fondaparinux and Postoperative-Complications

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

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

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Clinical Trials as Topic; Coronary Thrombosis; Endothelium, Vascular; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hirudins; Humans; Myocardial Ischemia; Peptide Fragments; Platelet Activation; Polysaccharides; Postoperative Complications; Recombinant Proteins; Thrombin

Disseminated intravascular coagulation (DIC) is the physiologic result of pathologic overstimulation of the coagulation system. Despite multiple triggers, a myriad of laboratory abnormalities, and a clinical presentation ranging from gross hemostatic failure to life-threatening thrombosis, or even both simultaneously, a simplified clinical approach augmented by a few readily available tests allows prompt identification of the process and elucidation of treatment opportunities. Platelet counts in DIC may be low, especially in acute sepsis-associated DIC, yet increased in malignancy-associated chronic DIC. Thrombotic risk is not a function of the platelet count, and thrombocytopenia does not protect the patient from thrombosis. The stratification of both thrombotic risk and hemorrhagic risk will be addressed.

Topics: Adenocarcinoma; Aged; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Esophageal Neoplasms; Fatal Outcome; Fondaparinux; Foodborne Diseases; Hemorrhage; Heparin; Hepatitis C, Chronic; Humans; Male; Middle Aged; Multiple Organ Failure; Polysaccharides; Postoperative Complications; Thrombocytopenia; Thrombophlebitis; Thrombosis; Vibrio Infections; Vibrio vulnificus; Young Adult

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

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

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

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

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

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

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

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

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

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated syndrome associated with heparin exposure, a falling platelet count and a high risk of thrombosis. Cardiovascular patients are at increased risk of HIT due to wide use of heparin in this population. Should HIT be suspected, heparin must be avoided in most situations, and anticoagulation with an alternative anticoagulant should be instituted. Preferred agents include the direct thrombin inhibitors argatroban and lepirudin, whilst bivalirudin or desirudin (other direct thrombin inhibitors) can be used in some situations. The indirect thrombin inhibitors, danaparoid and fondaparinux, can also be considered at times. These agents and their use in cardiac patients, including patients with acute coronary syndrome, percutaneous coronary interventions, acute ST elevation myocardial infarction or cardiac surgery, will be reviewed.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Cardiovascular Diseases; Chondroitin Sulfates; Dermatan Sulfate; Drug Administration Schedule; Factor Xa Inhibitors; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia

To review the epidemiology and pathogenesis of venous thromboembolism (VTE) in surgical cancer patients, in addition to the use of thromboprophylaxis in major abdominal surgery, such as low-molecular-weight heparin (LMWH) and fondaparinux.. Systematic review of the literature, focussing on risk factors for VTE, parenteral methods of thromboprophylaxis, approaches to prolonged prophylaxis, and effects on patient survival.. Patients with cancer undergoing abdominal surgery are at substantially higher risk for VTE than patients without cancer. Furthermore, prolonged thromboprophylaxis for up to 4 weeks is more effective than short-term administration in these high-risk patients. The concurrent use of graduated compression stockings has a synergistic effect on the reduction in VTE risk.. Thromboprophylaxis with LMWH has been shown to minimise the incidence of thromboembolic events, and is a well-established therapy worldwide. The American College of Chest Physicians recommends the routine use of thromboprophylaxis, with LMWH or unfractionated heparin, in patients with cancer who are undergoing surgical procedures, and the appropriate use of these thromboprophylactic agents has significant implications for the clinical care and quality of life of surgical patients with cancer.

Topics: Abdomen; Anticoagulants; Bandages; Combined Modality Therapy; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Polysaccharides; Postoperative Complications; Thromboembolism

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A new generation of antithrombotic agents that target a single enzyme within the procoagulant cascade is making its way into mainstream clinical practice. Borrowing selectively from the properties of their parent anticoagulant, unfractionated heparin, as well as from those of peptide anticoagulants from reptile or insect venoms, designers of the new drugs have created targeted inhibitors of thrombin, factor Xa, or other specific factors in the procoagulant pathways. These new agents promise efficacy and safety profiles far more favorable than those of conventional anticoagulants for thromboprophylaxis after major orthopedic surgery and require no laboratory monitoring of drug efficacy in this setting. Ximelagatran, the oral "prodrug" of the direct thrombin inhibitor melagatran, is in phase III of clinical development. Clinical trials using various dosages of ximelagatran, sometimes preceded by subcutaneous melagatran, as thromboprophylaxis after total hip or knee replacement surgery have suggested efficacy equal to or better than that of warfarin and enoxaparin. The best dosing regimen and optimal timing of first dose for melagatran and ximelagatran remain to be determined, as do the mechanism and impact of drug disturbance of hepatic function. Fondaparinux, a selective, synthetic inhibitor of factor Xa, has been shown in large clinical trials to be superior to low-molecular-weight heparins and is approved as a fixed once-daily subcutaneous 2.5-mg dose for thromboprophylaxis for hip or knee replacement surgery and after hip fracture repair. Fixed-dose fondaparinux 2.5 mg initiated 6 to 8 hours after surgery achieved superior efficacy and comparable safety in head-to-head comparisons with enoxaparin for the prevention of venous thromboembolism after major orthopedic surgery. Fondaparinux is the only agent approved for use in hip fracture patients in the United States at this time and has recently gained approval for extended prophylaxis in this patient population.

Topics: Anticoagulants; Azetidines; Benzylamines; Clinical Trials as Topic; Factor Xa Inhibitors; Fondaparinux; Glycine; Heparin; Heparin, Low-Molecular-Weight; Humans; Models, Biological; Orthopedics; Polysaccharides; Postoperative Complications; Thromboembolism; Thrombolytic Therapy

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

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

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

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

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

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

Venous thromboembolism is a serious, frequent, and potentially fatal complication of major orthopedic surgery. Currently available pharmacologic agents for the prevention of venous thromboembolism in this high-risk population consist of the oral anticoagulants and the heparin family of antithrombotic agents (unfractionated heparin, low-molecular-weight heparin, heparinoids). These classes of agents interfere with the activity of both thrombin and factor Xa (or their respective zymogens) to varying degrees. Newer antithrombotic agents in various stages of development exert their antithrombotic effect through a more targeted mechanism of action. Direct factor Xa inhibitors and the newest class of antithrombotic agents, the indirect factor Xa inhibitors, the prototype of which is the synthetic pentasaccharide fondaparinux sodium, limit fibrin formation through their exclusive inactivation of factor Xa. Clinical data from venous thromboembolism prophylaxis trials in hip and knee replacement and hip fracture surgeries, including the recently completed fondaparinux phase II and phase III trials, indicate that selective antifactor Xa activity may improve the efficacy:safety ratio of antithrombotic therapies for the prevention of venous thromboembolism in high-risk major orthopedic surgery.

Topics: Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Heparin; Humans; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Thromboembolism

Hip fracture surgery carries a high risk of venous thromboembolism and, until recently, was poorly investigated. The efficacy and safety of fondaparinux, a new synthetic antithrombotic, were investigated in two large, thromboprophylaxis studies. Results of the Penthifra study, which was a randomized, double-blind phase III trial, showed that 1 week of fondaparinux, compared with enoxaparin, significantly reduced venous thromboembolic events from 19.1% to 8.3% (relative risk reduction: 56.4%; P<.001) without increasing bleeding risk. Penthifra Plus results showed that extending fondaparinux prophylaxis from 1 to 4 weeks was well tolerated and, compared to placebo, significantly reduced delayed venous thromboembolism events from 35% to 1.4% (relative risk reduction: 95.9%; P<.001). Based on these findings, 4-week fondaparinux treatment may become the standard thromboprophylaxis after hip fracture surgery.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Clinical Trials, Phase III as Topic; Drug Administration Schedule; Enoxaparin; Female; Fondaparinux; Fracture Fixation, Internal; Hip Fractures; Humans; Incidence; Injury Severity Score; Male; Middle Aged; Polysaccharides; Postoperative Care; Postoperative Complications; Postoperative Hemorrhage; Primary Prevention; Prognosis; Radiography; Randomized Controlled Trials as Topic; Sex Factors; Survival Rate; Thromboembolism; Treatment Outcome

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Proper administration of antithrombotic and antiplatelet drugs after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and renal insufficiency is a challenging task. In this study, we utilized Fondaparinux and Tirofiban (either separately or combined) to treat post-PCI patients with ACS and concurrent renal insufficiency. The patients were followed-up for 1 year. We observed that combined treatment led to a higher number of significant therapeutic effects and better reduced the frequency of bleeding events. Our findings indicate that combined antithrombotic and antiplatelet treatment improves the prognosis in patients with ACS and renal insufficiency who received PCI treatment.

Topics: Acute Coronary Syndrome; Aged; Anticoagulants; Drug Combinations; Female; Fondaparinux; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Polysaccharides; Postoperative Complications; Renal Insufficiency; Tirofiban; Tyrosine

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

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

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

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

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

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

We sought to assess the feasibility of comparing the efficacy and safety of fondaparinux versus heparin for prevention of graft failure and major CV events in patients undergoing coronary artery bypass grafting (CABG). Patients undergoing CABG were randomized to receive postoperative injections of fondaparinux or heparin in-hospital. After discharge, the fondaparinux group received fondaparinux and the heparin group received placebo injections for 30 days post surgery. Efficacy outcomes were graft failure, death, MI, and stroke at 30 days. Safety outcomes were bleeding, transfusion, and reoperation. 100 patients were recruited, 99 were randomized, 49 received fondaparinux and 50 received heparin. CT angiography was performed in 97% of patients. 188 grafts in the treatment group and 189 grafts in the heparin group were imaged. A similar proportion of patients treated with fondaparinux compared with heparin had at least one occluded graft (18.8% fondaparinux vs. 14.9% heparin, P = 0.62) and a similar number of grafts were occluded in each treatment group (all grafts: 4.8% vs. 4.8%, P = 0.99; saphenous vein grafts 4.2% vs. 4.2%, P = 0.98). There was no difference between treatment groups in death, MI, stroke, bleeding events, or reoperation. One in 10 patients undergoing CABG had at least one occluded graft at 30 days and one in 20 grafts is occluded by 30 days. Fondaparinux appears to be a safe alternative to heparin after CABG and it is feasible to conduct a definitive RCT using CT angiography to evaluate the effect of fondaparinux treatment on graft patency.

Topics: Aged; Aged, 80 and over; Anticoagulants; Coronary Artery Bypass; Double-Blind Method; Female; Fondaparinux; Heparin; Humans; Male; Middle Aged; Polysaccharides; Postoperative Complications; Prospective Studies; Time Factors

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

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

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

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

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

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

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

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

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

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

The targeted mechanism of factor Xa inhibition has been studied extensively, initially as prophylaxis for venous thromboembolism (VTE) in the orthopedic surgical setting. Future therapeutic directions for selective factor Xa inhibition in the management of other thrombotic diseases are discussed. Thromboembolic diseases can occur in the venous or arterial sides of the circulatory system. Factor Xa inhibition is a targeted approach to anticoagulation that resulted from significant advances in our understanding of the coagulation cascade. The factor Xa inhibitor fondaparinux has been studied extensively in the orthopedic surgical setting for the prophylaxis of VTE. Current investigations that are under way or completed evaluate the efficacy and safety of fondaparinux for the management of various thrombotic diseases. The future development of fondaparinux resides primarily in three therapeutic areas: prevention of VTE, treatment of VTE, and treatment of acute coronary syndromes. For the prevention of VTE, fondaparinux has been studied as extended prophylaxis following hip fracture surgery (PENTHIFRA Plus), for use in high-risk abdominal surgical patients (PEGASUS and APOLLO), and for use in medical patients (ARTEMIS). Studies evaluating fondaparinux for the treatment of VTE are part of the large MATISSE clinical program (MATISSE DVT and MATISSE PE). Fondaparinux was investigated in phase 2 studies for the treatment of acute coronary syndromes, including acute ST-segment myocardial infarction (PENTALYSE) and unstable angina (PENTUA). Encouraging data from these trials are the basis for phase 3 programs in this area (MICHELANGELO). The orthopedic prophylactic and nonorthopedic clinical programs for fondaparinux in the management of thrombosis support the concept that targeted inhibition of coagulation is an effective advance in antithrombotic therapy.

Topics: Adult; Aged; Aged, 80 and over; Antithrombin III; Female; Fondaparinux; Forecasting; Humans; Male; Middle Aged; Polysaccharides; Postoperative Complications; Thromboembolism

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia and thrombosis are potentially fatal adverse reactions to heparin therapy caused by the formation of polyclonal antibodies against the platelet factor 4-heparin complex. Fatal limb and organ damage or death may occur as a result of this immunological drug reaction. Described in this case report is the management of a patient who developed HIT after undergoing a MitraClip transcatheter mitral valve repair. The aim was to encourage clinicians to pay special attention to a frail patient who receives heparin therapy and to advise clinicians that clinical scores and laboratory tests should be used as a complement for certain diagnosis. The decision about continuation or cessation of heparin therapy is an important cornerstone for hospitalized patients with HIT.

Topics: Factor Xa Inhibitors; Fibrinolytic Agents; Fondaparinux; Heart Valve Prosthesis Implantation; Heparin; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Polysaccharides; Postoperative Complications; Thrombocytopenia

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

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

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

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

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

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

Edoxaban, an oral direct factor Xa inhibitor, was developed and approved for anticoagulant thromboprophylaxis after total knee arthroplasty (TKA). We retrospectively investigated the postoperative anemia by oral administration of edoxaban 30 mg compared with fondaparinux 2.5 mg in TKA patients. Two hundred twenty nine patients who underwent TKA in National Hospital Organization Okayama Medical Center from July 2010 to June 2012 were divided into two groups; pre and post approval of edoxaban: fondaparinux-group (F-group) and edoxaban-group (E-group). As the primary endpoint, the frequency of postoperative anemia was evaluated. Blood coagulation values and relations between these parameters and postoperative anemia were also investigated. The frequency of postoperative anemia was significantly higher in E-group than F-group patients (52.7% vs. 37.8%; p<0.05). Hemoglobin (Hgb) levels were decreased with the peak at postoperative day (POD) 3 in both groups, and the change of Hgb values from POD1 (ΔHgb) was significantly increased in the E-group (p=0.04). At each POD, prothrombin time (PT) and international normalized ratio of PT (PT-INR) prolonged from the preoperative day in E-group were significantly higher than F-group. Additionally, PT and PT-INR in the E-group at POD3 were significantly prolonged in patients with postoperative anemia and the sensitivity of cut-off values to predict postoperative anemia was superior to the activated partial thromboplastin time (APTT). Thus, as the frequency of postoperative anemia tended to be higher in E-group, edoxaban 30 mg might require vigilance, and prolonged PT and PT-INR could potentially predict edoxaban-associated postoperative anemia after TKA.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anemia; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Injections, Subcutaneous; International Normalized Ratio; Male; Partial Thromboplastin Time; Polysaccharides; Postoperative Complications; Prothrombin Time; Pyridines; Thiazoles; Thrombosis

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

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

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

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 present a case of heparin induced thrombocytopenia in a patient treated with enoxaparin.. A case of heparin-induced thrombocytopenia was examinated with a detailed platelet count analysis over the time and with detection of platelets antibodies.. The detection of platelet antobodies and the recovery of platelet count after cessation of enoxaparin strongly support the diagnosis of heparin-induced thrombocytopenia (HIT).. HIT is a severe side effects of heparin administration. It is more frequent in patients treated with unfractionated heparin however can also be induced by low molecular weight heparin. Guideline suggests the cessation of heparin administration and the treatment of patients with fondaparinux.. Enoxaparin, Heparin induced thrombocytopenia, Thrombocytopenia.. Scopo dell’articolo è la presentazione di un caso di trombocitopenia indotto dall’eparina in un paziente trattato con enoxaparine. L’osservazione in questione è stata analizzata in dettaglio con ripetute conta delle piastrine e con l’individuazione di anticorpi antipiastrine. La scoperta degli anticorpi-antipiastrine ed il restauro della conta piastrinica dopo la cessazione della somministrazione dell’enoxaparina è alla base della diagnosi di trombocitopenia indotta dall’eparina. Questo tipo di trombocitopenia è un grave effetto collaterale della somministrazione di eparina, ed è più frequente nei pazienti trattati con eparina non frazionata, ma può comunque essere provocata dalla somministrazione di eparina a basso peso molecolare. Le linee guida suggeriscono di sospendere la somministrazione di eparina e di trattare i pazienti con fondaparinux.

Topics: Anticoagulants; Autoantibodies; Drug Substitution; Duodenal Neoplasms; Enoxaparin; Female; Fondaparinux; Humans; Immunoglobulin G; Intensive Care Units; Middle Aged; Pancreatitis; Polysaccharides; Postoperative Complications; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a rare but severe prothrombotic disorder of heparin treatment that leads to a decline in platelet count and thrombotic complications. If HIT is suspected, then heparin should be stopped and an alternative anticoagulant started. Fondaparinux is a factor Xa-inhibitor that is not FDA-approved for this condition, but preliminary experience in HIT patients has been reported in the literature. The present study describes an experience of anticoagulation management with fondaparinux in postoperative cardiac surgery patients.. Retrospective study.. Tertiary hospital.. Patients who had undergone cardiac surgery from October 2009 to June 2012.. After HIT was suspected clinically, PaGIA and ELISA test were performed in all patients to diagnose HIT. In the patients included, anticoagulation was managed with a low dose of fondaparinux and daily monitoring of platelet count and anti-Xa level.. Of a total of 1,338 postoperative cardiac surgery patients, 15 patients were included (1.1%). Twelve of the 15 patients with HIT presented with renal failure and were under continuous renal replacement therapy. Two major bleeding events occurred during fondaparinux treatment, although platelet count and anti-Xa activity remained within the normal range. No thrombotic episodes were diagnosed.. With daily monitoring of anti-Xa activity, fondaparinux appeared to be a good alternative to heparin in the study group; however, randomized clinical trials are needed to establish the safety and efficacy of this drug in critically ill, previously HIT patients.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Factor X; Female; Follow-Up Studies; Fondaparinux; Heart Diseases; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Platelet Count; Polysaccharides; Postoperative Complications; Retrospective Studies; Thrombocytopenia; Thrombosis; Treatment Outcome

Thromboembolic complications such as systemic embolization and valve thrombosis are a major concern early after mechanical valve replacement; however, the benefit of anticoagulation must be weighed against the risk of early postoperative bleeding complications. Thromboembolic risk is also higher in the early postoperative period (less than 6 mo) compared with the risk in the late postoperative period. Current evidence supports the use of unfractionated heparin or low-molecular-weight heparin early after valve replacement to prevent valve thrombosis or systemic embolization but provides no recommendations for the management of patients with a history of heparin-induced thrombocytopenia (HIT), in which heparin products are contraindicated. We describe the use of fondaparinux early after aortic mechanical valve replacement in a 63-year-old, 95-kg woman with a history of HIT. Fondaparinux was initiated on postoperative day 2 at a prophylactic dose of 2.5 mg subcutaneously daily; the dose was increased to a therapeutic weight-based dose of 7.5 mg subcutaneously daily on postoperative day 3. Warfarin was initiated on postoperative day 1, and fondaparinux was continued until a therapeutic international normalized ratio was achieved. The patient was discharged from the hospital receiving warfarin alone on postoperative day 6. No signs or symptoms of thrombosis or bleeding were noted during or after fondaparinux therapy or at hospital follow-up visits. To our knowledge, this is the first case report to describe the use of fondaparinux within the first 48 hours after mechanical valve replacement in a patient with a history of HIT. This case suggests that fondaparinux may be a safe and effective option to prevent thromboembolic complications early after mechanical valve replacement when heparin products are contraindicated.

Topics: Anticoagulants; Aortic Valve; Female; Follow-Up Studies; Fondaparinux; Heart Valve Prosthesis Implantation; Heparin; Humans; International Normalized Ratio; Middle Aged; Polysaccharides; Postoperative Complications; Thrombocytopenia; Thromboembolism; Treatment Outcome; Warfarin

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Topics: Anticoagulants; Aortic Valve Stenosis; Aspirin; Drug Therapy, Combination; Fondaparinux; Heart Valve Prosthesis; Hemorrhage; Humans; Male; Middle Aged; Obesity; Platelet Aggregation Inhibitors; Polysaccharides; Postoperative Complications; Risk Factors; Thromboembolism; Time Factors; Treatment Outcome

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

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

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

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

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

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

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

Topics: Anesthesia, Epidural; Anesthesia, Spinal; Anticoagulants; Arthroplasty, Replacement, Hip; Catheterization; Fondaparinux; Humans; Lumbosacral Plexus; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Thrombosis

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

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; 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

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

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

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

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

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

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

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

Topics: Anticoagulants; Fondaparinux; Hip Fractures; Humans; Polysaccharides; Postoperative Complications; Thrombosis

Topics: Anticoagulants; Contraindications; Drug Interactions; Factor Xa Inhibitors; Female; Fondaparinux; Humans; Male; Polysaccharides; Postoperative Complications; Thromboembolism

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

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

New developments--in the form of emerging clinical settings for regional anesthesia as well as problems arising with the concomitant use of regional techniques and hemostasis-altering drugs--require the ongoing revision of safety guidelines. The annual meeting of ESRA held in Spain in 2003 saw the discussion and clarification of a variety of issues of current concern, including conclusions reached on the estimated risk of spinal hematoma when published safety guidelines are followed or not, precautions to take in epidural anesthesia during cardiac surgery, guidelines for using fondaparinux for thromboprophylaxis, the circumstances under which neuroaxial techniques can be used safely in patients under the effects of platelet aggregation inhibitors such as thienopyridine, and the application of epidural anesthesia in parturients with eclampsia who have received platelet aggregation inhibitors. Conclusions drawn at the meeting enrich and clarify certain important safety issues related to local and regional anesthesia in patients receiving antiplatelet drugs and/or anticoagulants.

Topics: Anesthesia, Conduction; Anesthesia, Epidural; Anesthesia, Obstetrical; Anesthesia, Spinal; Anesthetics; Anticoagulants; Contraindications; Extracorporeal Circulation; Female; Fibrinolytic Agents; Fondaparinux; Hematoma; Hemostasis; Humans; Intraoperative Complications; Platelet Aggregation Inhibitors; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Pregnancy; Risk Factors; Safety; Spinal Diseases; Thrombosis

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

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

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

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

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

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

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

Topics: Anticoagulants; Enoxaparin; Evidence-Based Medicine; Fondaparinux; Humans; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Thromboembolism

During the last decade, new anticoagulant drugs with anti-factor-Xa properties have been described (1, 2). Among them is fondaparinux that has been licensed recently. It is a pentasaccharide mimicking the site where heparin binds to antithrombin III (1). This new drug has produced very promising clinical results in the prophylaxis of venous thrombosis after orthopedic surgery (3). Here we report two different clinical situations in which fondaparinux has yielded a successful outcome: first, a patient with repeated cutaneus reaction to several different low molecular weight heparins (LMWH), and second, a patient with severe heparin-induced thrombocytopenia (HIT). We decided to use fondaparinux in both cases since it is commercially available in Spain and mostly because the absence of in vitro cross-reaction with heparins, as discussed later.

Topics: Abortion, Induced; Acute Kidney Injury; Adenocarcinoma; Adult; Aged; Autoimmune Diseases; Combined Modality Therapy; Drug Eruptions; Drug Hypersensitivity; Endometrial Neoplasms; Female; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Lupus Erythematosus, Systemic; Polysaccharides; Postoperative Complications; Pregnancy; Thrombophilia; Thrombosis

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

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

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

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

Topics: Clinical Trials, Phase III as Topic; Fondaparinux; Hip Prosthesis; Humans; Knee Prosthesis; Polysaccharides; Postoperative Complications; Thromboembolism; Treatment Outcome

Topics: Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Leg; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Thromboembolism

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

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

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

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

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

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

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

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

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

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

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