Haslauer, Michael

Nagler, Michael

Wuillemin, Walter

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LETTER TO THE EDITORLong-term anticoagulation with fondaparinuxin a patient with a mechanical heart valveMichael Nagler & Michael Haslauer &Walter A. WuilleminReceived: 7 December 2010 /Accepted: 14 December 2010 /Published online: 5 January 2011# Springer-Verlag 2010Dear Editor,Despite recent advances in anticoagulation therapy, thereare regular situations in clinical practice which areinadequately covered by current guidelines. These includesituations such as obesity and long-term therapy, particu-larly if vitamin K antagonists (VKA) and/or heparinderivatives are inappropriate. These situations have rarelybeen the aim of randomised controlled trials. We present acase of successful long-term treatment with fondaparinux ina patient with a mechanical heart valve, obesity andconcomitant therapy with aspirin and discuss available datain these situations.A 63-year-old male patient with obesity underwentaortal valve replacement with a mechanical prosthesisbecause of aortal stenosis. Anticoagulation with VKA wasstarted. Six weeks postoperatively, he presented with life-threatening bleeding. Investigations revealed factor IXpropeptide mutation, which made anticoagulation withVKA impossible. This rare condition causes a nearlycomplete absence of factor IX during therapy with VKA,even in the presence of a mild vitamin K deficiency [1].Therapy with low-molecular-weight heparin (LMWH)resulted in lumps at the puncture site. Failure of absorptioncould be seen in a gradual decrease in drug concentrationmeasured as anti-Xa level (initially 0.9–1.0 U/ml, reducedto 0.45–0.5 U/ml), despite increasing the dose. This adverseeffect was shown with dalteparin, enoxaparin and nadroparin.Anticoagulation was therefore started with fondaparinux. Dueto obesity (BMI, 36 kg/m2), we administered 10 mg oncedaily sc. During the next 30 months, stable drug concen-trations measured as anti-Xa of about 1.0 μg/ml wereobserved. D-dimers, measured as a degree of coagulationactivation, were always below 220 ng/ml. Regular controlsrevealed no clinical signs or symptoms of thromboemboliccomplications, and in particular, no neurological deficits.Computed tomography of the head as well as echocardiog-raphy did not reveal any thromboembolic complications. Thepatient did not experience any bleeding. Due to additionalrisk factors for thromboembolism, 100 mg aspirin was addedto the therapy.A high bioavailability, long elimination half life, very lowintra- and intersubject variability and lack of relevant druginteractions suggest good efficacy and safety during long-termtreatment [2–4]. This was confirmed in a phase III trial in thetreatment of superficial vein thrombosis with fondaparinux2.5 mg for 45 days [5] and in one prospective observationalstudy reported on patients treated with a therapeutic dose offondaparinux (7.5 mg) for 90 days because of deep veinthrombosis or pulmonary embolism [6]. Our report describedabove is by far the longest reported therapy with fondaparinux(more than 30 months up to now).Two different models, an in vitro experiment and ex vivorabbit model with artificial mechanical heart valves,showed comparable thrombosis rates as seen with UFH orLMWH [7, 8]. To the best of our knowledge, the patientdescribed above is the first case report of successful long-term anticoagulation with fondaparinux in a patient withmechanical heart valve.M. Nagler :W. A. Wuillemin (*)Division of Haematology and Central Haematology Laboratory,Luzerner Kantonsspital,CH-6000 Lucerne 16, Switzerlande-mail: walter.wuillemin@ksl.chM. HaslauerGlaxoSmithKline AG,CH-3053 Münchenbuchsee, SwitzerlandW. A. WuilleminUniversity of Berne,CH-3000 Berne, SwitzerlandAnn Hematol (2011) 90:1225–1226DOI 10.1007/s00277-010-1143-6In conclusion, our case report confirms available dataand shows that it is possible to conduct long-term anti-coagulation with fondaparinux in combination with aspirinin a patient with a mechanical heart valve and obesity.Financial support None.Conflict of interest Dr. Wuillemin reports receiving lecture honorariaand consulting fees from Bayer, GlaxoSmithKline, Pfizer and Sanofi-Aventis. Dr. Haslauer is an employee of GlaxoSmithKline. There is noother potential conflict of interest relevant to this article.References1. Bestmann L, Zuger M, Oldenburg J, Buhler D, Maly FE (2001)Coagulation factor IX propeptide mutations causing coumarin hyper-sensitivity: identification of female alanine-10 valine heterozygotes.Thromb Haemost 85(3):567–5682. Donat F, Duret JP, Santoni A, Cariou R, Necciari J, Magnani H, deGreef R (2002) The pharmacokinetics of fondaparinux sodium inhealthy volunteers. Clin Pharmacokinet 41(Suppl 2):1–93. Mant T, Fournie P, Ollier C, Donat F, Necciari J (2002) Absence ofinteraction of fondaparinux sodium with digoxin in healthyvolunteers. Clin Pharmacokinet 41(Suppl 2):39–454. Ollier C, Faaij RA, Santoni A, Duvauchelle T, van Haard PM,Schoemaker RC, Cohen AF, de Greef R, Burggraaf J (2002)Absence of interaction of fondaparinux sodium with aspirin andpiroxicam in healthy male volunteers. Clin Pharmacokinet 41(Suppl 2):31–375. DecoususH, Prandoni P,Mismetti P, Bauersachs RM, Boda Z, BrennerB, Laporte S, Matyas L, Middeldorp S, Sokurenko G, Leizorovicz A(2010) Fondaparinux for the treatment of superficial-vein thrombosisin the legs. N Engl J Med 363(13):1222–12326. Shetty R, Seddighzadeh A, Parasuraman S, Vallurupalli NG,Gerhard-Herman M, Goldhaber SZ (2007) Once-daily fondaparinuxmonotherapy without warfarin for long-term treatment of venousthromboembolism. Thromb Haemost 98(6):1384–13867. Schlitt A, Buerke M, Hauroeder B, Peetz D, Hundt F, Bickel C,Schaefer I, Meyer J, Rupprecht HJ (2003) Fondaparinux andenoxaparin in comparison to unfractionated heparin in preventingthrombus formation on mechanical heart valves in an ex vivo rabbitmodel. Thromb Haemost 90(2):245–2518. Schlitt A, Hamilton K, Maegdefessel L, Dahm M, Theis C, EichlerM, Brockmann O, Steinseifer U, Hauroeder B, Hitzler WE,Rupprecht HJ (2006) Comparison of fondaparinux, lowmolecular-weight heparin and unfractionated heparin in preventingthrombus formation on mechanical heart valves: results of an in-vitrostudy. J Heart Valve Dis 15(6):809–8141226 Ann Hematol (2011) 90:1225–1226

Long-term anticoagulation with fondaparinux in a patient with a mechanical heart valve

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Long-term anticoagulation with fondaparinux in a patient with a mechanical heart valve

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