A retrospective evaluation of fondaparinux for confirmed or suspected heparin-induced thrombocytopenia in left-ventricular-assist device patients

Journal of Cardiothoracic Surgery

Toby Thomas¹  Aesha Shah¹  Suhuir Dajani¹  Nicholas Tillman¹  Scott T Benken² 

[1] Department of Clinical Sciences, Roosevelt University College of Pharmacy, Schaumburg, IL, USA;Department of Pharmacy, The University of Chicago Medicine, 5841 S. Maryland Ave. TE026, MC0010, Chicago, IL 60637, USA

关键词: Anticoagulation;    Fondaparinux;    Bleeding;    Thrombosis;    Heparin-induced thrombocytopenia;    Left-ventricular-assist device;   

Others  :  811117
DOI  :  10.1186/1749-8090-9-55

 received in 2013-10-18, accepted in 2014-03-17,  发布年份 2014

【 摘 要 】

Background

Thrombotic events are a common complication of left ventricular assist device placement and warrant prophylactic anticoagulation. Heparin is the most common anticoagulant used for prophylaxis of thrombotic events in left ventricular assist device patients as a transition to oral anticoagulants but carries the risk of heparin-induced thrombocytopenia. Limited data is available for the treatment of heparin-induced thrombocytopenia in this patient population. We report an evaluation of 8 left ventricular assist device patients with suspected or confirmed HIT started on fondaparinux at the time of heparin-induced platelet-factor-4 antibody positivity.

Methods

Adult patients were reported if they were heparin-induced platelet antibody positive, tested via enzyme-linked immunusorbent assay, post-operative after left-ventricular assist device, and were initiated on fondaparinux at the time of heparin-induced platelet antibody positivity. Waiver of informed consent was granted from the institutional review board. Baseline demographics, clinical course of HIT, safety and efficacy variables were collected.

Results

Eight patients receiving fondaparinux were identified and included in this report. The patient group was on average 49 years old, weighing 95 kg, with calculated BMI 28.8 and consisted primarily of Caucasian males. Three patients developed new thromboses after initiation of fondaparinux for heparin-induced thrombocytopenia. Only one patient had a major bleeding event of an overt bleed after initiation of fondaparinux therapy.

Conclusions

Given the lack of major bleeding in this evaluation, fondaparinux could be a potentially safe treatment option for left ventricular assist device patients that are heparin-induced platelet antibody positive pending confirmatory testing results. Given the development of new thromboses in 3 of 8 patients, concern exists about the efficacy of fondaparinux in this patient population. Significant limitations exist regarding these conclusions in this evaluation. Controlled, systematic evaluations are necessary to delineate safety and efficacy of fondaparinux for heparin-induced thrombocytopenia in this population.

【 授权许可】

   
2014 Benken et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Friedrich EB, Bohm M: Management of end stage heart failure. Heart 2007, 93(5):626-631.
• [2]Miller LW: Is left ventricular assist device therapy underutilized in the treatment of heart failure? Circulation 2011, 123:1552-1558.
• [3]Cleveland JC Jr, Naftel DC, Reece TB, Murray M, Antaki J, Pagani FD, Kirklin JK: Survival after biventricular assist device implantation: analysis of interagency registry for mechanically assisted circulatory support database. J Heart Lung Transplant 2011, 30:862-869.
• [4]Wu L, Weng YG, Dong NG, Krabatsch T, Stepanenko A, Hennig E, Hetzer R: Outcomes of the HeartWare ventricular assist system support in 141 patients: a single-centre experience. Euro J of CT Surg 2013, 44:139-145.
• [5]Dell’Aquila AM, Schneider SR, Schlarb D, Redwan B, Sindermann JR, Ellger B, Stypmann J, Tjan TD, Scheld HH, Hoffmeier A: Initial clinical experience with the HeartWare left ventricular assist system: a single-center report. Ann Thorac Surg 2013, 95(1):170-177.
• [6]Park SJ, Milano CA, Tatooles AJ, Rogers JG, Adamson RM, Steidley DE, Ewald GA, Sundareswaran KS, Farrar DJ, Slaughter MS, HeartMate II Clinical Investigators: Outcomes in advanced heart failure patients with left ventricular assist devices for destination therapy. Circ Heart Fail 2012, 5(2):241-248.
• [7]Barnes K: Complications in patients with ventricular assist devices. Dimens Crit Care Nurs 2008, 27(6):233-241.
• [8]Kroekel PA, George L, Eltoukhy N: How to manage the patient in the emergency department with a left ventricular assist device. J Emerg Nursing 2012, 1(7):1010-1016.
• [9]Schaffer JM, Arnaoutakis GJ, Allen JG, Weiss ES, Patel ND, Russell SD, Shah AS, Conte JV: Bleeding complications and blood product utilization with left ventricular assist device implantation. Ann Thorac Surg 2011, 91(3):740-747.
• [10]Mehra MR, Griffith BP: Assisted circulation in the treatment of heart failure: Bonow: Braunwald’s heart disease - a textbook of cardiovascular medicine. 9th edition. Philadelphia, PA: El Sevier Inc; 2012:617-626.
• [11]Kurlen S, Hughes KA: Anticoagulation and bleeding in patients with ventricular assist devices walking the tightrope. AACN Adv Crit Care 2012, 23(1):91.
• [12]Feldman D, Pamboukian SV, Teutuberg JJ, Birks E, Lietz K, Moore SA, Morgan JA, Arabia F, Bauman ME, Buchholz HW, Deng M, Dickstein ML, El-Banayosy A, Elliot T, Goldstein DJ, Grady KL, Jones K, Hryniewicz K, John R, Kaan A, Kusne S, Loebe M, Massicotte MP, Moazami N, Mohacsi P, Mooney M, Nelson T, Pagani F, Perry W, Potapov EV, Eduardo Rame J, et al.: The 2013 international society for heart and lung transplantation guidelines for mechanical circulatory support: executive summary. J of Heart and Lung Transplant 2013, 32:157-187.
• [13]Warkentin TE, Greinacher A, Koster A: Heparin induced thrombocytopenia in patients with VAD; are new prevention strategies required? Ann Thorac Surg 2009, 87(5):1633-1640.
• [14]Warkentin TE, Greinacher A, Koster A, Lincoff AM: Treatment and prevention of heparin induced thrombocytopenia: American college of chest physicians evidence-based clinical practice guidelines (8th edition). Chest 2008, 133(6 Suppl):340S-380S.
• [15]Pappalardo F, Scandroglio AM, Potapov E, Stepanenko A, Maj G, Krabatsch T, Zangrillo A, Koster A, Hetzer R: Argatroban anticoagulation for heparin induced thrombocytopenia in patients with ventricular assist devices. Minerva Anestesiol 2012, 78(3):330-335.
• [16]Czosnowski QA, Finks SW, Rogers KC: Bivalirudin for patients with heparin-induced thrombocytopenia undergoing cardiovascular surgery. Ann Pharmacother 2008, 42(9):1304-1309.
• [17]Koster A, Weng Y, Böttcher W, Gromann T, Kuppe H, Hetzer R: Successful use of bivalirudin as anticoagulant for ECMO in patient with acute HIT. Ann Thorac Surg 2007, 83:1865-1867.
• [18]Rutledge JM, Chakravarti S, Massicotte MP, Buchholz H, Ross DB, Joashi U: Antithrombotic strategies in children receiving long-term Berlin heart EXCOR ventricular assist device therapy. J Heart Lung Transplant 2013, 32(5):569-573.
• [19]Warkentin TE, Pai M, Sheppard JI, Schulman S, Spyropoulos AC, Eikelboom JW: Fondaparinux treatment of acute heparin induced thrombocytopenia confirmed by the serotonin-releaseassay: a 30-month, 16-patient case series. J Thromb Haemost 2011, 9(12):2389-2396.
• [20]Corbett TL, Elher KS, Garwood CL: Successful use of fondaparinux in a patient with a mechanical heart valve replacement and a history of heparin-induced thrombocytopenia. J Thromb Thrombolysis 2010, 30(3):375-377.
• [21]Gellatly RM, Leet A, Brown KE: Fondaparinux: an effective bridging strategy in heparin-induced thrombocytopenia and mechanical circulatory support. J Heart Lung Transplant 2013. S1053-2498(13)01355-7. doi: 10.1016/j.healun.2013.07.015. [Epub ahead of print]
• [22]Information P: ARIXTRA (R) subcutaneous injection, fondaparinux sodium subcutaneous injection. Research Triangle Park, NC: GlaxoSmithKline; 2008.
• [23]Cuker A, Cines DB: How I treat heparin-induced thrombocytopenia. Blood 2012, 119(10):2209-2218.
• [24]Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A: Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 2006, 4:759-765.
• [25]Moulton MJ, Creswell LL, Mackey ME, Cox JL, Rosenbloom M: Re-exploration for bleeding is a risk factor for adverse outcome after cardiac operations. J Thoracic Cardiovasc Surg 1996, 110:1037-1046.
• [26]Paparella D, Brister SJ, Buchanan MR: Coagulation disorders of cardiopulmonary bypass: a review. Intensive Care Med 2004, 30(10):1873-1881.
• [27]Crow S, Chen D, Milano C, Thomas W, Joyce L, Piacentino V 3rd: Acquired von Willebrand syndrome in continuous-flow ventricular assist device recipients. Ann Thorac Surg 2010, 90:1263-1269.
• [28]Greinacher A, Janssens U, Berg G, Böck M, Kwasny H, Kemkes-Matthes B, Eichler P, Völpel H, Pötzsch B, Luz M: Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Circulation 1999, 100:587-593.
• [29]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, 96:846-851.
• [30]Eichler P, Lubenow N, Greinacher A: Results of the third prospective study of treatment with lepirudin in patients with heparin-induced thrombocytopenia (HAT) [abstract]. Blood 2002, 100(1):704a.
• [31]Lubenow N, Eichler P, Greinacher A: Results of a large drug monitoring program confirms the safety and efficacy of refludan (Lepirudin) in patients with immune-mediated heparin-induced thrombocytopenia [abstract]. Blood 2002, 100(1):502a.
• [32]Lewis BE, Wallis DE, Berkowitz SD, Matthai WH, Fareed J, Walenga JM, Bartholomew J, Sham R, Lerner RG, Rustagi PK, Jang IK, Rifkin SD, Moran J, Hursting MJ, Kelton JG, ARG-911 Study Investigators: Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation 2001, 103:1838-1843.
• [33]Lewis BE, Wallis DE, Leya F, Hursting MJ, Kelton JG, Argatroban-915 Investigators: Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med 2003, 163:1849-1856.
• [34]Warkentin TE, Sheppard JI, Moore JC, Sigouin CS, Kelton JG, Sigouin CS, Kelton JG: Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays. J Thromb Haemost 2008, 6:1304-1312.
• [35]Chung JH, Gikakis N, Rao AK, Drake TA, Colman RW, Edmunds LH Jr: Pericardial blood activated the extrinsic coagulation pathway during clinical cardiopulmonary bypass. Circulation 1996, 93:2014-2018.
• [36]Starlin RC, Moazami N, Silvestry SC, Ewald G, Rogers JG, Milano CA, Rame JE, Acker MA, Blackstone EH, Ehrlinger J, Thuita L, Mountis MM, Soltesz EG, Soltesz EG, Lytle BW, Lytle BW, Smedira NG: Unexpected abrupt increase in left ventricular assist device thrombosis. NEJM 2014, 370:33-40.
• [37]Pearson MA, Nadeau C, Blais N: Correlation of optical density with clinical diagnosis of heparin-induced thrombocytopenia: a retrospective study of 104 patients with positive anti-PF4/heparin ELISA. Clin Appl Thromb Hemost 2013. Nov 27 [epub]
• [38]Selleng S, Selleng K, Wollert HG, Muellejans B, Lietz T, Warkentin TE, Greinacher A: Heparin-induced thrombocytopenia in patients requiring prolonged intensive care unit treatment after cardiopulmonary bypass. J Thromb Haemost 2008, 6(3):428-435.
• [39]Warkentin TE: How I diagnose and manage HIT. Hematology Am Soc Hematol Educ Program 2011, 2011(1):143-149.
• [40]Warkentin TE: Agents for the treatment of heparin-induced thrombocytopenia. Hematol Oncol Clin North Am 2010, 24(4):755-775.
• [41]Garcia DA, Baglin TP, Weitz JI, Samama MM, American College of Chest Physicians: Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest 2012, 141(2 Suppl):24-43.