Use Of Fondaparinux In Patients Research Articles

PB0436 Long-Term Use of Fondaparinux in Patients with Thrombotic Antiphospholipid Syndrome - A Retrospective Audit of Clinical Outcomes

PB0436 Long-Term Use of Fondaparinux in Patients with Thrombotic Antiphospholipid Syndrome - A Retrospective Audit of Clinical Outcomes

Novel fondaparinux protocol for anticoagulation therapy in adults with renal failure and suspected heparin-induced thrombocytopenia: a retrospective review of institutional protocol

IntroductionThe literature recommends against the use of fondaparinux in patients with kidney failure and dialysis as it may, with repeated dosing, accumulate and put patients at risk of bleeding. The management of patients with thrombosis in the presence of heparin-induced thrombocytopenia HIT requires the introduction of an alternative anticoagulant like bivalirudin or argatroban. When these drugs are not available, fondaparinux, remains the only alternative. In similar scenarios, there are few studies addressing how to administer it. MethodsWe developed a protocol for fondaparinux in patients with renal failure where pharmacokinetic parameters are altered, and levels changed only after hemodialysis or in cases of residual renal activity. Patients received a full first dose except for high risk of bleeding. We targeted a peak anti-factor Xa activity level of 0.6–1.3 units/ml and changed the subsequent dose accordingly. Furthermore, we monitored the patients for signs of bleeding, a drop in hemoglobin level, or clinical signs of thrombosis. DiscussionWe described 10 patients with kidney failure and suspected HIT taking fondaparinux. All the patients achieved therapeutic anti-factor Xa activity levels. However, one developed new-onset venous thromboembolism (VTE) despite therapeutic anti-factor Xa levels. Another patient experienced a bleeding episode. We believe that these two patients developed complications due to their medical conditions rather than the use of fondaparinux.ConclusionFondaparinux can be safely used in kidney failure using our protocol. However, despite its safety profile and relative success, this case series was small. More robust studies need to be conducted prior to drawing conclusions.

Effective use of fondaparinux in patient with unresponsiveness to nadroparin

Fondaparinux exhibits a similar mechanism of action as LMWH. Since both of these drugs bind to antithrombin and increase its affinity to factor Xa, fondaparinux is not expected to be an effective alternative anticoagulant to LMWH in case of LMWH resistance. We report on a case of effective anticoagulation using fondaparinux following total unresponsiveness to high doses of nadroparin administered twice daily, as confirmed via repeated anti-Xa measurements. The antithrombin levels were within the normal range. To the best of our knowledge, this is the first report of the effective use of fondaparinux in the case of unresponsiveness to LMWH.

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.

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.

Successful use of fondaparinux in a patient with a mechanical heart valve replacement and a history of heparin-induced thrombocytopenia

The development of heparin-induced thrombocytopenia (HIT) is an antibody-mediated clinicopathologic syndrome. The resultant thrombocytopenia and thrombosis can be severe and life-threatening. Fondaparinux is a parenteral factor Xa inhibitor used for venous thromboembolism prevention and treatment. Fondaparinux has minimal affinity for platelet factor 4, making it an alternative agent to unfractionated heparin (UFH) and low-molecular weight heparin (LMWH) and a plausible consideration for patients with a history of HIT. The use of fondaparinux in patients with mechanical heart valve replacement and a history of HIT has never been discussed in the literature. We report on the case of a patient with a mechanical aortic heart valve replacement and a history of HIT who was successfully bridged postoperatively with fondaparinux. While there is currently no literature to support the use of fondaparinux in patients with mechanical heart valves, this drug may offer an option for management of such patients who cannot use heparin products. However, further clinical investigations are warranted to confirm both the safety and efficacy of this agent in the mechanical heart valve population.

Routine use of fondaparinux in acute coronary syndromes: A 2-year multicenter experience

Fondaparinux has recently been approved in patients with acute coronary syndromes. The primary aim of this study was to describe the changes in use of anticoagulants between January 2006 and December 2007. The secondary aim was to compare 30-day mortality and rate of a combined end point (30-day death or major bleeding) according to the initial and final anticoagulant agent used. The rates of use of unfractionated heparin (UFH), enoxaparin, and fondaparinux were compared by periods of 1 month in a multicenter registry. The initial anticoagulant (first used at admission), the final anticoagulant (last used during hospitalization), and switches in anticoagulation were recorded. Temporal trends in monthly use of each anticoagulant were assessed; 30-day mortality rates and the combined end point were compared according to initial and final anticoagulant. Among 2,874 patients included, the first anticoagulant used was UFH in 26%, enoxaparin in 59%, and fondaparinux in 15%. Respective figures for final anticoagulant were 17%, 56%, and 27%. Although 3 centers did not use fondaparinux (community centers with catheterization laboratory), the overall rate of use of fondaparinux, as initial and final anticoagulant, increased at the expense of the use of enoxaparin. We observed a growing proportion of patients with a switch from UFH to either enoxaparin or fondaparinux, ranging from 5% at the beginning to 25% at the end of the study. Patients treated with UFH were older, had more comorbidities, were at higher risk, and received fewer guidelines-recommended treatments. In patients submitted to angioplasty and treated with fondaparinux, a bolus of 60 IU/kg of UFH was added. After adjustment, 30-day mortality and combined end point rates were higher in patients treated with UFH. Irrespective of the type of acute coronary syndromes, patients treated with enoxaparin or fondaparinux had similar outcomes. Between 2006 and 2007, the use of fondaparinux in patients with acute coronary syndromes increased considerably, either because it was used instead of enoxaparin or because of a switch from UFH. Adjusted mortality in patients treated with fondaparinux was lower than with UFH and similar to enoxaparin.

Cost Effectiveness of Fondaparinux in Non-ST-Elevation Acute Coronary Syndrome

Fondaparinux has been shown to reduce the risk of major bleeding and 30-day mortality compared with enoxaparin, in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). However, its cost effectiveness is not well known. To evaluate the effectiveness and economic attractiveness of fondaparinux relative to enoxaparin in patients with NSTE-ACS treated with triple antiplatelet therapy and early (non-urgent) invasive strategy. The decision model compares two alternative strategies: subcutaneous (SC) enoxaparin (1 mg/kg 12 hourly) versus SC fondaparinux (2.5 mg/day) in NSTE-ACS patients pre-treated with triple antiplatelet therapy and early revascularization. Cost-effectiveness and cost-utility analyses were performed from a healthcare perspective, based on a Markov model with a time horizon of the patient lifespan. Univariate sensitivity analysis and probabilistic (Monte Carlo) microsimulation analysis were performed. In the base-case analysis (65 years, Thrombolysis In Myocardial Infarction [TIMI] score 4), the use of fondaparinux was associated with a significant reduction in major bleeding, a slight reduction in adverse cardiac events, and minor improvements in survival and QALYs, together with a small reduction in costs. The dominance of fondaparinux over enoxaparin remained unchanged in the univariate sensitivity analyses. According to Monte Carlo simulation, fondaparinux was cost saving in 99.9% of cases. Compared with enoxaparin, the use of fondaparinux in patients with NSTE-ACS managed with an early invasive strategy appears to be cost effective, even in patients with a low risk of bleeding.

Successful management of acute thromboembolic disease complicated with heparin induced thrombocytopenia type II (HIT II): a case series

Heparin-induced thrombocytopenia type II (HIT II) is a rare immune-mediated complication of heparin. The diagnosis of HIT is considered in patients exposed to heparin, presenting with thrombocytopenia and thrombosis.We present two cases with massive pulmonary embolism and HIT, successfully treated with the administration of fondaparinux, an alternative anticoagulant, combined with the insertion of an inferior vena cava filter for the prevention of new thromboembolic events. The two cases supplement the available data of the use of fondaparinux in patients with HIT and pulmonary embolism, before further large studies establish its efficacy and safety in this group of patients. Moreover, the management of these patients reveals the need for future evaluation of the combined therapy of alternative anticoagulant agents with the placement of vena cava filters.

Extended Thromboprophylaxis with Fondaparinux after Major Orthopedic Surgery of the Lower Limbs: The EXPERT Study.

Background: The benefit-to-risk ratio of extended fondaparinux therapy was demonstrated in patients undergoing hip fracture surgery, but not in patients undergoing major joint arthroplasty. In addition, no data on the use of fondaparinux in patients in whom a continuous neuraxial/deep peripheral nerve blockade is performed are available.Objective: The EXPERT trial was an open-label, international study in patients undergoing major orthopedic surgery designed to evaluate the overall efficacy and safety of 2.5 mg fondaparinux when (I) given daily for 4±1 weeks after surgery, and (II) a “therapeutic window” is applied due to concomitant use of a neuraxial/deep peripheral indwelling catheter.Patients/Methods: Patients undergoing major orthopedic surgery received once-daily subcutaneous 2.5 mg fondaparinux starting post-surgery for 4±1 weeks. In patients with a neuraxial/deep peripheral indwelling catheter, one of the planned doses of fondaparinux was omitted, the catheter was removed 36 hours after the previous fondaparinux dose, and the next fondaparinux dose administered 12 hours after catheter removal. The primary endpoints were symptomatic venous thromboembolism (VTE) and major bleeding 5±1 weeks after surgery.Results: 5704 patients (mean age ± SD: 66.1 ± 11.9 years) were recruited into the intention-to-treat (ITT) population between July 2003 and October 2004. A neuraxial/deep peripheral indwelling catheter was placed in 1630 (28.6%) of them. They underwent surgery for total hip replacement (51.6%, n=2941), total knee replacement (39.7%, n=2263), hip fracture (6.2%, n=353), or other indications (2.6%, n=148). Fondaparinux was given for a median of 35 (range: 1–105) days. In the ITT population, the rate of adjudicated confirmed symptomatic VTE was 1.0% (54/5387). It was 0.8% (13/1535) in patients with catheter and 1.1% (41/3852) in patients without catheter, with an odds ratio of 0.79 (90% CI: 0.47 to 1.34; p=0.47) in favor of patients with a catheter. The upper limit of the 90% CI was below the predetermined criterion of 1.75 for the non-inferiority of patients with a catheter versus patients without a catheter. Comparable results were observed in the per-protocol population. The overall rate of major bleeding was 0.8% (42/5382). It was 0.9% (35/3850), and 0.5% (7/1532) in patients with and without catheter, respectively. No spinal or perineural hematomas occurred. At 5±1 weeks, 23 (0.40%) patients had died.Conclusions: 2.5 mg fondaparinux given daily for 4±1 weeks after major orthopedic surgery was both effective and safe in routine practice. This high benefit-to-risk ratio was maintained in patients in whom a 48-hour “therapeutic window” was applied due to placement of a neuraxial/deep peripheral indwelling catheter.