Use Of Fondaparinux Research Articles

Association Between the Use of Fondaparinux vs Low-Molecular-Weight Heparin and Clinical Outcomes in Patients With Non–ST-Segment Elevation Myocardial Infarction

Fondaparinux was associated with reduced major bleeding events and improved survival compared with low-molecular-weight heparin (LMWH) in a large randomized clinical trial involving patients with non-ST-segment elevation myocardial infarction (NSTEMI). Large-scale experience of the use of fondaparinux vs LMWH in a nontrial setting is lacking. To study the association between the use of fondaparinux vs LMWH and outcomes in patients with NSTEMI in Sweden. Prospective multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry involving 40,616 consecutive patients with NSTEMI who received fondaparinux or LMWH between September 1, 2006, through June 30, 2010, with the last follow-up on December 31, 2010. In-hospital treatment with fondaparinux or LMWH during the hospital stay. In-hospital severe bleeding events and death and 30- and 180-day death, MI, stroke, and major bleeding events. Logistic regression models adjusted for calendar time, admitting hospital, baseline characteristics, and in-hospital revascularization. In total, 14,791 patients (36.4%) were treated with fondaparinux and 25,825 (63.6%) with LMWH. One hundred sixty-five patients (1.1%) in the fondaparinux group vs 461 patients (1.8%) in the LMWH group experienced in-hospital bleeding events (adjusted odds ratio [OR], 0.54; 95% CI, 0.42-0.70). A total of 394 patients (2.7%) in the fondaparinux group died while in the hospital vs 1022 (4.0%) in the LMWH group (adjusted OR, 0.75; 95% CI, 0.63-0.89). The differences in major bleeding events and mortality between the 2 treatments were similar at 30 and 180 days. There were no significant differences in the number of recurrent MI and stroke events at 30 or 180 days among the 2 treatment groups. In routine clinical care of patients with NSTEMI, fondaparinux was associated with lower odds than LMWH of major bleeding events and death both in-hospital and up to 180 days afterward.

0208: Impact of fondaparinux versus enoxaparin on in-hospital bleeding and one-year death in non-ST-segment elevation myocardial infarction. FAST-MI 2010 registry

Fondaparinux is an alternative to low molecular weight heparin (LMWH) for non-ST-elevation myocardial infarction (NSTEMI) with levels of recommendation that differ according to guidelines. The aim of this study was to assess one-year survival in real world practice in NSTEMI patients participating in the French Registry of ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2010 according to the use of fondaparinux, in comparison with patients receiving enoxaparin. FAST-MI 2010 is a nationwide French registry that included 4,169 patients with acute myocardial infarction (AMI) at the end of 2010 in 213 centres (76% of active centres in France). Of those, 1,734 had NSTEMI, of whom 240 received fondaparinux and 1,027 enoxaparin. Patients receiving enoxaparin vs. fondaparinux were similar for many characteristics; especially with a similar GRACE (Global Registry of Acute Coronary Events) score (133±36 vs. 134±38). Invasive strategy was used in 69% in both groups. In-hospital bleeding was similar with both anticoagulant strategies and one-year survival was 94.6% vs. 91.7% respectively. Using fully adjusted Cox multivariate analysis, the use of fondaparinux was not associated with a reduced risk of death (hazard ratio [HR]: 1.35; 95% confidence interval [CI]: 0.70-2.51). After propensity score matching (207 patients per group), one-year survival was similar with both strategies. In this real-world cohort of NSTEMI patients, most of whom were managed invasively, there was no evidence that fondaparinux was superior to enoxaparin as regards bleeding events or one-year mortality. (FAST-MI 2010; NCT01237418)

Fondaparinux in the initial and long-term treatment of venous thromboembolism

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

Treatment options for venous thromboembolism: lessons learnt from clinical trials.

Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is a common condition associated with a significant clinical and economic burden. Anticoagulant therapy is the mainstay of treatment for VTE, having been shown to reduce the risk of death in patients with pulmonary embolism, and recurrence or extension of thrombi in patients with deep vein thrombosis during the initial treatment period. Long-term anticoagulation is indicated in some individuals with VTE, depending on individual risk of VTE recurrence and anticoagulant-related bleeding. Management of VTE in clinical practice is often complex because patients’ characteristics and treatment needs may differ considerably from those encountered in clinical trials. Current guidelines recommend the use of either low molecular weight heparins or fondaparinux overlapping with and followed by a vitamin K antagonist for the initial treatment of VTE, with the vitamin K antagonist continued when long-term anticoagulation is required. These traditional anticoagulants have practical limitations that have led to the development of direct oral anticoagulants that directly target either Factor Xa or thrombin and are administered at a fixed dose without the need for routine coagulation monitoring. This review discusses practical considerations for hospital physicians and haematologists in the management of VTE treatment, including the potential for the direct oral anticoagulants to simplify treatment.

SAfety of Fondaparinux in transoesophageal echocardiography-guided Electric cardioversion of Atrial Fibrillation (SAFE-AF) study: A pilot study

Current guidelines recommend unfractionated heparin (UFH) or low-molecular-weight heparin plus an oral anticoagulant for the prevention of thromboembolism in patients undergoing electric cardioversion of atrial fibrillation (AF). Selective factor Xa inhibitors, such as fondaparinux, which has a favourable benefit-risk profile in the prevention and treatment of venous thromboembolism and the management of acute coronary syndromes, have not been systematically evaluated in this setting. To evaluate the efficacy and safety of fondaparinux versus standard treatment in patients undergoing echocardiographically-guided cardioversion of AF. In this multicentre, randomized, open-label, controlled, two-parallel-group, phase II pilot study, patients with AF undergoing electric cardioversion following transoesophageal echocardiography (TEE) were randomized to fondaparinux or standard therapy (UFH plus vitamin K antagonist [VKA]). Patients showing an atrial thrombus in the first TEE (clot-positive) were randomized to treatment with fondaparinux or standard care for 4 weeks before cardioversion. The primary endpoint (combined rate of cerebral neurological events, systemic thromboembolism, all-cause death and major bleeding events) occurred in 3 of 174 (1.7%) patients on fondaparinux and 2 of 170 (1.2%) patients on UFH+VKA. The rate of thrombus disappearance among clot-positive patients was higher in the fondaparinux arm (11 of 14; 78.6%) than in the UFH+VKA arm (7 of 14; 50.0%). Incidences of adverse events were similar (45.4% with fondaparinux and 46.5% with UFH+VKA). In this pilot study in patients with TEE-guided cardioversion, the use of fondaparinux appeared to be well tolerated, with similar efficacy to UFH+VKA. Furthermore, a trend to greater thrombus resolution was observed.

The use of fondaparinux in pregnancy

The use of fondaparinux in pregnancy

Successful Use of Fondaparinux in a Patient with Heparin-induced Thrombocytopenia while on Extracorporeal Membrane Oxygenation after Mitral Valve Redo Surgery

In patients with respiratory failure and impairment of the left ventricle, arteriovenous extracorporeal membrane oxygenation (ECMO) offers further therapeutic options. Systemic anticoagulation is mandatory and heparin is routinely administrated. However, repeated exposure to heparin may cause heparin-induced thrombocytopenia (HIT) and carries a risk of thrombotic mortality and morbidity. We present a patient who developed HIT during ECMO support and was treated successfully and safely by fondaparinux. Fondaparinux can be used for thromboembolic treatment or prophylaxis in a patient with HIT.

Successful Use of Fondaparinux Early After Mechanical Aortic Valve Replacement in a Patient with a History of Heparin‐Induced Thrombocytopenia

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.

Frequent off-label use of fondaparinux in patients with suspected acute heparin-induced thrombocytopenia (HIT) – findings from the GerHIT multi-centre registry study

IntroductionIn life-threatening immune heparin-induced thrombocytopenia (HIT), treatment with an approved non-heparin anticoagulant is essential. However, off-label use with fondaparinux has been reported in the literature. The study aim was to collect data on “real-life” management of patients with suspected acute HIT regarding diagnostic and therapeutic strategies. Patients and MethodsIn a national multi-centre registry study, patients with a 4T’s HIT-probability score of ≥4 points and treatment with at least one dose of (A)rgatroban, (L)epirudin, (D)anaparoid, or (F)ondaparinux were retrospectively evaluated. ResultsOf 195 patients, the 4T’s scores were 4/5/6/7/8 points in 46 (23.6%)/50 (25.6%)/74 (38.0%)/13 (6.7%)/7 (3.6%) patients, respectively. During heparin therapy, 47 (24.1%) thromboembolic events, 5 (2.6%) skin lesions, 1 (0.5%) amputation, 24 (12.3%) Hb-relevant bleedings, and 2 (1.0%) fatalities occurred. A functional heparin-induced platelet activation assay was performed in 96.9%, a platelet factor 4/heparin-dependent enzyme immunoassay in 89.2%, a particle gel immunoassay in 12.3%, and a serotonin-release assay in none of the patients. Argatroban was used in 16.4%, lepirudin in 2.1%, danaparoid in 23.6%, fondaparinux in 40.0% of the patients; the sequential therapy strata were: AF (5.6%), DA (5.6%), DF (2.6%), DL (2.1%), ADF (1.5%), and DFL (0.5%). ConclusionsThe current diagnostic laboratory strategy for suspected HIT is mostly (>96%) based on the recommended 2-step strategy (immunoassay plus functional assay). However, there is a wide fondaparinux off-label use (up to 50.3%) for suspected HIT, even in those patients with a high clinical pretest probability. Efficacy and safety of fondaparinux for HIT-treatment require further evaluation.

Thromboprophylaxis with fondaparinux in high-risk postoperative patients with renal insufficiency.

Fondaparinux is an antithrombin-dependent factor Xa inhibitor that is used for thromboprophylaxis of patients undergoing hip fracture surgery, hip or knee replacement, or abdominal surgery. It is cleared by the kidney and should be used with caution in patients with renal impairment and avoided in patients with severe renal insufficiency. Recently, several studies have demonstrated that a lower dose of fondaparinux in patients with moderate renal impairment appears to be safe and effective. The purpose of this study was to obtain pharmacokinetic and clinical data on the use of prophylactic fondaparinux in patients with renal insufficiency undergoing major abdominal surgery for cancer (n=8) or orthopedic surgery (n=1). Anti-factor Xa levels were obtained, and a published population pharmacokinetic model for fondaparinux was fit to the data. The data were analyzed using NONMEM software. Fondaparinux did not appear to accumulate in these patients, even when the drug was administered for up to twelve days. Pharmacokinetic analysis revealed that the apparent clearance in this population, who were primarily undergoing cancer surgery, was similar to prior studies in orthopedic surgery patients. In contrast, lower estimates were obtained for volume of distribution and absorption rate constant parameters. None of the patients sustained a hemorrhagic complication attributable to fondaparinux. One patient developed hypoxia in the setting of transient atrial fibrillation and clinical suspicion for pulmonary embolism, but this was not confirmed radiographically. These results support the use of 1.5mg of fondaparinux every 24hours for thromboprophylaxis in patients with renal insufficiency undergoing high-risk surgical procedures.

Use Of Fondaparinux For Venous Thromboembolism Prophylaxis In Critically Ill Adult Patients With Moderate Renal Insufficiency

Introduction Fondaparinux, a selective activated Factor Xa inhibitor, is a parenteral anticoagulant primarily excreted by the kidneys. Renal insufficiency (RI), commonly encountered in the critically ill, has been shown to portend an increased risk of bleeding than in normal healthy adults. In comparison to the low molecular weight heparin dalteparin, fondaparinux has been shown to be superior for the prevention of post-surgical venous thromboembolism (VTE), however an increased rate of nonfatal bleeding has been observed. Recently, data has emerged supporting empiric dose reductions in patients with moderate RI, defined as a creatinine clearance (CrCl) between 30 and 50 mL/min. Overall, the data supporting appropriate use of fondaparinux in patients with RI is lacking. This retrospective, single center study describes our experience using prophylactic fondaparinux in critically ill patients with moderate RI. Methods We report our experience utilizing fondaparinux in a mixed medical and surgical, critically ill adult population with moderate RI. The site examined was UF Health; an 852-bed sized tertiary care hospital in Gainesville, Florida between 2006 and 2012. Moderate RI was defined as a CrCl between 30 and 50 mL/min calculated by the Cockcroft/Gault equation. Only patients treated with fondaparinux for prophylaxis of VTE were included, patients treated for other indications were excluded. Doses, dose frequency and dose adjustments were documented. If patients had anti-Xa level monitoring these values were recorded. Timing of anti-Xa levels drawn with respect to fondaparinux dosing was also noted. The primary end point of the study was the rate of clinically significant bleeding events in patients receiving at least 72 hours of fondaparinux. Clinically significant bleeding was defined as transfusion of at least two units of packed red blood cells within 48 hours of a documented bleeding event or the workup of bleeding with endoscopy or imaging. Bleeding events were screened by ICD-9 codes and validated via chart review, incidence of VTE was also noted. Results Sixty-fourpatients met inclusion criteria between October 2006 and November 2012. Two patients (3.1%) experienced clinically significant bleeding events as per our definition, both in the form of gastrointestinal bleeding. Empiric dose reductions occurred in 8 (12.5%) patients, this occurred in the form of every other day administration or dose reduction using fondaparinux 1.25mg daily. Nine (14%) patients were monitored with anti-Xa levels, none of these patients encountered bleeding events. The median anti-Xa level was 0.5 mcg/mL, which is in the target prophylactic range for in our lab. The median time interval after last dose of fondaparinux to anti-Xa level measurement was 4 hours. Seven (10.9%) patients had VTE diagnoses prior to the initiation of prophylactic fondaparinux. No patients suffered a VTE event after treatment with prophylactic fondaparinux in our data set. Conclusion We report a cohort of patients with moderate RI receiving fondaparinux for the prevention of VTE. The incidence of clinically significant bleeding was 3.1%. The risk of VTE was low, no patients suffered from a VTE after treatment with fondaparinux in our data set. The rate of bleeding is slightly higher compared to patients with normal renal function. Our experience over this 6 year period supports the notion that RI portends an increased risk of bleeding with the use of fondaparinux. Further prospective studies are needed to determine the safety and efficacy of empiric fondaparinux dose reductions in patients with RI and end stage renal disease. Anti-Xa monitoring may help reduce the risk of bleeding in this patient population by identifying those patients in whom a dose reduction may be beneficial. Disclosures: No relevant conflicts of interest to declare.

Clinical experience with fondaparinux in antiaggregate patients undergoing total hip and knee arthroplasty

Patients undergoing total hip arthroplasty or total knee arthroplasty have a high risk for post-operative venous thromboembolism. The current study addressed the use of fondaparinux post-operatively in 556 patients with antiplatelet therapy in order to prevent deep vein thrombosis as well as demonstrate efficacy in preventing arterial thrombotic events. Results provided evidence for a safe and effective prophylaxis strategy, involving the change from low molecular weight heparin pre-operatively to fondaparinux postoperatively. Also, fondaparinux proved effective as a unique post-operative therapy in the prevention of venous thromboembolism with no adverse effects, such as major bleeding or arterial thrombosis in patients with pre-operative antiplatelet therapy.

Fondaparinux as an alternative to vitamin K antagonists in haemodialysis patients

Accelerated vascular calcification and increased risk of calciphylaxis can be a reason to restrict the use of vitamin K antagonists in dialysis patients. We describe the use of fondaparinux, a prototype indirect factor Xa inhibitor, as an alternative anticoagulant to coumarin derivatives in dialysis patients. In this case series, we included six chronic haemodialysis patients treated with vitamin K antagonists. Low-molecular-weight heparin given as anticoagulant during dialysis was replaced by fondaparinux. Anti-Xa activity was regularly measured pre- and postdialysis to adapt the dose of fondaparinux. Adequate continuous anticoagulation and circuit patency were registered by evaluating clotting in the bubble trap and dialyser membrane at the end of dialysis. Anticoagulation with fondaparinux at a starting dose of 2.5 mg resulted in an effective anticoagulation in the majority of dialysis sessions. Although median predialysis anti-Xa levels were significantly lower [0.36 IU/mL (0.30-0.42 IU/mL) (P < 0.0001)] than postdialysis levels [0.75 IU/mL (0.65-0.80 IU/mL)], predialysis anti-Xa levels were sufficient to limit the risk of thromboembolism. After an initial period of gradually increasing anti-Xa levels due to accumulation of fondaparinux, stable levels were achieved. Haemodialysis without clotting problems was possible in 96% of the sessions (clotting score ≤1), whereas two episodes (2/459 dialysis sessions) of major clotting were observed, defined as clotting of the extracorporeal circuit necessitating premature termination of the procedure. We demonstrated that fondaparinux is a valuable anticoagulant for patients dialysed with low-flux membranes in need of continuous anticoagulation.

Le syndrome coronarien aigu chez le sujet âgé : expérience du centre hospitalier d’Aix-en-Provence

IntroductionCardiovascular causes are the first causes of death in elderly patients. Nevertheless, elderly patients are underrepresented in randomized studies of acute coronary syndromes although treatment of ACS for elderly patients has specificities that need special attention. Methods and resultsTo discuss these specificities, we realized a retrospective study involving patients aged more than 75years old and admitted for ACS in the cardiology department of Aix-en-Provence General Hospital in the first six months of 2010 (Group A) and 2012 (Group B) which we compared. Initial presentation was chest pain in only 78.6% of Group A versus 81.6% in Group B (NS), renal insufficiency was found in 41.4% of the patients of Group A versus 50.5% of the patients in Group B (NS), anaemia was found in 34.3% of Group A patients versus 40.2% of Group B (NS), invasive strategy is less systematic with 74.2% of Group A patients having a revascularization versus 73.6% of Group B (NS), Drug Eluting Stents were less frequently used with 14.3% of Group A patients versus 14.7% of Group B (NS), radial access was used for angioplasty in 61.2% of Group A patients versus 80.2% of Group B (P=0.02), unfractioned heparin was used in 74.3% of the cases in Group A versus 68% in Group B (NS). Discussion and conclusionAcute coronary syndrome of the elderly patients has numerous specificities, first there are frequent unusual presentation making diagnosis more difficult, second they have frequent co morbidities making them frail patients with higher risk of hemorrhagic complications and lesser tendency to invasive evidence based treatment. In the absence of specific recommendations, their treatment should not differ from younger patients. This work allowed us also to evaluate our professional practices in order to improve them; we note a positive evolution with the significant raise in the use of radial access, invasive strategy though should be more systematic and use of low molecular weight heparin and Fondaparinux should be more frequent.

Fondaparinux‐associated heparin‐induced thrombocytopenia

Large licensing trials did not find any association between the use of fondaparinux and the development of heparin-induced thrombocytopenia (HIT). Fondaparinux is in fact recommended as an option for the management of HIT. Since the first report of fondaparinux-associated HIT in 2007, additional reports have been published. However, the rarity of these cases, differences in case definition, and lack of larger case series have prevented better understanding of this disease. The objective of this study was to determine the clinical manifestations of fondaparinux-associated HIT, the predictive value of pretest probability (4Ts) scoring system, and the outcomes associated with current management. Using several search terms, we reviewed all cases of fondaparinux-associated HIT reported and indexed in PubMed till May 2013. All references were also checked for additional reports. We categorized the cases of fondaparinux-associated HIT as confirmed, probable, and possible based on our case definition. A total of eight cases of fondaparinux-associated HIT were identified. Fondaparinux-associated HIT occurred in the setting of pro-inflammatory state, prior HIT, or exposure to heparin products. Bilateral adrenal hemorrhage or infarct, reflecting hypercoagulability or disseminated intravascular coagulation, was seen in 25% of patients. The pretest probability (4Ts) scoring system used for HIT appears to correctly risk stratify all the cases. Although functional assays can be used for the diagnosis, in the presence of recent exposure to heparin products, only the demonstration of fondaparinux-dependent platelet activation should be considered confirmatory. Non-heparin anticoagulants are effective therapy; however, one-third of the patients had poor outcomes. The risk of fondaparinux-associated HIT, although low is real, which along with documented cases of fondaparinux failure mandate its cautious use in the management of HIT.

Efficacy and Safety of Off‐Label Use of Fondaparinux in the Management of Heparin‐Induced Thrombocytopenia with Thrombosis in an Elderly Woman

Type II heparin‐induced thrombocytopenia (HIT) represents the most common immune‐mediated adverse drug reaction (ADR), during treatment with unfractionated heparin (UFH) or low molecular weight heparins (LMWHs). The frequency of HIT is about 2–3% in surgical divisions (e.g., Cardiac Surgery and Orthopedics) and about 0.5–1% in medical divisions (e.g., Internal Medicine). HIT can develop in 5–10 days after the beginning of heparin and it is induced by the production of antibodies targeting a molecular complex of both “self” protein, that is platelet factor 4 (PF4), and heparin. This induces platelet activation as well as increased thrombin production, that result in a higher risk of venous or arterial thrombosis. When thrombosis is identified, HIT is called HIT‐ associated thrombosis (HITT). Identification of a decrease in platelet count represents the first step in the diagnosis of HIT. However, other clinical and laboratory tests, such as 4Ts score serotonin‐release assay (SRA) and measurement of heparin/PF4 antibodies, must be also used. 4Ts score is a clinical scoring system used to estimate the pretest probability of HIT1, based on its characteristic features (Thrombocytopenia, Timing, Thrombosis) and absence of oTher explanation(s). 4Ts score (Table 1) is also used in the pharmacological management of HIT: score 3 continue heparin, score >4 change heparin to non‐heparin anticoagulants. Among non‐heparin anticoagulants, only lepirudin and argatroban, direct thrombin inhibitors (DTIs), are approved in the treatment of HIT. Another DTI, bivalirudin, is indicated in patients undergoing percutaneous coronary interventions. Danaparoid, a factor Xa inhibitor, is not currently available in Italy, but it is approved for treatment and prevention of HITT in Canada, continental Europe, Australia, New Zealand, and Japan. Finally, fondaparinux sodium, a synthetic antithrombin‐binding pentasaccharide with exclusive anti‐factor Xa activity, has shown favorable results in HIT, although in Italy it is off‐label for this indication. In this paper, we report a case of HITT during treatment with a LMWH, that was successfully treated with an off‐ label administration of fondaparinux sodium.

Impact of an Immunoglobulin G–Specific Enzyme‐Linked Immunosorbent Assay on the Management of Heparin‐Induced Thrombocytopenia

To evaluate whether using an immunoglobulin G (IgG)-specific platelet factor 4 (PF4) test reduces the rate of positive PF4 results and has an impact on prescribing practices of nonheparin anticoagulants (direct thrombin inhibitors and fondaparinux) in patients assessed for heparin-induced thrombocytopenia (HIT). Single-center prospective cohort study with a historical control group. Large academic medical center. A total of 672 patients assessed for HIT. Patients were assessed for HIT by using either an IgG-specific PF4 enzyme-linked immunosorbent assay (ELISA; 336 patients) or a nonspecific PF4 ELISA (336 patients; historical control group). No significant difference was noted in the proportion of patients with a low, intermediate, or high risk of HIT based on the 4Ts pretest clinical scoring system. The PF4 ELISA was positive in 6.9% versus 11.3% of patients (p=0.04) in the IgG-specific and nonspecific cohorts, respectively. A smaller proportion of patients were prescribed a direct thrombin inhibitor in the IgG-specific cohort (19.4% vs 25.9%; p=0.04). No significant difference in fondaparinux use was noted between the cohorts. The duration of direct thrombin inhibitor therapy, bleeding events, hospital length of stay, and in-hospital mortality was similar in both cohorts. Use of an IgG-specific PF4 ELISA was associated with a lower rate of positive PF4 test results. Direct thrombin inhibitor prescribing was also significantly lower during the time period where the IgG-specific PF4 ELISA was used, with no significant differences noted in safety outcomes.

Fondaparinux

AIM OF THE STUDY To review the best evidence-based knowledge about the clinical pharmacology and use of fondaparinux. DESIGN OF THE STUDY Narrative review. RESULTS Fondaparinux is a synthetic pentasaccharide anticoagulant that binds selectively with high affinity to antithrombin and catalyses the inactivation of factor Xa, which results in a dose-dependent inhibition of thrombin generation. Fondaparinux does not bind to platelets or inhibit platelet aggregation, does not cross-react with antibodies to heparin-PF4 complexes (HIT antibodies) and has no effects on the activated partial thromboplastin time, prothrombin time and antithrombin levels. Fondaparinux shows a linear and highly predictable pharmacokinetic profile in humans, with very limited intraindividual and interindividual variability, which makes routine monitoring and dose adjustments unnecessary for the majority of the population. After subcutaneous iniection fondaparinux undergoes complete and dose-independent absorption; it is not significantly metabolized by the liver and does not interfere with cytochrome P450-mediated transformation of other drugs. Fondaparinux is almost entirely excreted unchanged in the urine with a half-life of approximately 17 hours, allowing for once-daily dosing. Its plasma clearance is reduced in patients with moderate or severe renal insufficiency. In the clinical trials and post-marketing surveillance fondaparinux shows an excellent tolerability profile, with a low incidence of major bleeding across a wide dose range and no cases of severe thrombocytopenia or heparin-induced thrombocytopenia (HIT). CONCLUSIONS Fondaparinux has been approved in many countries for use in thromboprophylaxis after major orthopedic surgery and in medical patients, and for the treatment of sintomatic venous thromboembolism (deep venous thrombosis and hemodynamically stable pulmonary embolism) and acute coronary syndromes (unstable angina, and acute miocardial infartion, with or without ST elevation). In these clinical settings fondaparinux is at least as effective and safe as unfractionated heparin or low molecular weight heparins, and may be easier to use.

Safety of Fondaparinux Versus Enoxaparin After TKA in Japanese Patients

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

A rare case of fondaparinux-induced major bleeding in postmenopausal woman prescribed for non-ST segment elevation Ml

Fondaparinux sodium is a synthetic, sulfated pentasaccharide, selective factor Xa inhibitor, a safe and effective antithrombotic agent indicated for preventing thrombus formation in patients with acute coronary syndromes, including those with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina. Major bleeding is rarely known to exist with the use of fondaparinux and to best of our knowledge there exist no isolated case report presenting with fondaparinux-induced major bleeding prescribed for recently diagnosed NSTEMI. The case report highlights, a need for clinicians to have a sound understanding of anticoagulant pharmacology, dosing, toxicity, individualized approach, and predicting the risk of bleeding before they are prescribed to advancing age persons.