60% of whom were persistent with therapy and received it for ≥80% of follow-up days. Outpatient anticoagulant use was more likely in those with primary versus secondary diagnosis of venous thromboembolism and less likely in patients with cerebrovascular disease, peptic ulcer disease or previous anticoagulant use. The small number of patients who used either UFH (n=11) or fondaparinux (n=5) at index date were included in the LMWH group. Warfarin use was less likely than LMWH use in corticosteroid users, previous anticoagulant users, patients with metastatic cancer and those with catheter or chemotherapy in the previous three months. Warfarin use was more likely than LMWH use in: older patients, those residing in rural areas, those with lower income and those suffering from ischemic heart disease, atrial fibrillation or chronic kidney disease. Patients with ischemic heart disease were more likely to have used a non-dalteparin LMWH versus dalteparin (currently, the only LMWH approved by health Canada for chronic treatment of VTE), while those residing in rural areas and those with catheter/chemotherapy were less likely to have used them. A primary (versus secondary) discharge diagnosis of venous thromboembolism [Odds Ratio 1.42; 95% confidence interval (1.14, 1.76)], and metastatic cancer 1.27 (1.00, 1.60) were associated with persistence on anticoagulant treatment.. Guideline recommended outpatient use of anticoagulant in cancer patients hospitalized with venous thromboembolism was influenced by cancer status, old age and low income. Risk factors for bleeding prevented outpatient anticoagulant use in some patients.

Topics: Adult; Aged; Anticoagulants; Cohort Studies; Female; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Odds Ratio; Polysaccharides; Retrospective Studies; Time Factors; Venous Thromboembolism; Warfarin

Many hospitalized medically ill patients are at risk of venous thromboembolism (VTE). Risk factors include prior VTE, older age, immobility, obesity, cardiac or respiratory failure, and cancer (at-risk patients). Although guidelines recommend use of VTE prophylaxis for at-risk patients, many may not receive it.. Using a database linking admission records from >150 US hospitals to health insurance claims, we identified people ≥40 years of age, hospitalized from 2003 to 2008. We excluded patients who: (1) were treated for VTE or hospitalized in the previous 30 days; (2) were admitted for traumatic injury or surgery; (3) had hypercoagulability at admission; or (4) received therapeutic dosages of low-molecular weight heparin, unfractionated heparin, or fondaparinux at admission. We examined the use of VTE prophylaxis (both pharmacological and nonpharmacological) on day 1 or 2 in hospital among at-risk patients; predictors of receipt of prophylaxis were examined using multivariate logistic regression. The study population consisted of 49 948 patients, of whom 34 374 (69%) were at risk. Only 18% of at-risk patients received VTE prophylaxis on day 1 or 2 in hospital, typically with low-molecular weight heparin (56% of patients receiving prophylaxis), intermittent pneumatic compression (25%), warfarin (16%), or graduated compression stockings (11%). Use of prophylaxis exceeded 25% only in patients admitted from nursing homes and those with prior VTE. Although there were several significant predictors of receipt of VTE prophylaxis, model discrimination was relatively poor (C-statistic=0.61).. The majority of at-risk hospitalized medically ill patients do not receive VTE prophylaxis.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Fibrinolytic Agents; Fondaparinux; Guideline Adherence; Heparin; Heparin, Low-Molecular-Weight; Humans; Inpatients; Intermittent Pneumatic Compression Devices; Male; Middle Aged; Polysaccharides; Retrospective Studies; Risk Factors; Societies, Medical; United States; Venous Thromboembolism; Warfarin

Real-life data on post-discharge venous thromboembolism (VTE) prophylaxis practices and treatments are lacking. We assessed post-operative VTE prophylaxis prescribed and received in a prospective registry, compared with the 2004 American College of Chest Physicians (ACCP) guidelines in high-risk orthopaedic surgery patients. Consecutive patients undergoing total hip arthroplasty (THA), hip fracture surgery (HFS), or knee arthroplasty (KA) were enrolled at discharge from 161 centres in 17 European countries if they had received in-hospital VTE prophylaxis that was considered in accordance with the ACCP guidelines by the treating physician. Data on prescribed and actual prophylaxis were obtained from hospital charts and patient post-discharge diaries. Post-operative prophylaxis prescribed and actual prophylaxis received were considered adherent or adequate, respectively, if recommended therapies were used for ≥28 days (HFS and THA) or ≥10 days (KA). Among 4,388 patients, 69.9% were prescribed ACCP-adherent VTE prophylaxis (THA: 1,411/2,217 [63.6%]; HFS: 701/1,112 [63.0%]; KA: 955/1,059 [90.2%]). Actual prophylaxis received was described in 3,939 patients with an available diary after discharge (non-evaluability rate of 10%). Mean actual durations of pharmacological prophylaxis from surgery were: 28.4 ± 13.7 (THA), 29.3 ± 13.9 (HFS), and 28.7 ± 14.1 days (KA). ACCP-adequate VTE prophylaxis was received by 66.5% of patients (60.9% THA, 55.4% HFS, and 88.7% KA). Prophylaxis inadequacies were mainly due to inadequate prescription, non-recommended prophylaxis prescription at discharge, or too short prophylaxis prescribed. In high-risk orthopaedic surgery patients with hospital-initiated prophylaxis, there is a gap between ACCP recommendations, prescribed and actual prophylaxis received, mainly due to inadequate prescription at discharge.

Topics: Aged; Anticoagulants; Europe; Female; Fondaparinux; Guideline Adherence; Heparin, Low-Molecular-Weight; Humans; International Cooperation; Male; Orthopedic Procedures; Patient Discharge; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Registries; Risk; Venous Thromboembolism

Venous thromboembolism (VTE) risk persists for several weeks following high-risk orthopaedic surgery (HROS). The ETHOS registry evaluated post-operative VTE prophylaxis prescribed, and actual VTE prophylaxis received, compared with the 2004 American College of Chest Physicians (ACCP) guidelines in HROS patients. We performed a subanalysis of ETHOS to assess patient compliance with ACCP-adherent prophylaxis after discharge and the factors predicting poor compliance. Consecutive patients undergoing hip fracture surgery, total hip arthroplasty, or knee arthroplasty were enrolled at discharge from 161 centres in 17 European countries if they had received adequate in-hospital VTE prophylaxis. Data on prescribed and actual prophylaxis received were obtained from hospital charts and patient post-discharge diaries. Good compliance was defined as percentage treatment intake ≥80% with no more than two consecutive days without treatment. A total of 3,484 patients (79.4%) received ACCP-adherent anticoagulant prescription at discharge and 2,999 (86.0%) had an evaluable patient diary. In total, 87.7% of evaluable patients were compliant with prescribed treatment after discharge. The most common reason for non-compliance (33.4%) was "drug was not bought". Injection of treatment was not a barrier to good compliance. Main factors affecting compliance related to purchase of and access to treatment, patient education, the person responsible for administering injections, country, and type of hospital ward at discharge. Within our study population, patient compliance with ACCP-adherent thromboprophylaxis prescribed at discharge was good. Improvements in patient education and prescribing practices at discharge may be important in further raising compliance levels in high-risk orthopaedic surgery patients.

Topics: Adult; Aged; Anticoagulants; Cost of Illness; Drug Utilization Review; Europe; Female; Fondaparinux; Guideline Adherence; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Orthopedic Procedures; Patient Compliance; Patient Discharge; Polysaccharides; Postoperative Complications; Registries; Risk; Venous Thromboembolism

Markers of coagulation and fibrinolysis, such as soluble fibrin (SF), D-dimer, and plasminogen activator inhibitor 1 (PAI-1), have been developed in order to determine thrombotic tendency. We investigated whether these markers could be used to diagnose venous thromboembolism (VTE) in the early phase after primary total hip arthroplasty (THA).. This prospective study involved 2 groups: an intermittent pneumatic compression (IPC) group (67 patients who underwent IPC only as prophylaxis for VTE) and a fondaparinux (FPX) group (103 patients who received IPC and FPX postoperatively). Plasma levels of SF and PAI-1 were measured on postoperative day 1. To diagnose postoperative VTE, multi-detector row computed tomography (MDCT) and duplex ultrasonography (US) were performed on postoperative day 7.. VTE was detected postoperatively in 17 cases in the IPC group (25%) and in 8 cases in the FPX group (6%). In the IPC group, plasma levels of SF and PAI-1 were higher in patients with VTE (p < 0.01) than in those without VTE. On the other hand, in the FPX group there were no differences in the levels of SF or PAI-1 measured before administration of FPX on postoperative day 1. The diagnostic criterion of an increase in SF or PAI-1 above the cutoff level (19.8 µg/mL and 53.5 ng/mL, respectively) provided a sensitivity of 100% and a specificity of 67% in the IPC group. In addition, when this criterion was applied to FPX patients, 7 of the 8 patients with VTE met the criterion, and there was a negative agreement rate of 48/49.. Screening using the cutoff levels of SF and PAI-1 may be useful and shows high sensitivity in predicting postoperative VTE in the early phase after THA.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombin III; Arthroplasty, Replacement, Hip; Biomarkers; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fondaparinux; Humans; Male; Middle Aged; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Polysaccharides; Primary Prevention; Prospective Studies; Risk Assessment; Risk Factors; Treatment Outcome; Venous Thromboembolism

This guideline addressed VTE prevention in hospitalized medical patients, outpatients with cancer, the chronically immobilized, long-distance travelers, and those with asymptomatic thrombophilia.. This guideline follows methods described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.. For acutely ill hospitalized medical patients at increased risk of thrombosis, we recommend anticoagulant thromboprophylaxis with low-molecular-weight heparin (LMWH), low-dose unfractionated heparin (LDUH) bid, LDUH tid, or fondaparinux (Grade 1B) and suggest against extending the duration of thromboprophylaxis beyond the period of patient immobilization or acute hospital stay (Grade 2B). For acutely ill hospitalized medical patients at low risk of thrombosis, we recommend against the use of pharmacologic prophylaxis or mechanical prophylaxis (Grade 1B). For acutely ill hospitalized medical patients at increased risk of thrombosis who are bleeding or are at high risk for major bleeding, we suggest mechanical thromboprophylaxis with graduated compression stockings (GCS) (Grade 2C) or intermittent pneumatic compression (IPC) (Grade 2C). For critically ill patients, we suggest using LMWH or LDUH thromboprophylaxis (Grade 2C). For critically ill patients who are bleeding or are at high risk for major bleeding, we suggest mechanical thromboprophylaxis with GCS and/or IPC at least until the bleeding risk decreases (Grade 2C). In outpatients with cancer who have no additional risk factors for VTE we suggest against routine prophylaxis with LMWH or LDUH (Grade 2B) and recommend against the prophylactic use of vitamin K antagonists (Grade 1B).. Decisions regarding prophylaxis in nonsurgical patients should be made after consideration of risk factors for both thrombosis and bleeding, clinical context, and patients' values and preferences.

Topics: Ambulatory Care; Combined Modality Therapy; Critical Care; Evidence-Based Medicine; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hospitalization; Humans; Immobilization; Intermittent Pneumatic Compression Devices; Neoplasms; Polysaccharides; Randomized Controlled Trials as Topic; Risk Factors; Societies, Medical; Stockings, Compression; Travel; Venous Thromboembolism

Fondaparinux, a selective activator factor X (factor Xa) inhibitor, is effective and safe for preventing venous thromboembolism after major orthopaedic surgery (MOS) at the once-daily subcutaneous dose of 2.5 mg. As the drug is mainly eliminated by the kidneys, a reduced dosage (1.5 mg once daily) was developed for patients with renal impairment.. We studied the pharmacokinetics (PK) of this dosage regimen using data from a real-world cohort of 442 patients with renal impairment (creatinine clearance 20-50 ml/min) undergoing MOS. Data were analysed using NON-linear Mixed Effect Modelling software (NONMEM) software. Fondaparinux PK was modelled using a two-compartment model with first-order absorption.. This analysis confirmed the relationship between renal function and fondaparinux PK profiles. The mean predicted steady-state area under the plasma concentration time curve, peak and trough plasma concentrations of fondaparinux were lower by 15.6 %, 13.0 % and 10.3 %, respectively, in patients with renal impairment treated with 1.5 mg compared with patients with normal renal function treated with 2.5 mg (p < 0.01).. Although administration of 1.5 mg fondaparinux in patients with renal impairment resulted in a predicted exposure slightly lower than that achieved with 2.5 mg in patients with normal renal function, fondaparinux 1.5 mg is a valuable thromboprophylactic option in MOS patients with renal impairment who are at risk of bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Area Under Curve; Cohort Studies; Drug Administration Schedule; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Kidney; Male; Orthopedic Procedures; Polysaccharides; Renal Insufficiency; Venous Thromboembolism

Despite the need for effective and safe thromboprophylactic drugs for patients with renal impairment, clinical trial data on anticoagulant agents are limited in this population. The study aim was to assess in the real-world setting the use of the once-daily 1.5 mg reduced dosage regimen of fondaparinux available for this context. In this prospective cohort study, patients with a creatinine clearance (CrCl) of 20-50 ml/minute, undergoing total hip (THR) or knee (TKR) replacement or hip fracture surgery (HFS) received fondaparinux thromboprophylaxis. Main clinical outcomes were bleeding (major/clinically relevant non-major), symptomatic venous thromboembolism (VTE) and death. Overall, 442 patients (353 women; median age: 82 years; 39.4% in ASA class ≥3; mean ± SD CrCl: 39.0 ± 8.0 ml/minute; 78% with additional risk factors for bleeding), undergoing THR (43.7%), TKR (27.6%), or HFS (28.7%) received fondaparinux 1.5 mg for a mean ± SD duration of 16.0 ± 12.5 days. At postoperative day 10, the rates (95% confidence interval) of major bleeding, clinically relevant bleeding and symptomatic VTE were 4.5% (2.8-6.9), 0.5% (0.1-1.6) and 0.5% (0.05-1.62), respectively; no fatal bleeding, bleeding into a critical organ, pulmonary embolism or proximal deep-vein thrombosis occurred. Corresponding rates at one month were 5.2%, 0.7% and 0.7%. One-month mortality was 2.3% (0.9-3.6). This large clinical prospective study provides for the first time, under conditions reflecting "real-world" routine clinical practice, data on the bleeding and VTE risks of thromboprophylaxis with fondaparinux 1.5 mg after major orthopaedic surgery in renally impaired patients. It shows that these patients constitute a very elderly and fragile population.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Biomarkers; Creatinine; Female; Fondaparinux; Fracture Fixation; France; Hemorrhage; Hip Fractures; Humans; Kidney; Logistic Models; Male; Middle Aged; Multivariate Analysis; Orthopedic Procedures; Polysaccharides; Prospective Studies; Renal Insufficiency; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Venous Thromboembolism

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

To describe the course and management of thrombotic storm in 8 children.. Clinical data were collected and analyzed for consecutive children diagnosed with thrombotic storm, aged 6 months to 21 years inclusive, in the context of a single-institution prospective inception cohort study. Thrombotic storm was defined as newly diagnosed multisite venous thromboembolism (VTE) with acute thrombus progression despite conventional or higher than conventional dosing of heparin or low molecular weight heparin. All evaluations and therapies were ordered by the treating physicians in the context of clinical decision making.. Eight of the 178 children with VTE enrolled in the cohort between March 2006 and November 2009 were diagnosed with thrombotic storm. Antiphospholipid antibodies were acutely positive in 6 children, of whom heparin-induced thrombocytopenia was confirmed by serotonin release assay in 2 and atypical in 1. One child died. Five children received a direct thrombin inhibitor, titrated to achieve normalization of markedly elevated D-dimer levels. All children were transitioned to fondaparinux or enoxaparin before receiving extended anticoagulation with warfarin. Immunomodulatory therapy was instituted in all children. During follow-up (median duration, 3 years; range, 2-6 years), 3 of the 7 surviving children experienced recurrent VTE, and 4 children had clinically significant postthrombotic syndrome.. Thrombotic storm is an infrequent but potentially fatal presentation of VTE in children. Administration of direct thrombin inhibitors and immune modulation can achieve quiescence, although long-term adverse outcomes are common.

Topics: Adolescent; Anticoagulants; Antiphospholipid Syndrome; Child; Child, Preschool; Cytokines; Enoxaparin; Fatal Outcome; Female; Fondaparinux; Humans; Immunomodulation; Male; Polysaccharides; Prospective Studies; Venous Thromboembolism; Young Adult

Controversy exists regarding the optimal preventative therapy for venous thromboembolism (VTE) after coronary artery bypass graft (CABG) surgery. We sought to compare the effectiveness and safety of the most commonly used regimens.. We assembled a cohort of 92 699 patients who underwent CABG between 2004 and 2008, using the Premier database. Patients were categorized by method of VTE prevention initiated within 48 hours of surgery, including no preventative therapy (n=55 400), mechanical preventative therapy (n=21 162), subcutaneous unfractio--nated or low-molecular-weight heparin (n=10 718), subcutaneous fondaparinux (n=88), and concurrent mechanical-chemical therapy (n=5331). The incidence of VTE and major bleeding events within 6 weeks of CABG were compared, using multivariable and propensity score adjustment. The overall incidence of VTE for the entire cohort was 0.74%, and the incidence of major bleeding was 1.43%. VTE and bleeding events occurred with similar incidence in each of the patient categories (VTE: 0.70%, 0.79%, 0.81%, 1.14%, and 0.73%; major bleeding: 1.36%, 1.45%, 1.69%, 3.41%, 1.50%; no prevention, mechanical prevention, subcutaneous heparin, subcutaneous fondaparinux, concurrent mechanical-chemical prevention, respectively). Compared with receiving no prevention, the use of mechanical prevention or subcutaneous heparin did not significantly reduce the risk of VTE or change the risk of major bleeding (P=NS).. Venous thromboembolism occurs infrequently after CABG. Compared with the use of no prevention, the administration of chemical or mechanical preventative therapies to CABG patients does not appreciably lower the risk of VTE. These data provide support for the common practice of administering no VTE preventative therapy after CABG, used for nearly 60% of patients within this cohort.

Topics: Aged; Anticoagulants; Cohort Studies; Comorbidity; Coronary Artery Bypass; Databases, Factual; Female; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Polysaccharides; Postoperative Complications; Risk Factors; Stockings, Compression; Venous Thromboembolism

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

Thromboprophylaxis with rivaroxaban (R) is superior to enoxaparin in patients undergoing major orthopedic surgery (MOS). However, rivaroxaban has never been directly compared with fondaparinux (F), which also shows superior efficacy over enoxaparin. The clinical impact of switching from fondaparinux to rivaroxaban thromboprophylaxis is unclear.. To evaluate the efficacy and safety of rivaroxaban or fondaparinux thromboprophylaxis in unselected patients undergoing MOS.. This is a monocentric, retrospective cohort study in 5061 consecutive patients undergoing MOS at our centre, comparing rates of symptomatic VTE, bleeding and surgical complications, length of hospital stay and risk factors for VTE.. Rates of symptomatic VTE were 5.6% (F) and 2.1% (R; P < 0.001), with rates for distal DVT being 3.9 vs. 1.1% (P < 0.001). Rates of major VTE were numerically higher with fondaparinux (1.8 vs. 1.1%), but not statistically significant. Rates of severe bleeding (bleeding leading to surgical revision or death, occurring in a critical site, or transfusion of at least two units of packed red blood cells) were statistically lower with rivaroxaban compared with fondaparinux (2.9 vs. 4.9%; P = 0.010). The mean length of hospital stay was significantly shorter in the rivaroxaban group (8.3 days, 95% CI 8.1-8.5 vs. 9.3 days, 9.1-9.5; P < 0.001).. Based on an indirect comparison of two consecutive cohorts, our data suggest that thromboprophylaxis with rivaroxaban is associated with less VTE and bleeding events than fondaparinux in unselected patients undergoing MOS. Prospective comparisons are warranted to confirm our findings.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Tests; Drug Administration Schedule; Female; Fondaparinux; Germany; Humans; Kaplan-Meier Estimate; Logistic Models; Longevity; Male; Middle Aged; Morpholines; Orthopedic Procedures; Polysaccharides; Postoperative Hemorrhage; Proportional Hazards Models; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Rivaroxaban; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism

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

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

Venous thromboembolism (VTE) is a common complication in hip fracture surgery (HFS). Fondaparinux (FPX) and enoxaparin (ENO) have been reported to decrease the incidence of VTE after HFS. The purpose of this study was to determine the efficacies of FPX and ENO and the superior agent for preventing VTE after HFS by performing a prospective study in a Japanese population.. Eighty-four Japanese patients who underwent HFS were assigned to either FPX (received FPX 1.5 or 2.5 mg/day for 14 days), ENO (received ENO 2000 IU once or twice/day for 14 days), or untreated control (CTRL) groups in order of surgery. All patients underwent ultrasonography of the lower extremities 7 days after HFS to evaluate the extent of deep-vein thrombosis. Incidence of VTE, D-dimer values measured at admission and 7 and 14 days after HFS, and the side effects of FPX and ENO were compared.. The incidence of VTE and the D-dimer values on days 7 and 14 in the FPX group were significantly lower than the corresponding levels in the CTRL group (P < 0.05). The D-dimer values on day 7 in the ENO group were significantly lower than those in the CTRL group, whereas the incidence of VTE was not significantly different. Side effects were observed in 3 cases: major bleeding occurred in 2 patients who received FPX, whereas minor bleeding occurred in 1 patient who received ENO.. We concluded that FPX was the superior agent for preventing VTE after HFS. However, patients receiving FPX should be monitored for bleeding.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Dose-Response Relationship, Drug; Enoxaparin; Factor X; Female; Fondaparinux; Humans; Incidence; Injections, Subcutaneous; Japan; Male; Polysaccharides; Postoperative Complications; Prospective Studies; Treatment Outcome; Venous Thromboembolism

Some patients with acute VTE who may previously have been exposed to heparin products have unrecognized antibodies implicated in heparin-induced thrombocytopenia (HIT). Antibody prevalence and patient consequences upon exposure to heparin, low-molecular-weight heparin, and fondaparinux are uncertain.. In this secondary analysis, we tested patients in the Matisse VTE studies at study entry for heparin-dependent antibodies and further tested patients with enzyme-linked immunosorbent assay (ELISA)-positive results for platelet-activating antibodies. We compared the risk of HIT (> 50% fall in platelet count, heparin-dependent antibodies, no contradicting features) between patients treated with heparin (either unfractionated or low molecular weight [enoxaparin]) vs those who received fondaparinux. Comparison groups for thrombocytopenia occurrence comprised patients with ELISA-positive, platelet-activating, antibody-positive results; ELISA-positive, but platelet-activating antibody-negative results; and randomly selected antibody-negative results.. A total of 127 of 3,994 patients (3.2%) had ELISA-positive results at baseline, but only 14 (0.4%; 95% CI, 0.2%-0.6%) had platelet-activating antibodies. Among these 14, four treated with unfractionated or low-molecular-weight heparin developed HIT compared with zero of 10 fondaparinux-treated patients (OR, 95; 95% CI, 8-1,123; P < .001). This frequency (four of four, 100%) significantly differed from that of both heparin-treated patients whose results were ELISA positive but platelet-activating antibody negative and from heparin-treated antibody-negative control subjects (zero of 15 and zero of 27, respectively; P < .001 for both).. Of patients with VTE, 0.4% had pathologic platelet-activating heparin-dependent antibodies rather than the 3.2% detected by the recommended cutoff of the commercial ELISA. Among study patients with acute VTE who had platelet-activating antibodies, treatment with fondaparinux reduced the risk of precipitating rapid-onset HIT.

Topics: Acute Disease; Antibodies; Anticoagulants; Enzyme-Linked Immunosorbent Assay; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Platelet Factor 4; Polysaccharides; Thrombocytopenia; Venous Thromboembolism

To describe and compare the conditions of use of fondaparinux and low molecular weight heparin (LMWH) in the prevention of venous thromboembolism in routine general practice with a focus on platelet monitoring.. This was an observational and pharmaco-epidemiological survey, performed in France in general practice in adult patients receiving thromboprophylaxis with fondaparinux or a LMWH. The study collected data on medical conditions justifying thromboprophylaxis, reasons for platelet monitoring and type of prescription.. Four hundred and seventy general practioners included 837 analysable patients (450 treated with fondaparinux and 387 with LMWH). In the fondaparinux group, the mean age was 61.5±17.3 and 259 (57.6 %) patients were women. In the LMWH group, the mean age was 61.7±17.8 and 205 (53.0 %) patients were women. The reasons of prescribing were: bedridden related to a severe acute medical illness in 255 (56.7 %) patients with fondaparinux and 244 (63.1 %) with LMWH, and reduction of mobility associated with trauma without fracture respectively in 121 (26.9 %) and 85 (22.0 %) of patients. Associated risk factors were varicose veins, obesity and a history of thrombosis. Platelet monitoring was prescribed in 168 (37.6 %) patients treated with fondaparinux. In this group, these prescription were considered "appropriate" in 94 (20.9 %) patients, of whom 76 (16.9 %) were monitored for screening purposes, and "not appropriate" in 67 (14.9 %) patients, because prescribed to monitor thrombo-prophylaxis. In the LMWH group, a platelet count was prescribed in 370 (96.1 %) patients, of whom 312 (81.0 %) receiving a prescription only in order to monitor thromboprophylaxis.. The results provided in the Ariane study were coherent with literature data (Etape and Depart studies). In comparison with the CNAM study, which evaluated prescription practices for LMWH in thromboprophylaxis in France in 1999, and which reported a global rate of platelet monitoring of 70.0 %, the rate reported in the Ariane study (81.0 %) seems to represent an improvement in the practice standards. Since 2009, Afssaps does not recommend a systematic monitoring with LMWH at acute or prophylactic dose, outside a post surgical context or in case of pre-treatment with unfractionated heparin.. The Ariane study provides important information on platelet monitoring in patients treated with fondaparinux or LMWH, and also on thromboprohylaxis in general practice.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Female; Follow-Up Studies; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Platelet Count; Polysaccharides; Practice Patterns, Physicians'; Risk Factors; Venous Thromboembolism

Fondaparinux has a favourable efficacy-safety profile but if major bleeding occurs, reversal of antithrombotic treatment is challenging. We present clinical and biological observations from patients treated with rFVIIa for bleeding under fondaparinux.. Fondaparinux-treated patients with bleeding (>10% haematocrit decrease) and cardiovascular collapse were eligible. Patients received a single 90 μg/kg bolus rFVIIa. Clinical success was defined as clinical bleeding control without thrombotic complication. A biological criterion of successful antagonization was defined as a >100% increase in peak thrombin generation (C(max)).. 8 patients were treated (5 ACS, 3 VTE). Patients received aspirin and clopidogrel (n = 5), eptifibatide (n = 2), fluindione (n = 5). In addition to standard haemostatic methods, all patients received rFVIIa and transfusion. Clinical progression was favourable in 4, with bleeding clinically controlled in <6 h. 1 patient died. Biological success was observed in 4 patients with lowest baseline anti-Xa (0.67-0.92 U/L); ¾ had clinical success. In patients with baseline anti-Xa >1.0 U/L (1.14-1.62 U/L), increase in C(max) was low; ¾ had no clinical bleeding control.. This series is the largest describing rFVIIa use to control bleeding in patients under fondaparinux. rVFIIa was considered efficient in 50%, suggesting inefficacy in the context of elevated anti-Xa.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Blood Transfusion; Factor VIIa; Female; Fondaparinux; Hemorrhage; Humans; Male; Middle Aged; Polysaccharides; Prospective Studies; Recombinant Proteins; Treatment Outcome; Venous Thromboembolism

The number of spinal fusion operations in the USA is rapidly rising, but little is known about optimal venous thromboembolism prophylaxis after spinal surgery.. To examine the use of and outcomes associated with venous thromboembolism prophylaxis after spinal fusion surgery in a cohort of 244 US hospitals..  We identified all patients with a principal procedure code for spinal fusion surgery in hospitals participating in the Premier Perspective database from 2003 to 2005, and searched for receipt of pharmacologic prophylaxis (subcutaneous unfractionated heparin, low molecular weight heparin, or fondaparinux) and/or mechanical prophylaxis (compression devices and elastic stockings) within the first 7 days after surgery. We also searched for discharge diagnosis codes for venous thromboembolism and postoperative hemorrhage during the index hospitalization and within 30 days after surgery.. Among 80,183 spinal fusions performed during the time period, cervical fusions were the most common (49.0%), followed by lumbar fusions (47.8%). Thromboembolism prophylaxis was administered to 60.6% of patients within the first week postoperatively, with the most frequent form being mechanical prophylaxis alone (47.6%). Of the 244 hospitals, 26.2% provided prophylaxis to ≥ 90% of their patients undergoing spinal fusion; however, 33.2% provided prophylaxis to fewer than 50% of their patients. The rate of diagnosed venous thromboembolism within 30 days after surgery was 0.45%, and the rate of postoperative hemorrhage was 1.1%..  Substantial variation exists in the use of thromboembolism prophylaxis after spinal fusion surgery in the USA. Nevertheless, overall rates of diagnosed thromboembolism after spinal fusion appear to be low.

Topics: Adult; Aged; Chemoprevention; Cohort Studies; Databases, Factual; Female; Fondaparinux; Hemorrhage; Heparin; Humans; Male; Middle Aged; Polysaccharides; Postoperative Complications; Retrospective Studies; Spinal Fusion; Stockings, Compression; Treatment Outcome; Venous Thromboembolism

Anti-factor Xa values in morbidly obese patients receiving standard doses of fondaparinux sodium for the prevention of venous thromboembolism (VTE) were analyzed in a retrospective chart evaluation.. The administration of low-molecular-weight heparins to obese patients (body mass index [BMI] of ≥30 kg/m(2)) at the dose recommended for VTE prophylaxis has been reported to result in increased thromboembolic events and decreased anti-factor Xa levels, and some evidence indicates that weight-based dosing adjustments may be appropriate. To study this phenomenon among morbidly obese patients (BMI of ≥40 kg/m(2)), a review of the charts of 45 adult patients for whom steady-state anti-factor Xa laboratory values were obtained after at least four fondaparinux injections was conducted; in all instances, fondaparinux sodium was given at the standard dose (2.5 mg once daily). Of the total of 47 anti-factor Xa values analyzed, 22 (47%) were below the study institution's target peak range (0.3-0.5 mg/L), 20 values (43%) were within the range, and 5 (11%) were above the range. No documented thromboembolic events occurred during hospitalization in the cases evaluated. A stepwise linear regression analysis of selected demographic and clinical variables indicated that better renal function, male sex, increased BMI, and fewer fondaparinux doses were associated with a greater likelihood of diminished anti-factor Xa activity in the cases evaluated.. Anti-factor Xa concentrations in morbidly obese patients receiving fondaparinux sodium 2.5 mg subcutaneously daily for VTE prophylaxis were within or above the target range in 53% of the instances evaluated.

Topics: Adult; Aged; Anticoagulants; Cross-Sectional Studies; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Linear Models; Male; Middle Aged; Obesity, Morbid; Polysaccharides; Retrospective Studies; Risk Factors; Venous Thromboembolism; Young Adult

Enoxaparin 40 mg/day (E) or fondaparinux 2.5 mg/day (F) are recommended to prevent venous thromboembolism (VTE) in medical and surgical patients at risk. Over the two years after switching from E to F in our 35-bed department of pulmonology and thoracic surgery, an increase in the number of transfusions was observed. A retrospective explanatory investigation was undertaken. Hospitalised patients in the two years before and after switching from E to F were compared. The files of all transfused patients were reviewed. A blinded independent committee adjudicated major bleeding events. In the investigated time period, the overall transfusion rate increased from 1.8% of 2,989 patients to 3.1% of 3,085 patients (p=0.002). Mean ages (58.4 vs. 59.1 years), proportions of surgical patients (63.6% vs. 58.4%), cancer patients (72.1% vs. 69.5%), and treated patients (≥ 1 dose of E or F: 51.8% vs. 52.5%) were similar. The number of medical patients transfused while receiving E or F did not increase significantly (0.9% vs. 1.3%, RR=1.45 [0.66-3.17], p=0.35). The number of surgical patients transfused postoperatively while receiving E or F increased significantly (0.7% vs. 1.9% of all surgical patients, relative risk [RR]=2.75 [1.45-5.23], p=0.001), including a significant increase in transfusions for major bleeding (0.2% vs. 0.9%, RR=5.97 [1.74-20.4], p<0.001). A multivariate analysis did not find confounding factors. The incidence of symptomatic postoperative pulmonary embolism remained very low (0.05% vs. 0.17%). In conclusion, in thoracic surgery patients, switching from enoxaparin to fondaparinux to prevent VTE was associated with a significant increase in the risk of postoperative major bleeding. A causal relationship appears plausible.

Topics: Anticoagulants; Antithrombins; Blood Transfusion; Drug Substitution; Enoxaparin; Female; Fondaparinux; France; Humans; Male; Middle Aged; Polysaccharides; Postoperative Hemorrhage; Retrospective Studies; Thoracic Surgical Procedures; Treatment Outcome; Venous Thromboembolism

The factor Xa inhibitor, fondaparinux was used for prevention of venous thromboembolism in the clinical setting. We evaluated the antithrombotic effect, complications and economic aspects of this agent in the patients undergoing laparoscopic surgery.. Forty one patients scheduled for laparoscopic abdominal surgery were divided into two groups. In group F (N = 33), patients received once-daily subcutaneous injection of fondaparinux (2.5 mg x day(-1)) for 4 postoperative days. In group E (N = 8), patients did not receive therapy. In group F, general anesthesia with transversus abdominis plane (TAP) block was administered during surgery, and general anesthesia with epidural anesthesia was performed in group E. We evaluated incidence of DVT (deep vein thrombosis), abnormal bleeding, other postoperative complications, and economic benefit to the hospital.. In both groups, no patient developed DVT Abnormal bleeding was observed in 7 patients of group E. Postoperative complications and pain were not different between the two groups. The revenue in group F was 34,434 yen/patient lower than that of group E due to Japanease insulance system.. No patients developed DVT and severe complications of fondaparinux after laparoscopic abdominal cancer surgery. However, revenue to the hospital decreased 34,434 yen/patient by use of analgestic method. We must consider cost-benefit in use of fondaparinux.

Topics: Aged; Aged, 80 and over; Anesthesia, General; Anticoagulants; Colonic Neoplasms; Cost-Benefit Analysis; Economics, Hospital; Factor Xa Inhibitors; Female; Fondaparinux; Health Care Costs; Humans; Laparoscopy; Male; Middle Aged; Polysaccharides; Postoperative Complications; Venous Thromboembolism

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

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

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 objectives of this study were to compare the risk of venous thromboembolism (VTE), bleeding, surgical site infection, and mortality in patients receiving aspirin or guideline-approved VTE prophylactic therapies (warfarin, low-molecular-weight heparins, synthetic pentasaccharides) in total knee arthroplasty (TKA). We analyzed clinical and administrative data from 93,840 patients who underwent primary TKA at 307 US hospitals over a 24-month period. Fifty-one thousand nine hundred twenty-three (55%) patients received warfarin, 37,198 (40%) received injectable agents, and 4719 (5%) received aspirin. After adjustment for patient and hospital factors, patients who received aspirin VTE prophylaxis (VTEP) had lower odds for thromboembolism compared to warfarin patients but with similar odds compared with injectable VTEP; there were no differences in risk of bleeding, infection, or mortality after adjustment. Our results suggest that aspirin, when used in conjunction with other clinical care protocols, may be effective VTEP for certain TKA patients.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Aspirin; Cohort Studies; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Polysaccharides; Postoperative Complications; Prevalence; Retrospective Studies; Risk Factors; Treatment Outcome; Venous Thromboembolism; Warfarin

Enoxaparin is the most frequently used low-molecular weight heparin in the world, given in order to prevent venous thromboembolism (VTE) in patients undergoing major orthopaedic surgery (MOS). Fondaparinux is an effective and safe alternative. The aim of our study was to compare the cost-effectiveness of enoxaparin and fondaparinux in the extended thromboprophylaxis of patients undergoing MOS in Italy. A decision-tree model was developed: probabilities of symptomatic events were derived from the published trials; use of resources in Italy was evaluated by means of a questionnaire administered to a panel of experts. Only the direct costs of VTE (acute treatment of events and of complications) were considered. Cost units were derived from the current cost of drugs, and from the Italian National Healthcare tariffs in 2007. Incremental cost-effectiveness ratios were analysed at three time points: 30 days, 1 year and 5 years. The higher cost of fondaparinux was counterbalanced by reduced rates of early DVT, early PE and prophylaxis-related major bleeding. If compared with enoxaparin, after 30 days of extended prophylaxis, fondaparinux is associated with a savings of 48.83 per patient; at the end of the first year, the savings increased to 72.13, and after 5 years, the savings are 74.36. One-way sensitivity analysis shows that the results are robust to the variation in unit costs for VTE-related care, or in event rates for both treatments. In conclusion, our model shows that, when administered for extended prophylaxis of VTE following MOS, fondaparinux is more effective and cost saving than enoxaparin.

Topics: Chemoprevention; Cost-Benefit Analysis; Drug Administration Schedule; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Humans; Italy; Models, Biological; Models, Economic; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Venous Thromboembolism

Topics: Anticoagulants; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Preoperative Care; Venous Thromboembolism

ENDORSE (Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting) study in 2006, was a multinational cross-sectional survey designed to assess the prevalence of venous thromboembolism (VTE) risk in the acute hospital care setting, and to determine the proportion of at-risk patients who receive appropriate prophylaxis. From the 358 randomly selected hospitals across 32 countries in the global registry, 9 Hungarian centers were included. According to the Hungarian results, the use of appropriate prophylaxis was more common in surgical patients but much less common in medical patients comparing to the worldwide average. ENDORSE 2-HUNGARY was a local survey to compare the prophylactic habits after two years and two months time period. In both surveys, the 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines were used to assess venous thromboembolism risk and to determine whether patients were receiving recommended prophylaxis. The one day survey ENDORSE 2-HUNGARY was repeated beside seven already audited hospitals, and in two newly recruited hospitals. A total of 886 patients were assessed for thrombosis risk on the basis of hospital chart review. Of these patients 59.0% (N=523) were judged at risk for VTE, including 100% (N=327) surgical and 35.1% (N=196) medical patients. 67.9% (N=355) of the total at-risk patients received ACCP-recommended VTE prophylaxis. Among surgical patients, 84.4% (N=276) received recommended prophylaxis compared with 40.3% (N=79) of medical patients. Results of the ENDORSE in 2006 and 2009 were compared, as well. The rate of appropriate prophylaxis use in at-risk patients did not changed significantly in surgical patients, however, a significant, 43.9% increase was found in medical patients (p=0.002), that proves the success of lectures presenting the facts and focusing to increase medical prophylaxis during the time period between the two studies. 59.7% of at-risk medical patients and 15.6% of surgical patients were unprotected against thrombosis in 2009. We should further increase the rate of at-risk patients receiving appropriate prophylaxis. We should reinforce the rationale for the increase of awareness of VTE risk in hospitalized medical patients, and to enhance the prophylaxis practice among healthcare professionals.

Topics: Adult; Aged; Anticoagulants; Cross-Sectional Studies; Female; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Hospitals; Humans; Hungary; Inpatients; International Cooperation; Male; Middle Aged; Polysaccharides; Prevalence; Risk Assessment; Risk Factors; Stockings, Compression; Venous Thromboembolism; Vitamin K

To illustrate clinical and management issues in the prevention of venous thromboembolism (VTE) in health systems.. Lack of evidence to guide the choice among available anticoagulants and the dosing, timing of initiation, and duration of therapy for VTE prevention in certain clinical situations can present challenges for clinicians. Patient characteristics such as the presence of obesity, epidural catheters, renal impairment, or heparin- induced thrombocytopenia complicate the decision-making process. The introduction of new anticoagulants may overcome some of the clinical challenges associated with VTE prophylaxis, but determining whether to add new agents to the formulary and restrict their use may pose management challenges. The safety, effectiveness, ease of use, and cost of new agents compared with older agents already on the formulary are primary considerations.. An understanding of the clinical and management issues involved in preventing VTE is needed to improve the use of anticoagulants and reduce the incidence of VTE in health systems.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Bariatric Surgery; Colonic Neoplasms; Dalteparin; Female; Fondaparinux; Heart Failure; Humans; Kidney Diseases; Male; Middle Aged; Obesity; Perioperative Care; Pharmacy Service, Hospital; Polysaccharides; Venous Thromboembolism

Fondaparinux is a synthetic antithrombotic agent with specific anti-factor Xa activity. A population pharmacokinetic model of fondaparinux, based on data obtained in patients included in phase II/III trials, has been described. However, the validity of this model in everyday practice needed to be confirmed. This study was a multicenter, prospective cohort study in consecutive orthopaedic patients treated with 2.5 mg of fondaparinux. Anti-Xa activities were recorded in 809 patients. Population parameters and inter-individual variability were estimated using NONMEM VI software. A two-compartment model with first-order absorption best described fondaparinux pharmacokinetics. Covariates partly explaining inter-individual variability were body weight, age and creatinine clearance estimated by the simplified Modification of Diet in Renal Disease formula (MDRD). A body weight less than 50 kg and moderate renal failure increased drug exposure. Although the population pharmacokinetic model of fondaparinux was described, this one requires to be validated in everyday practice.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Body Weight; Computer Simulation; Creatinine; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Fondaparinux; France; Hemorrhage; Humans; Kidney; Male; Middle Aged; Models, Biological; Nonlinear Dynamics; Orthopedic Procedures; Polysaccharides; Prospective Studies; Reproducibility of Results; Treatment Outcome; Venous Thromboembolism; Young Adult

Topics: Anticoagulants; Antithrombins; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Clinical Trials as Topic; Cost-Benefit Analysis; Dabigatran; Enoxaparin; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Models, Economic; Morpholines; Polysaccharides; Postoperative Complications; Pyridines; Quality-Adjusted Life Years; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

This guideline focuses on the primary prevention of venous thromboembolism (VTE) in Korea. The guidelines should be individualized and aim at patients scheduled for major surgery, as well as patients with a history of trauma, high-risk pregnancy, cancer, or other severe medical illnesses. Currently, no nation-wide data on the incidence of VTE exist, and randomized controlled trials aiming at the prevention of VTE in Korea have yielded few results. Therefore, these guidelines were based on the second edition of the Japanese Guidelines for the Prevention of VTE and the eighth edition of the American College of Chest Physicians (ACCP) Evidenced-Based Clinical Practice Guidelines. These guidelines establish low-, moderate-, and high-risk groups, and recommend appropriate thromboprophylaxis for each group.

Topics: Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Republic of Korea; Risk Factors; Venous Thromboembolism; Warfarin

Many acutely ill medical patients are at significant risk for developing venous thromboembolism (VTE) during hospitalization. Venous thromboembolism risk arises from both the presenting clinical condition as well as predisposing risk factors, such as advanced age. Thromboprophylaxis is underprescribed in these patients. Thrombotic risk assessment could encourage the prescribing of thromboprophylaxis and, therefore, improve patient protection against VTE. Current guidelines from the American College of Chest Physicians and the International Union of Angiology (IUA) recommend thromboprophylaxis with low-dose unfractionated heparin (UFH), a low-molecular-weight heparin (LMWH), or fondaparinux for acutely ill medical patients with VTE risk factors. However, the optimal dose regimen for UFH is unclear. The 2006 evidence-based guidelines from the IUA recommend a 3-times-daily dose regimen for UFH. However, UFH is usually administered twice daily despite a lack of evidence for the superiority of this regimen. Both heparin-induced thrombocytopenia and bleeding are associated with UFH, and to a lesser degree with alternative anticoagulants, such as the LMWHs. If utilized, an appropriate prophylaxis regimen in medical patients can reduce the risk of VTE and its burden.

Topics: Anticoagulants; Causality; Drug Administration Schedule; Drug Prescriptions; Drug Utilization; Evidence-Based Medicine; Fondaparinux; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Incidence; Patient Selection; Polysaccharides; Practice Guidelines as Topic; Practice Patterns, Physicians'; Risk Assessment; Time Factors; Venous Thromboembolism

Topics: Adult; Analgesia, Epidural; Anticoagulants; Cesarean Section; Female; Fondaparinux; Guidelines as Topic; Humans; Polysaccharides; Pregnancy; Pregnancy Complications, Cardiovascular; Time Factors; Venous Thromboembolism

Patients undergoing general surgical procedures are at increased risk for venous thromboembolism (VTE). Compliance rates with established guidelines for VTE thromboprophylaxis in patients at moderate-to-high risk are notably low. Recent literature has demonstrated that fondaparinux is associated with lower costs and fewer VTEs than enoxaparin in patients undergoing major orthopedic surgery (MOS), but data are limited in patients undergoing general surgery. This study was conducted to evaluate the cost implications and relative real-world effectiveness of fondaparinux vs. enoxaparin in general surgery patients.. Data were obtained from inpatient billing records from over 500 hospitals using Premier's Perspective Comparative Database. Patients hospitalized for general surgery between July 1, 2003 and January 31, 2006 were eligible for inclusion. Eligible patients were included if they received fondaparinux or enoxaparin after their general surgery date. Patients were excluded if they received both anticoagulants on their first day of therapy, were <18 years of age on the surgery date, or did not have data 6 months prior and 1 month post hospitalization. Included patients were stratified into two cohorts based on their first anticoagulant, fondaparinux or enoxaparin. Patients were matched in each group on 1:1 case-control matching based on propensity scores.. A total of 5364 patients were included (n = 2682 for each cohort) from 326 unique hospitals. Average total costs per patient for the fondaparinux group were significantly lower than the enoxaparin group ($15 156 vs. 17 741, p < 0.0001). Patients receiving fondaparinux were significantly less likely to experience a VTE (2.80 vs. 3.77%, p = 0.046, a 35% relative risk reduction). No significant differences in bleeding events between the cohorts were observed (p = 0.6047), and no significant differences in all-cause inpatient death were noted (p = 0.3673).. Fondaparinux was associated with significantly lower costs and fewer VTEs compared to enoxaparin without an increase in bleed rates or all-cause inpatient mortality. The findings from this study are limited by the retrospective study design and should only be generalized to a similar patient population.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Cohort Studies; Enoxaparin; Female; Fondaparinux; Humans; Incidence; Male; Middle Aged; Polysaccharides; Postoperative Complications; Surgical Procedures, Operative; Venous Thromboembolism; Young Adult

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

Fondaparinux is a synthetic pentasaccharide belonging to a new group of anticoagulants that inhibit thrombin formation by inhibiting Factor Xa, which is located at the crossing of both the intrinsic and extrinsic pathways. It has a favorable pharmacokinetic profile, and its effect is predictable and the drug does not need platelet monitoring. Current evidence suggest that fondaparinux is as effective as, if not more than, enoxaparin in the prevention of venous thromboembolism in the postoperative period. It has also been found to have similar effectiveness to enoxaparin and unfractionated heparin in the treatment of venous and pulmonary embolism, respectively. In the field of cardiology, studies have demonstrated that in the setting of acute coronary syndromes, treatment with fondaparinux is not inferior to enoxaparin in preventing major cardiac outcomes, but it is associated with lower risk of bleeding complications, irrespective of the use of percutaneous coronary intervention. During percutaneous coronary intervention, there is a slightly increased risk of catheter thrombosis, which is removed when used along with unfractionated heparin. However, in patients with ST-elevation myocardial infarction, the benefit has been shown in those either receiving thrombolysis or not undergoing any revascularization, but not in subjects undergoing primary percutaneous coronary intervention where unfractionated heparin is still preferred.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Interactions; Enoxaparin; Factor Xa Inhibitors; Fondaparinux; Humans; Polysaccharides; Venous Thromboembolism

The oral anticoagulant warfarin is a common medication that requires special consideration in the perioperative period. Although some procedures do not require warfarin interruption, the majority will necessitate its temporary cessation due to the risk of bleeding. Determining whether patients will benefit from the temporary use of a heparin product while warfarin is discontinued perioperatively (so-called "bridging" therapy) needs to take into consideration the risk of bleeding balanced with the risk of thromboembolism. Perioperative care also requires minimizing the risk of venous thromboembolism (VTE). Understanding the patient-specific and procedure-specific risks for VTE is paramount to employ optimal risk reduction strategies. This article uses a case-based approach to present the topics of perioperative warfarin management and postoperative VTE prevention.

Topics: Adult; Aged; Anticoagulants; Aspirin; Drug Administration Schedule; Drug Synergism; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Perioperative Care; Polysaccharides; Risk Factors; Vena Cava Filters; Venous Thromboembolism; Warfarin

Guidelines concerning the prevention and treatment of pregnancy-associated venous thromboembolism (VTE) have been elaborated by the American College of Chest Physicians and published in Chest in 2008. In this review, they have been compared with European guidelines and discussed taking into account the papers published since 2008.Most recommendations are of low grade of evidence because randomized studies are lacking during pregnancy and many reflect guidelines proposed by experts. The decisions on the most appropriate prophylaxis, dose to be administered and moment of pregnancy for starting prophylaxis are often decided case by case after careful assessment of the risk of pregnancy-associated VTE, on one hand, and the risk for the mother, on the other.Risk factors (age >or= 35, obesity, history of VTE with or without sequellae, in vitro fertilization)or thrombophilia have to be taken into account. Scores have been proposed to improve standardisation and evaluation of the risk of VTE and they should be validated.

Topics: Abnormalities, Drug-Induced; Adult; Anticoagulants; Benzimidazoles; Blood Loss, Surgical; Cesarean Section; Contraindications; Dabigatran; Europe; Evidence-Based Medicine; Female; Fetus; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Morpholines; Polysaccharides; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders; Pyridines; Rivaroxaban; Societies, Medical; Thiophenes; Thrombophilia; United States; Uterine Hemorrhage; Venous Thromboembolism; Warfarin

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

While venous thromboembolism (VTE) is a well recognised occurrence in clinical practice in the developed world, with event rates of at least 2-3 million per year, little attention is paid to this entity in the developing world where the burden of infectious diseases and limited access to care have not recognised VTE as a significant cause of morbidity and mortality. The opportunity for Africa to do better as the inevitable recognition of the consequence of VTE becomes more apparent is available using basic tools and therapies.

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

This article about hemorrhagic complications of anticoagulant and thrombolytic treatment is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Bleeding is the major complication of anticoagulant and fibrinolytic therapy. The criteria for defining the severity of bleeding vary considerably between studies, accounting in part for the variation in the rates of bleeding reported. The major determinants of vitamin K antagonist (VKA)-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that VKA therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0-3.0), is associated with a lower risk of bleeding than therapy targeted at an INR > 3.0. The risk of bleeding associated with IV unfractionated heparin (UFH) in patients with acute venous thromboembolism is < 3% in recent trials. This bleeding risk may increase with increasing heparin dosages and age (> 70 years). Low-molecular-weight heparin (LMWH) is associated with less major bleeding compared with UFH in acute venous thromboembolism. Higher doses of UFH and LMWH are associated with important increases in major bleeding in ischemic stroke. In ST-segment elevation myocardial infarction, addition of LMWH, hirudin, or its derivatives to thrombolytic therapy is associated with a small increase in the risk of major bleeding, whereas treatment with fondaparinux or UFH is associated with a lower risk of bleeding. Thrombolytic therapy increases the risk of major bleeding 1.5-fold to threefold in patients with acute venous thromboembolism, ischemic stroke, or ST-elevation myocardial infarction.

Topics: Anticoagulants; Brain Ischemia; Evidence-Based Medicine; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Hirudins; Humans; International Normalized Ratio; Myocardial Infarction; Polysaccharides; Risk Factors; Severity of Illness Index; Thrombolytic Therapy; Treatment Outcome; Venous Thromboembolism; Vitamin K

This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithrombotic and Thrombolytic Therapy: 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 suggestions imply that individual patient values may lead to different choices (for a full discussion of the grading, see the "Grades of Recommendation" chapter by Guyatt et al). Among the key recommendations in this chapter are the following: we recommend that every hospital develop a formal strategy that addresses the prevention of VTE (Grade 1A). We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A), and we recommend that mechanical methods of thromboprophylaxis be used primarily for patients at high bleeding risk (Grade 1A) or possibly as an adjunct to anticoagulant thromboprophylaxis (Grade 2A). For patients undergoing major general surgery, we recommend thromboprophylaxis with a low-molecular-weight heparin (LMWH), low-dose unfractionated heparin (LDUH), or fondaparinux (each Grade 1A). We recommend routine thromboprophylaxis for all patients undergoing major gynecologic surgery or major, open urologic procedures (Grade 1A for both groups), with LMWH, LDUH, fondaparinux, or intermittent pneumatic compression (IPC). For patients undergoing elective hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or a vitamin K antagonist (VKA); international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0 (each Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1B), a VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 1B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty or HFS receive thromboprophylaxis for a minimum of 10 days (Grade 1A); for hip arthroplasty and HFS, we recommend continuing thromboprophylaxis > 10 days and up to 35 days (Grade 1A). We recommend that all major trauma and all spinal cord injury (SCI) patients receive thromboprophylaxis (Grade 1A). In patients admitted to hospital with an acute medical illness, we recommend thromboprophylaxis with LMWH, LDUH, or fondaparinux (each Grade 1A). We recommend that, on admission to the ICU, all patients be assessed for their risk of VTE, and th

Topics: Anticoagulants; Drug Therapy, Combination; Evidence-Based Medicine; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Polysaccharides; Postoperative Complications; Risk Assessment; Venous Thromboembolism; Vitamin K

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Aspirin; Enoxaparin; Fondaparinux; Humans; Orthopedics; Platelet Aggregation Inhibitors; Polysaccharides; Risk Factors; Venous Thromboembolism

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Aspirin; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Risk Assessment; Risk Reduction Behavior; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Austria; Drug Administration Schedule; Fondaparinux; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Injections; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Venous Thromboembolism

The hospitalized medical patient in the US today has multiple risk factors for venous thromboembolism (VTE) and is therefore at a significant risk of developing this condition both during hospitalization and after discharge. The American College of Chest Physicians (ACCP) guidelines recommend pharmacologic prophylaxis unless there are contraindications. Low-molecular-weight heparins (LMWH) are the preferred class of drugs due to multiple advantages, including daily dosing and a decreased risk of heparin-induced thrombocytopenia, to name a few. Several emerging oral anticoagulants, including Factor Xa inhibitors and direct thrombin inhibitors, are currently being evaluated in Phase III clinical trials as prophylaxis against VTE in medically ill patients and may some day replace parenteral drugs.

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

Clinical trials have shown differences in efficacy among anticoagulants used for venous thromboembolism (VTE) prophylaxis after hip fracture surgery, but the applicability of their results is limited by constraints of the clinical trial setting. We conducted this retrospective cohort study to assess VTE after hip fracture surgery in patients who received prophylaxis with dalteparin, enoxaparin, fondaparinux, or unfractionated heparin in a hospital setting. After adjustments were made for demographic differences, risk for VTE was significantly higher for dalteparin (odds ratio [OR], 1.4; 95% confidence interval [CI], 0.99-1.92), enoxaparin (OR, 1.4; 95% CI, 1.05-1.86), and unfractionated heparin (OR, 1.9; 95% CI, 1.39-2.58) compared with fondaparinux. These findings confirm the results of clinical trials in a real-world setting.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anticoagulants; Cohort Studies; Dalteparin; Enoxaparin; Female; Follow-Up Studies; Fondaparinux; Fracture Fixation, Intramedullary; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Incidence; Logistic Models; Male; Odds Ratio; Polysaccharides; Postoperative Complications; Premedication; Probability; Radiography; Retrospective Studies; Risk Assessment; Treatment Failure; Treatment Outcome; Venous Thromboembolism

Many factors impact the choice of anticoagulant used for venous thromboembolism prophylaxis following orthopaedic surgery. Thrombocytopenia (TCP) is an important factor from both clinical and economic perspectives, warranting assessment between the available agents. Thus, a retrospective cohort analysis was conducted to: (1) report the occurrence of TCP in a treatment and no treatment group, (2) evaluate the impact of anticoagulant choice on TCP within the treatment group, and (3) assess the clinical and economic implications of TCP in the treatment group.. Administrative claims from a hospital database were used to identify patients with hip replacement, knee replacement, or hip fracture surgery. The treatment group (n = 144,806) included patients receiving one of the following injectable anticoagulants post-operatively: dalteparin (n = 16,109); enoxaparin (n = 97,827); fondaparinux (n = 12,532); or unfractionated heparin (UFH) (n = 18,338). The no treatment group consisted of patients who did not receive one of the four injectable anticoagulants (n = 112,574) post-operatively. Outcomes were assessed for the hospitalization period plus 2 months post-discharge while controlling for relevant demographic and clinical characteristics.. The occurrence of TCP was 1.0% in the no treatment group and 1.7% in the treatment group. Within the treatment group, patients who received dalteparin, enoxaparin, and UFH were significantly more likely to experience coded thrombocytopenia than those in the no treatment group. The risk of TCP among patients who received fondaparinux was not significantly different from the no treatment cohort (odds ratio [OR] = 1.15, 95% CI: 0.96-1.37, P = 0.13). Patients in the treatment group with coded TCP had 22% higher adjusted mean total healthcare costs (relative cost difference) compared to those without ($19,134 vs. $15,400, respectively, P < 0.0001), greater mean length of stay (LOS) (8.4 vs. 5.7, respectively), and a greater likelihood of experiencing a venous thromboembolic (VTE) event (6.1% vs. 2.4%, respectively).. Patients treated with fondaparinux did not have a significant increase in the risk of TCP compared to patients not on prophylaxis. In contrast, the risk was increased in those treated with enoxaparin, dalteparin, and UFH compared to the patients not on prophylaxis. Patients in the treatment group with coded TCP experienced more thrombotic events, incurred greater per patient healthcare costs, and experienced longer LOS than patients without coded TCP. Therefore, the risk of TCP should be considered when evaluating the profile of injectable anticoagulants since TCP may have important clinical and economic implications.

Topics: Aged; Anticoagulants; Cohort Studies; Dalteparin; Enoxaparin; Female; Fondaparinux; Health Care Costs; Heparin; Humans; Incidence; Injections; Length of Stay; Male; Odds Ratio; Orthopedic Procedures; Polysaccharides; Retrospective Studies; Risk Assessment; Thrombocytopenia; Venous Thromboembolism

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

A model was developed to estimate costs and clinical effectiveness of fondaparinux compared with enoxaparin after hip fracture surgery in Sweden. Outcomes and costs of venous thromboembolism (VTE)-related care from a health care perspective were incorporated, with symptomatic deep-vein thrombosis and pulmonary embolism, recurrent VTE, post-thrombotic syndrome, major haemorrhage and all-cause death being included. Event probabilities were derived from fondaparinux clinical trial data and published data. VTE-related resource use and associated costs as well as costs of prophylaxis were based on local Swedish data. Extended prophylaxis with fondaparinux could avoid an additional 28 symptomatic VTE per 1,000 patients compared with extended prophylaxis with enoxaparin in hip fracture surgery patients. Although the prophylaxis costs were higher in the fondaparinux group, these were offset by the lower costs associated with treating fewer VTE, which thus indicates that extended fondaparinux prophylaxis is the dominant alternative when compared with enoxaparin in hip fracture surgery.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cost-Benefit Analysis; Fondaparinux; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Models, Econometric; Outcome Assessment, Health Care; Polysaccharides; Sweden; Treatment Outcome; Venous Thromboembolism

Venous thromboembolism (VTE) is an important cause of morbidity and mortality following major orthopedic surgeries. In clinical trials, fondaparinux and low molecular weight heparins have been shown to be more effective than unfractionated heparin (UFH) in preventing VTE. We retrospectively analyzed a large hospital discharge database to assess the occurrence of clinically detected VTE as a function of the injectable antithrombotic agent used for VTE prophylaxis in orthopedic surgery.. The Premier's Perspective database, representing over 500 hospitals across the US, was utilized to identify patients receiving dalteparin, enoxaparin, fondaparinux, or UFH following hip or knee replacement or hip fracture surgery between January 2003 and March 2005. The primary outcome was the proportion of patients in each cohort with a VTE, while secondary outcomes included VTE occurrence during index hospitalization, and proportion of patients with a VTE-associated hospital readmission.. A total of 144,806 patients were included in the study. Significantly fewer fondaparinux patients experienced a VTE event (1.5%) compared to enoxaparin (2.3%), dalteparin (2.1%), and UFH (4.2%). After controlling for baseline covariates, the odds of experiencing a VTE was significantly higher for other treatments when compared to fondaparinux (odds ratios: dalteparin=1.22 [95% CI: 1.01 to 1.46] p=0.0370; enoxaparin=1.39 [1.19 to 1.62], p<0.0001; UFH=1.98 [1.67 to 2.34], p<0.0001). Significantly fewer fondaparinux-treated patients experienced an event during the index hospitalization or were readmitted for a VTE compared to other treatments.. Similar to clinical trial findings, patients receiving fondaparinux in this study experienced fewer VTE events following orthopedic surgeries.

Topics: Aged; Chemoprevention; Cohort Studies; Dalteparin; Data Collection; Enoxaparin; Female; Fondaparinux; Heparin; Humans; Male; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Premedication; Retrospective Studies; Venous Thromboembolism

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 cost, effectiveness, and safety of injectable anticoagulants used for thromboprophylaxis after orthopedic surgery were compared.. This retrospective, observational, cross-sectional, cohort analysis of inpatient billing data was conducted from the institutional perspective. Patients who received dalteparin, enoxaparin, fondaparinux, or unfractionated heparin after orthopedic surgery were included in the analysis. The primary outcome measure was the mean aggregated cost per patient treated with each injectable anticoagulant. Secondary outcomes included the percentages of patients in each treatment group who had a venous thromboembolism (VTE) or major bleeding episode.. Mean total adjusted costs were significantly lower for fondaparinux ($18,019) compared with other anticoagulants, with unfractionated heparin being the most costly ($20,835). Relative adjusted cost differences were 1.4% (p = 0.0127), 1.8% ( p = 0.0105), and 14.6% (p < 0.0001) higher for enoxaparin, dalteparin, and unfractionated heparin, respectively, compared with fondaparinux. Significantly fewer fondaparinux-treated patients had a VTE event compared with the other treatment groups. The use of dalteparin was associated with fewer major bleeding events, and no significant differences in the rate of major bleeding events were observed among groups treated with fondaparinux, enoxaparin, or unfractionated heparin.. A retrospective analysis of inpatient billing data showed that, among orthopedic surgery patients, fondaparinux was associated with lower institutional cost and a lower frequency of VTE than were dalteparin, enoxaparin, and unfractionated heparin. Dalteparin was associated with a lower rate of major bleeding events than was fondaparinux, but there were no significant differences in such events among fondaparinux, enoxaparin, and unfractionated heparin.

Topics: Aged; Aged, 80 and over; Anticoagulants; Chemoprevention; Cost-Benefit Analysis; Dalteparin; Enoxaparin; Female; Fondaparinux; Heparin; Hospital Costs; Humans; Injections; Male; Middle Aged; Observation; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Postoperative Hemorrhage; Retrospective Studies; Venous Thromboembolism

Venous thromboembolism (VTE) is a common complication among hospitalized patients. Pharmacological thromboprophylaxis has emerged as the cornerstone for VTE prevention. As trials on thromboprophylaxis in medical patients have proven the efficacy of both low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH), all acutely medical ill patients should be considered for pharmacological thromboprophylaxis. Unlike in the surgical setting where the risk of associated VTE attributable to surgery is well recognized, and where widespread use of pharmacological thromboprophylaxis and early mobilization has resulted in significant reductions in the risk of VTE, appropriate VTE prophylaxis is under-used in medical patients. Many reasons for this under-use have been identified, including low perceived risk of VTE in medical patients, absence of optimal tools for risk assessment, heterogeneity of patients and their diseases, and fear of bleeding complications. A consistent group among hospitalized medical patients is composed of elderly patients with impaired renal function, a condition potentially associated with bleeding. How these patients should be managed is discussed in this review. Particular attention is devoted to LMWHs and fondaparinux and to measures to improve the safety and the efficacy of their use.

Topics: Aged; Anticoagulants; Drug Monitoring; Fondaparinux; Guideline Adherence; Heparin; Heparin, Low-Molecular-Weight; Humans; Polysaccharides; Practice Guidelines as Topic; Renal Insufficiency; Venous Thromboembolism