Emre TEKGÜNDÜZ, Emre TEKGÜNDÜZ, Seval AKPINAR, Erman ÖZTÜRK, Gülsüm Emel PAMUK, Burhan TURGUT, Muzaffer DEMİR

Fondaparinuks Heparinin İndüklediği Trombositopeni Hastalarında Etkili Bir Alternatif Antikoagülan Mıdır? Olgu Sunumu ve Literatür Derlemesi

Heparine bağlı trombositopeni (HIT) nadir olmasına karşın heparin tedavisinin en çok korkulan komplikasyonlarından biridir. Heparine bağlı trombositopeni heparin ile temas sonrası oluşan, antikor aracılı edinsel ve geçici bir trombotik bozukluktur. Fraksiyone olmayan heparin hemodiyaliz sırasında kullanılan standart antikoagülandır ve heparin ile sürekli temas eden hemodiyaliz hastalarında HIT riski artmıştır. Burada kronik zeminde akut böbrek yetersizliği olan ve hemodiyaliz sonrasında HIT gelişen 75 yaşında bir erkek hastayı bildiriyoruz. Hastada derin ven trombozu saptandı ve fondaparinuks ile başarıyla tedavi edildi. Bu yazımızda ayrıca HIT hastalarında gelişen trombozun profilaksi ve tedavisinde fondaparinuksun endikasyon dışı kullanımını derledik. Fondaparinuks heparin ile reaksiyon veren antikorların çoğunluğunca tanınmayacak kadar küçük olduğundan lepirudin ve danaparoid gibi lisanslı ilaçların bulunmadığı durumlarda, semptomatik HIT hastaları için mantıklı bir alternatif antikoagülan olabilir.

Anahtar Kelimeler:

Heparine bağlı trombositopeni, tromboz, hemodiyaliz, fondaparinuks

Is Fondaparinux an Effective Alternative Anticoagulant in Patients With Heparin-Induced Thrombocytopenia Type II? A Case Report and Review of the Literature

Although rare, heparin-induced thrombocytopenia (HIT) is one of the most feared complications of heparin therapy. It is an antibody-mediated, acquired and transient thrombotic disorder following exposure to heparin. Unfractionated heparin is the standard anticoagulation used in hemodialysis sessions and hemodialysis patients who are continually exposed to heparin are at increased risk for HIT. We report a 75-year-old male patient with acute-on-chronic renal failure who subsequently developed HIT while on hemodialysis. The patient was presented with deep vein thrombosis and successfully treated with fondaparinux. In this report we also review the off-label use of fondaparinux for the treatment and prophylaxis of thrombosis in patients with HIT. As fondaparinux is too small to be recognized by the majority of heparin-reactive antibodies it could be a reasonable alternative anticoagulant for symptomatic HIT patients where licensed drugs like lepirudin and danaparoid are not available. Turkish Başlık: Fondaparinuks Heparinin İndüklediği Trombositopeni Hastalarında Etkili Bir Alternatif Antikoagülan Mıdır? Olgu Sunumu ve Literatür Derlemesi Anahtar Kelimeler: Heparine bağlı trombositopeni, tromboz, hemodiyaliz, fondaparinuks Heparine bağlı trombositopeni (HIT) nadir olmasına karşın heparin tedavisinin en çok korkulan komplikasyonlarından biridir. Heparine bağlı trombositopeni heparin ile temas sonrası oluşan, antikor aracılı edinsel ve geçici bir trombotik bozukluktur. Fraksiyone olmayan heparin hemodiyaliz sırasında kullanılan standart antikoagülandır ve heparin ile sürekli temas eden hemodiyaliz hastalarında HIT riski artmıştır. Burada kronik zeminde akut böbrek yetersizliği olan ve hemodiyaliz sonrasında HIT gelişen 75 yaşında bir erkek hastayı bildiriyoruz. Hastada derin ven trombozu saptandı ve fondaparinuks ile başarıyla tedavi edildi. Bu yazımızda ayrıca HIT hastalarında gelişen trombozun profilaksi ve tedavisinde fondaparinuksun endikasyon dışı kullanımını derledik. Fondaparinuks heparin ile reaksiyon veren antikorların çoğunluğunca tanınmayacak kadar küçük olduğundan lepirudin ve danaparoid gibi lisanslı ilaçların bulunmadığı durumlarda, semptomatik HIT hastaları için mantıklı bir alternatif antikoagülan olabilir.

Keywords:

Heparin-induced thrombocytopenia, thrombosis, hemodialysis, fondaparinux,

PDF

___

Warkentin TE. Think of HIT. Hematology Am Soc Hematol Educ Program 2006:408-14.
Demir M, Duran E, Yigitbasi O, Vural O, Kurum T, Yuksel M, et al. Incidence of antiheparin-platelet factor 4 antibodies and heparin-induced thrombo- cytopenia in Turkish patients undergoing cardiac surgery. Clin Appl Thromb Hemost 2007;13:279-84.
Kuo KH, Kovacs MJ. Fondaparinux: a potential new therapy for HIT. Hematology 2005;10:271-5.
Warkentin TE. Heparin-induced thrombocytopenia: a clinicopathologic syndrome. Thromb Haemost 1999;82:439-47.
Demir M, Ahmad S, Walenga JM, Fareed J. Laboratory diagnosis of heparin-induced thrombocytopenia. Turk J Haematol 2000;17(3 Suppl):181-90.
Rice L. Heparin-induced thrombocytopenia: myths and misconceptions (that will cause trouble for you and your patient). Arch Intern Med 2004;164:1961-4.
Greinacher A, Eichler P, Lubenow N, Kwasny H, Luz M. Heparin-induced thrombocytopenia with thromboembolic complications: meta-analysis of 2 prospective trials to assess the value of parenteral treatment with lepirudin and its therapeutic aPTT range. Blood 2000;96:846-51.
Hong AP, Cook DJ, Sigouin CS, Warkentin TE. Central venous catheters and upper-extremity deep- vein thrombosis complicating immune heparin- induced thrombocytopenia. Blood 2003;101:3049-51.
Keeling D, Davidson S, Watson H, Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. The management of heparin-induced thrombocytopenia. Br J Haematol 2006;133:259-69.
Greinacher A, Amiral J, Dummel V, Vissac A, Kiefel V, Mueller-Eckhardt C. Laboratory diagnosis of hep- arin-associated thrombocytopenia and comparison of platelet aggregation test, heparin-induced plate- let activation test, and platelet factor 4/heparin enzyme-linked immunosorbent assay. Transfusion 1994;34:381-5.
Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):311S-337S.
Kelton JG. The pathophysiology of heparin-induced thrombocytopenia: biological basis for treatment. Chest 2005;127(2 Suppl):9S-20S.
O'Shea SI, Ortel TL, Kovalik EC. Alternative methods of anticoagulation for dialysis-dependent patients with heparin-induced thrombocytopenia. Semin Dial 2003;16:61-7.
Greinacher A, Lubenow N, Eichler P. Anaphylactic and anaphylactoid reactions associated with lepiru- din in patients with heparin-induced thrombocy- topenia. Circulation 2003;108:2062-5.
Farner B, Eichler P, Kroll H, Greinacher A. A compar- ison of danaparoid and lepirudin in heparin-induced thrombocytopenia. Thromb Haemost 2001;85:950-7.
Lormeau JC, Herault JP. The effect of the syn- thetic pentasaccharide SR 90107/ORG 31540 on thrombin generation ex vivo is uniquely due to ATIII-mediated neutralization of factor Xa. Thromb Haemost 1995;74:1474-7.
Spinler SA. New concepts in heparin-induced throm- bocytopenia: diagnosis and management. J Thromb Thrombolysis 2006;21:17-21.
Warkentin TE, Maurer BT, Aster RH. Heparin- induced thrombocytopenia associated with fonda- parinux. N Engl J Med 2007;356:2653-5.
Savi P, Chong BH, Greinacher A, Gruel Y, Kelton JG, Warkentin TE, et al. Effect of fondaparinux on plate- let activation in the presence of heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin. Blood 2005;105:139-44.
Hirsh J, Heddle N, Kelton JG. Treatment of heparin- induced thrombocytopenia: a critical review. Arch Intern Med 2004;164:361-9.
Lobo B, Finch C, Howard A, Minhas S. Fondaparinux for the treatment of patients with acute heparin- induced thrombocytopenia. Thromb Haemost 2008;99:208-14.
Holtan SG, Knox SK, Tefferi A. Use of fondaparinux in a patient with antiphospholipid antibody syn- drome and heparin-associated thrombocytopenia. J Thromb Haemost 2006;4:1632-4.
Harenberg J, Jörg I, Fenyvesi T. Treatment of hepa- rin-induced thrombocytopenia with fondaparinux. Haematologica 2004;89:1017-8.
Harenberg J, Jörg I, Fenyvesi T, Hagedorn A, Giese C, Trager I. Prophylaxis of recurrent thromboembolism in a patient with a history of heparin-induced throm- bocytopenia with thrombosis, anti-lepirudin antibod- ies after Bjork-Shiley aortic valve implantation using fondaparinux. J Thromb Haemost 2003;(Suppl 1): Abstract P2040.
D'Amico EA, Villaça PR, Gualandro SF, Bassitt RP, Chamone DA. Successful use of Arixtra in a patient with paroxysmal nocturnal hemoglobinuria, Budd- Chiari syndrome and heparin-induced thrombocy- topenia. J Thromb Haemost 2003;1:2452-3.
Lian EC, Chua L, Oberstein E. Long-term use of fondaparinux in a patient with antiphospholipid syndrome, heparin-induced thrombocytopenia and refractoriness to coumarin. Blood 2003;102:Abstract 4206.
Bradner J, Hallisey RK, Kuter DJ. Fondaparinux in the treatment of heparin-induced thrombocytopenia. Blood 2004;104:Abstract 1775.
Kovacs MJ. Successful treatment of heparin induced thrombocytopenia (HIT) with fondaparinux. Thromb Haemost 2005;93:999-1000.
Rubin N, Rubin J. Treatment of heparin-induced thrombocytopenia with thrombosis (HITT) in preg- nancy with fondaparinux. Blood 2003;102:Abstract 4190.
Parody R, Oliver A, Souto JC, Fontcuberta J. Fondaparinux (ARIXTRA) as an alternative anti- thrombotic prophylaxis when there is hypersensi- tivity to low molecular weight and unfractionated heparins. Haematologica 2003;88:ECR32. [Abstract]
Haase M, Bellomo R, Rocktaeschel J, Ziemer S, Kiesewetter H, Morgera S, et al. Use of fondaparinux (ARIXTRA) in a dialysis patient with symptom- atic heparin-induced thrombocytopaenia type II. Nephrol Dial Transplant 2005;20:444-6.
Piovella F, Barone M, Beltrametti C, Piovella C, D’Armini AM, Marzani FC, et al. Efficacy of fonda- parinux in the treatment of heparin-induced thrombo- cytopenia with venous thromboembolism: reduction of thromboembolic burden, normalization of platelet count and disappearance of anti-platelet factor 4/ heparin antibodies. Blood 2006;108:Abstract 575.
D'Angelo A, Valle PD, Fattorini A, Luciano C. Disappearance of anti-PF4/heparin antibodies under prolonged fondaparinux administration in a patient with DVT associated with LMWH-induced thrombo- cytopenia. Thromb Haemost 2006;95:573-5.
Warkentin TE. Fondaparinux versus direct thrombin inhibitor therapy for the management of heparin- induced thrombocytopenia (HIT)--bridging the River Coumarin. Thromb Haemost 2008;99:2-3.