fondaparinux and Chronic-Disease

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

Chronic kidney disease (CKD) is prevalent and affects an ever-increasing proportion of patients presenting with acute coronary syndrome (ACS). Patients with CKD have a higher risk of ACS and significantly higher mortality, and are also predisposed to increased bleeding complications. Antiplatelet and antithrombotic drugs form the bedrock of management of patients with ACS. Most randomized trials of these drugs exclude patients with CKD, and current guidelines for management of these patients are largely based on these trials. We aim to review the safety and efficacy of these drugs in patients with CKD presenting with ACS.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Chronic Disease; Clinical Trials as Topic; Clopidogrel; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin; Hirudins; Humans; Kidney Diseases; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Polysaccharides; Prasugrel Hydrochloride; Recombinant Proteins; Thiophenes; Ticagrelor; Ticlopidine; Uremia

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

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

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

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

To study the effect of fondaparinux, a new antithrombotic agent, as an anticoagulant during a 4-hour conventional hemodialysis session. materials and methods: Fondaparinux was administered as an anticoagulant to 16 chronic hemodialysis patients during a single 4-hour hemodialysis session at an intravenous bolus dose of 2.5 mg. Eight patients were using high-flux polyester polymer alloy (PEPA) dialyzers (Group A) and the remainder low-flux polysulfone dialyzers (Group B), whilst all had received conventional doses of tinzaparin sodium as an anticoagulant during the previous month. The dialyzers were primed with 1 l of normal saline containing 5,000 IU of unfractionated heparin. Blood samples for the measurement of INR, APTT (activated partial thromboplastin time) and anti-Xa levels were taken before the study dialysis session (pre), 5 min postdialysis (post), and before the next dialysis session (next). Mean fibrin/clot formation in the extracorporeal circuit and dialyzer was assessed macroscopically by visual inspection and was graded using a 4-point scale.. Predialysis anti-Xa levels were 0.04 A+/- 0.03 IU/ml in Group A, and 0.025 A+/- 0.025 IU/ml in Group B (p = NS). Postdialysis anti-Xa levels were significantly higher than predialysis levels in both groups (Group A = 0.16 A+/- 0.04 IU/ml, Group B = 0.46 A+/- 0.12 IU/ml, p < 0.02 for both) and significantly higher in Group B compared to Group A (p < 0.025). Anti-Xa levels before the next dialysis session were 0.06 A+/- 0.04 IU/ml in Group A and 0.25 A+/- 0.06 IU/ml in Group B (p < 0.0001 between Groups A and B). APTT values were significantly higher in postdialysis than predialysis samples for both groups (higher by 27.0 A+/- 26.0% in Group A and 24.3 A+/- 31.9% in Group B). No significant differences were found when comparing APTT values in pre, post and next samples between Groups A and B. No differences were also found between pre, post and next samples for INR values, either within or between groups. Mean fibrin/ clot formation score in the extracorporeal circuit at the end of the study dialysis session was significantly higher in patients of Group A than those of Group B (p < 0.05). Dialysis had to be terminated before the completion of 4 hours in 2 patients of Group A because of the presence of extensive fibrin/clots in the circuit and dialyzer.. Our findings indicate that fondaparinux sodium at an intravenous dose of 2.5 mg can be used successfully as an anticoagulant during a 4-hour conventional hemodialysis session in patients dialyzed with low-flux polysulfone dialyzers, but not in those dialyzed with high-flux dialyzers. However, anti-Xa levels in the former patients were still increased before the next dialysis session, potentially exposing the patients to an increased risk of bleeding.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Chronic Disease; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Injections, Intravenous; International Normalized Ratio; Kidney Diseases; Male; Middle Aged; Partial Thromboplastin Time; Polysaccharides; Renal Dialysis