Fondaparinux: Does it cause HIT? can it treat HIT?

Expert Review of Hematology

Volumn 3, Issue 5, 2010, Pages 567-581

  Warkentin, Theodore E ^a,b  

^a MCMASTER UNIVERSITY   (Canada)

^b HAMILTON REGIONAL LABORATORY MEDICINE PROGRAM   (Canada)

Author keywords

antithrombotic agents; fondaparinux; heparin; heparinoid; low molecular weight heparin; thrombocytopenia; unfractionated heparin

Indexed keywords

ACENOCOUMAROL; AMPICILLIN; ARGATROBAN; DALTEPARIN; DANAPAROID; ENOXAPARIN; FIBRINOGEN; FONDAPARINUX; HEPARIN; HIRUDIN; HIRULOG; LEPIRUDIN; LOW MOLECULAR WEIGHT HEPARIN; PHENPROCOUMON; POLYANION; PROTAMINE SULFATE; PROTEIN C; THROMBOCYTE FACTOR 4; WARFARIN;

ACUTE CORONARY SYNDROME; ADRENAL NECROSIS; ANTIBODY TITER; BLEEDING; CREATININE CLEARANCE; CROSS REACTION; DEEP VEIN THROMBOSIS; DISSEMINATED INTRAVASCULAR CLOTTING; DRUG DOSE REDUCTION; DRUG WITHDRAWAL; ENZYME IMMUNOASSAY; FIBRINOGEN BLOOD LEVEL; HEART INFARCTION; HEMODILUTION; HEMOLYTIC ANEMIA; HEPARIN INDUCED THROMBOCYTOPENIA; HUMAN; IMMUNOGENICITY; INTERNATIONAL NORMALIZED RATIO; KIDNEY FAILURE; LUNG EMBOLISM; PRIORITY JOURNAL; REVIEW; SINGLE DRUG DOSE; SKIN NECROSIS; STROKE; THROMBOCYTE ACTIVATION; THROMBOCYTE COUNT; THROMBOSIS;

ADOLESCENT; ADULT; AGED; ANTIBODIES; ANTICOAGULANTS; ANTIGEN-ANTIBODY COMPLEX; DRUG ADMINISTRATION SCHEDULE; DRUG DOSAGE CALCULATIONS; FEMALE; HEPARIN; HUMANS; MALE; MIDDLE AGED; PLATELET FACTOR 4; POLYSACCHARIDES; RISK; THROMBOCYTOPENIA;

EID: 78049443734     PISSN: 17474086     EISSN: None     Source Type: Journal    
DOI: 10.1586/ehm.10.54     Document Type: Review

References (93)

1. Amiral J, Bridey F, Dreyfus M et al. Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia. Thromb. Haemost. 68(1), 95-96 (1992).
2. Arepally GM, Ortel TL. Clinical practice. Heparin-induced thrombocytopenia. N. Engl. J. Med. 355(8), 809-817 (2006).
3. 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 133(6 Suppl.), S340-S380 (2008). (Pubitemid 351892970)
4. Greinacher A, Gopinadhan M, Guenther JU et al. Close approximation of two platelet factor 4 tetramers by charge neutralization forms the antigens recognized by HIT antibodies. Arterioscler. Thromb. Vasc. Biol. 26(10), 2386-2393 (2006). (Pubitemid 44465738)
5. Greinacher A, Alban S, Omer-Adam MA, Weitschies W, Warkentin TE. Heparin-induced thrombocytopenia: a stoichiometry-based model to explain the differing immunogenicities of unfractionated heparin, low-molecular-weight heparin, and fondaparinux in different clinical settings. Thromb. Res. 122(2), 211-220 (2008).
6. Rauova L, Poncz M, McKenzie SE et al. Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia. Blood 105(1), 131-138 (2005). (Pubitemid 40053074)
7. Warkentin TE, Levine MN, Hirsh J et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N. Engl. J. Med. 332(20), 1330-1335 (1995).
8. Warkentin TE, Roberts RS, Hirsh J, Kelton JG. An improved defnition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients. Arch. Intern. Med. 163(20), 2518-2524 (2003). (Pubitemid 37385796)
9. Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin prophylaxis: a meta-analysis. Blood 106(8), 2710-2715 (2005). (Pubitemid 41510744)
10. Warkentin TE, Sheppard JI, Sigouin CS, Kohlmann T, Eichler P, Greinacher A. Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood 108(9), 2937-2941 (2006).
11. Turpie AG. Fondaparinux: a factor Xa inhibitor for antithrombotic therapy. Expert Opin. Pharmacother. 5(6), 1373-1384 (2004).
12. Alban S, Greinacher A. Role of sulphated polysaccharides in the pathogenesis of heparin-induced thrombocytopenia. In: Heparin-Induced Thrombocytopenia (4th Edition). Warkentin TE, Greinacher A (Eds). Informa Healthcare USA, NY, USA 167-186 (2007).
13. Amiral J, Lormeau JC, Marfaing-Koka A et al. Absence of cross-reactivity of SR90107A/ORG31540 pentasaccharide with antibodies to heparin-PF4 complexes developed in heparin-induced thrombocytopenia. Blood Coagul. Fibrinolysis 8(2), 114-117 (1997). (Pubitemid 27211724)
14. Warkentin TE, Cook RJ, Marder VJ et al. Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin. Blood 106(12), 3791-3796 (2005).
15. Elalamy I, Lecrubier C, Potevin F et al. Absence of in vitro cross-reaction of pentasaccharide with the plasma heparin-dependent factor of twenty-fve patients with heparin-associated thrombocytopenia. Thromb. Haemost. 74(5), 1384-1385 (1995).
16. Savi P, Chong BH, Greinacher A et al. Effect of fondaparinux on platelet activation in the presence of heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin. Blood 105(1), 139-144 (2005). (Pubitemid 40053075)
17. Warkentin TE, Cook RJ, Marder VJ, Greinacher A. Anti-PF4/heparin antibody formation post-orthopedic surgery thromboprophylaxis: the role of non-drug risk factors and evidence for a stoichiometry-based model of immunization. J. Thromb. Haemost. 8(3), 504-512 (2010).
18. Pouplard C, Couvret C, Regina S, Gruel Y. Development of antibodies specifc to polyanion-modifed platelet factor 4 during treatment with fondaparinux. J. Thromb. Haemost. 3(12), 2813-2815 (2005). (Pubitemid 41819814)
19. Kelton JG, Warkentin TE. Heparin-induced thrombocytopenia: a historical perspective. Blood 112(7), 2607-2616 (2008).
20. Warkentin TE, Kelton JG. Delayed-onset heparin-induced thrombocytopenia and thrombosis. Ann. Intern. Med. 135(7), 502-506 (2001).
21. Prechel MM, McDonald MK, Jeske WP, Messmore HL, Walenga JM. Activation of platelets by heparin-induced thrombocytopenia antibodies in the serotonin release assay is not dependent on the presence of heparin. J. Thromb. Haemost. 3(10), 2168-2175 (2005).
22. Socher I, Kroll H, Jorks S, Santoso S, Sachs UJ. Heparin-independent activation of platelets by heparin-induced thrombocytopenia antibodies: a common occurrence. J. Thromb. Haemost. 6(1), 197-200 (2008).
23. Rice L, Attisha WK, Drexler A, Francis JL. Delayed-onset heparin-induced thrombocytopenia. Ann. Intern. Med. 136(3), 210-215 (2002). (Pubitemid 34118121)
24. Warkentin TE, Bernstein RA. Delayed-onset heparin-induced thrombocytopenia and cerebral thrombosis after a single administration of unfractionated heparin. N. Engl. J. Med. 348(11), 1067-1069 (2003).
25. Alsaleh KA, Al-Nasser SM, Bates SM, Patel A, Warkentin TE, Arnold DM. Delayed-onset heparin-induced thrombocytopenia caused by low-molecular-weight heparin manifesting during fondaparinux prophylaxis. Am. J. Hematol. 83(11), 876-878 (2008).
26. Warkentin TE, Maurer BT, Aster RH. Heparin-induced thrombocytopenia associated with fondaparinux. N. Engl J. Med. 356(25), 2653-2654 (2007).
27. Rota E, Bazzan M, Fantino G. Fondaparinux-related thrombocytopenia in a previous low-molecular-weight heparin (LMWH)-induced heparin-induced thrombocytopenia (HIT). Thromb. Haemost. 99(4), 779-781 (2008). (Pubitemid 351694236)
28. Salem M, Elrefai S, Shrit MA, Warkentin TE. Fondaparinux thromboprophylaxis-associated heparin-induced thrombocytopenia (HIT) syndrome complicated by arterial thrombotic stroke. Thromb. Haemost. DOI: 10.1160/TH10-05-0284 (2010) (Epub ahead of print).
29. Warkentin TE, Lim W Can heparin-induced thrombocytopenia be associated with fondaparinux use? Reply to a rebuttal. J. Thromb. Haemost. 6(7), 1243-1246 (2008). (Pubitemid 351859141)
30. Ratuapli SK, Bobba B, Zafar H. Heparin-induced thrombocytopenia in a patient treated with fondaparinux. Clin. Adv. Hematol. Oncol. 8(1), 61-62 (2010).
31. Chong BH, Chong JJH. Review: heparin-induced thrombocytopenia associated with fondaparinux. Clin. Adv. Hematol. Oncol 8(1), 63-65.
32. Elalamy I, Tribout B. Can heparin-induced thrombocytopenia be associated with fondaparinux use? A rebuttal. J. Thromb Haemost. 6(7), 1242-1243 (2008). (Pubitemid 351859140)
33. Schindewolf M, Lindhoff-Last E. Fondaparinux-related thrombocytopenia in a patient with former HIT. Reponse to Rota et al. (Thromb. Haemost. 99, 779-781 [2008]). Thromb. Haemost. 100(1), 168-169 (2008). (Pubitemid 351948766)
34. Jay RM, Warkentin TE. Fatal heparin-induced thrombocytopenia (HIT) during warfarin thromboprophylaxis following orthopedic surgery: another example of spontaneous' HIT? J. Thromb. Haemost. 6(9), 1598-1600 (2008).
35. Pruthi RK, Daniels PR, Nambudiri GS, Warkentin TE. Heparin-induced thrombocytopenia (HIT) during postoperative warfarin thromboprophylaxis: a second example of postorthopedic surgery spontaneous' HIT? J. Thromb. Haemost. 7(3), 499-501 (2009).
36. DeSancho MT, Carlson KS, Mallik A. A case of spontaneous heparin induced thrombocytopenia and thrombosis. J. Thromb. Haemost. PP-WE-718 (2009) (Abstract).
37. Warkentin TE, Makris M, Jay RM, Kelton JG. A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia. Am. J. Med. 121(7), 632-636 (2008). (Pubitemid 351876183)
38. Gruel Y, Pouplard C, Nguyen P et al French Heparin-Induced Thrombocytopenia Study Group. Biological and clinical features of low-molecular-weight heparin-induced thrombocytopenia. Br. J. Haematol. 121(5), 786-792 (2003).
39. Warkentin TE. Agents for the treatment of heparin-induced thrombocytopenia. Hematol. Oncol. Clin. North Am. 24(4), 755-775 (2010).
40. Kuo KHM, Kovacs MJ. Successful treatment of heparin induced thrombocytopenia (HIT) with fondaparinux. Thromb. Haemost. 93(5), 999-1000 (2005).
41. Lobo B, Finch C, Howard A, Minhas S. Fondaparinux for the treatment of patients with acute heparin-induced thrombocytopenia. Thromb. Haemost. 99(1), 208-214 (2008).
42. Grouzi E, Kyriakou E, Panagou I, Spiliotopoulou I. Fondaparinux for the treatment of acute heparin-induced thrombocytopenia: a single-center experience. Clin. Appl. Thromb. Hemost. DOI: 10.1177/1076029609347900 (2009) (Epub ahead of print).
43. Pappalardo F, Scandroglio A, Maj G, Zangrillo A, D'Angelo A. Treatment of heparin-induced thrombocytopenia after cardiac surgery: preliminary experience with fondaparinux. J. Thorac. Cardiovasc. Surg. 139(3), 790-792 (2010).
44. Selleng S, Malowsky B, Strobel U et al. Early-onset and persisting thrombocytopenia in post-cardiac surgery patients is rarely due to heparin-induced thrombocytopenia even when antibody tests are positive. J. Thromb. Haemost. 8(1), 30-36 (2010).
45. Arixtra®, prescribing information. Glaxo Smith Kline, NC, USA (2010).
46. Baroletti S, Labreche M, Niles M, Fanikos J, Goldhaber SZ. Prescription of fondaparinux in hospitalised patients. Thromb. Haemost. 101(6), 1091-1094 (2009).
47. D'Angelo A, Valle PD, Fattorini A, Crippa L. Disappearance of anti-PF4/heparin antibodies under prolonged fondaparinux administration in a patient with DVT associated with LMWH-induced thrombocytopenia. Thromb. Haemost. 95(3), 573-575 (2006).
48. Filis K, Lagoudianakis EE, Pappas A et al. Heparin-induced thrombocytopenia and phlegmasia cerulean dolens of the upper limb: successfully treated with fondaparinux. Acta Haematol. 120(3), 190-191 (2008).
49. Serasli E, Antoniadou M, Tsara V et al. Successful management of acute thromboembolic disease complicated with heparin induced thrombocytopenia Type II (HIT II): a case series. Thromb. J. 6, 9 (2008). (Pubitemid 352044781)
50. Spyropoulos AC, Magnuson S, Koh SK. The use of fondaparinux for the treatment of venous thromboembolism in a patient with heparin-induced thrombocytopenia and thrombosis caused by heparin fushes. Ther. Clin. Risk Manag. 4(3), 653-657 (2008). (Pubitemid 352037908)
51. Thorsteinsson GS, Magnussson M, Hallberg LM et al. Cerebral venous thrombosis and heparin-induced thrombocytopenia in an 18-year old male with severe ulcerative colitis. World J. Gastroenterol. 14(28), 4576-4579 (2008).
52. Neykova A, Tzvetkov B, Merah AK, Matheron C, Kirsch M. The HIT treatment in a cardiac surgery patient. Int. J. Cardiol. DOI: 10.1016/j. ijcard.2009.03.027 (2009) (Epub ahead of print).
53. ®), as an alternative antithrombotic prophylaxis when there is hypersensitivity to low molecular weight and unfractionated heparins. Haematologica 88(11), ECR32 (2003).
54. Sideris SK, Bonios MJ, Eftihiadis EE et al. Severe thrombocytopenia after heparin therapy in a patient with unstable angina and recent stent implantation. Hellenic J. Cardiol. 46(3), 242-246 (2005).
55. Jankowski K, Ozdzenska-Milke E, Lichodziejewska B, Huba M, Ciurzynski M, Pruszczyk P. [Recurrent pulmonary embolism in a patient with heparin-induced thrombocytopenia]. Pol. Arch. Med. Wewn. 117 (11-12), 524-526 (2007). (Pubitemid 351169854)
56. Nowicka A, Kandziora M, Szymanowska K et al. [Heparin-induced thrombocytopenia in a patient with massive pulmonary embolism and dilated cardiomyopathy, successfully treated with fondaparinux-a case report]. Kardiol. Pol. 66(12), 1306-1308 (2008).
57. Akoum R, Mahfoud D, Ghaoui A et al. Budd-Chiari syndrome and heparin-induced thrombocytopenia in polycythemia vera: successful treatment with repeated TIPS and interferon a. J. Cancer Res. Ther. 5(4), 305-308 (2009).
58. Seldrum S, Lambert M, Hainaut P. Heparin-induced thrombocytopenia successfully treated with fondaparinux. Acta Clin. Belg. 64(2), 144-146 (2009).
59. Lapecorella M, Lucchesi A, Di Ianni M et al. Unusual onset of venous thromboembolism and heparin-induced thrombocytopenia in a patient with essential thrombocythemia. Blood Coagul. Fibrinolysis 21(1), 85-90 (2010).
60. ® in a patient with paroxysmal nocturnal hemoglobinuria, Budd-Chiari syndrome and heparin-induced thrombocytopenia. J. Thromb. Haemost. 1(11), 2452-2453 (2003).
61. ®) in a dialysis patient with symptomatic heparin-induced thrombocytopenia type II. Nephrol. Dial. Transplant. 20(2), 444-446 (2005). (Pubitemid 40276907)
62. Holtan SG, Knox SK, Tefferi A. Use of fondaparinux in a patient with antiphospholipid antibody syndrome and heparin-associated thrombocytopenia. J. Thromb. Haemost. 4(7), 1632-1634 (2006). (Pubitemid 43919199)
63. Gralec R, Dybowska M, Kuca P, Burakowski J, Tomkowski W. [Thrombocytopenia probably heparin-induced in woman with tumor of the heart and pulmonary embolism]. Pneumonol. Alergol. Pol. 74(2), 216-220 (2006). (Pubitemid 44504026)
64. Myzienski AE, Lutz MF, Smythe MA. Unfractionated heparin dosing for venous thromboembolism in morbidly obese patients: case report and review of the literature. Pharmacotherapy 30(3), e105-e112 (2010).
65. Warkentin TE, Kelton JG. Temporal aspects of heparin-induced thrombocytopenia. N. Engl. J. Med. 344(17), 1286-1292 (2001).
66. Greinacher A, Kohlmann T, Strobel U, Sheppard JI, Warkentin TE. The temporal profle of the anti-PF4/heparin immune response. Blood 113(20), 4970-4976 (2009).
67. Patterson SL, LaMonte MP, Mikdashi JA, Haines ST, Hursting MJ. Anticoagulation strategies for treatment of ischemic stroke and antiphospholipid syndrome: case report and review of the literature. Pharmacotherapy 26(10), 1518-1525 (2006). (Pubitemid 44521737)
68. Ekbatani A, Asaro LR, Malinow AM. Anticoagulation with argatroban in a parturient with heparin-induced thrombocytopenia. Int. J. Obstet. Anesth. 19(1), 82-87 (2010).
69. Maurer SH, Wilimas JA, Wang WC, Reiss UM. Heparin induced thrombocytopenia and re-thrombosis associated with warfarin and fondaparinux in a child. Pediatr. Blood Cancer 53(3), 468-471 (2009).
70. Turpie AG, Bauer KA, Eriksson BI, Lassen MR. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch. Intern. Med. 162(16), 1833-1840 (2002).
71. Turpie AG, Bauer KA, Caprini JA, Comp PC, Gent M, Muntz JE; Apollo Investigators. Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery: a randomized, double-blind comparison. J. Thromb. Haemost. 5(9), 1854-1861 (2007). (Pubitemid 47288942)
72. Kanaan AO, Silva MA, Donovan JL, Roy T, Al-Homsi AS. Meta-analysis of venous thromboembolism prophylaxis in medically ill patients. Clin. Ther. 29(11), 2395-2405 (2007).
73. Cohen AT, Davidson BL, Gallus AS et al; ARTEMIS Investigators. Effcacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. Br. Med. J. 332(7537), 325-329 (2006)
74. Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators, Yusuf S, Mehta SR, Chrolavicius S et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N. Engl. J. Med. 354(14), 1464-1476 (2006). (Pubitemid 44268228)
75. Yusuf S, Mehta SR, Chrolavicius S et al; OASIS-6 TRIAL Group. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA 295(13), 1519-1530 (2006).
76. Büller HR, Davidson BL, Decousus H et al; Matisse investigators. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis. A randomized trial. Ann. Intern. Med. 140(11), 867-873 (2004). (Pubitemid 38685267)
77. Büller H, Davidson BL, Decousus H et al.; Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N. Engl. J. Med. 349(18), 1695-1702 (2003). (Pubitemid 37315006)
78. Harenberg J, Jörg I, Fenyvesi T. Treatment of heparin-induced thrombocytopenia with fondaparinux. Haematologica 89(8), 1017-1018 (2004). (Pubitemid 39049916)
79. Warkentin TE, Sheppard JI. Testing for heparin-induced thrombocytopenia antibodies. Transfus. Med. Rev. 20(4), 259-272 (2006).
80. Greinacher A, Juhl D, Strobel U et al. Heparin-induced thrombocytopenia: a prospective study on the incidence, platelet-activating capacity and clinical signifcance of anti-PF4/heparin antibodies of the IgG, IgM, and IgA classes. J. Thromb. Haemost. 5(8), 1666-1673 (2007). (Pubitemid 47091409)
81. Bakchoul T, Giptner A, Najaoui A, Bein G, Santoso S, Sachs UJ. Prospective evaluation of PF4/heparin immunoassays for the diagnosis of heparin-induced thrombocytopenia. J. Thromb. Haemost. 9(8), 1260-1265 (2009).
82. Lo GK, Sigouin CS, Warkentin TE. What is the potential for overdiagnosis of heparin-induced thrombocytopenia? Am. J. Hematol. 82(12), 1037-1043 (2007).
83. Wester JPJ, Leyte A, Oudemans-van Straaten HM et al. Low-dose fondaparinux in suspected heparin-induced thrombocytopenia in the critically ill. Neth. J. Med. 65(3), 101-108 (2007). (Pubitemid 46487887)
84. Farner B, Eichler P, Kroll H, Greinacher A. A comparison of danaparoid and lepirudin in heparin-induced thrombocytopenia. Thromb. Haemost. 85(6), 950-957 (2001). (Pubitemid 32573742)
85. Donat F, Duret JP, Santoni A et al. The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clin. Pharmacokinet. 41(Suppl. 2), 1-9 (2002). (Pubitemid 35155551)
86. Sombolos KI, Fragia TK, Gionanlis LC et al. Use of fondaparinux as an anticoagulant during hemodialysis: a preliminary study. Int. J. Clin. Pharmacol. Ther. 46(4), 198-203 (2008). (Pubitemid 351493991)
87. Mehta SR, Granger CB, Eikelboom JW et al. Effcacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial. J. Am. Coll. Cardiol. 50(18), 1742-1751 (2007).
88. Turpie AG, Lensing AW, Fuji T, Boyle DA. Pharmacokinetic and clinical data supporting the use of fondaparinux 1.5 mg once daily in the prevention of venous thromboembolism in renally impaired patients. Blood Coagul. Fibrinolysis 20(2), 114-121 (2009).
89. Greinacher A, Warkentin TE. The direct thrombin inhibitor hirudin. Thromb. Haemost. 99(5), 819-829 (2008). (Pubitemid 351705298)
90. Chong BH, Gallus AS, Cade FJ et al; Australian HIT Study Group. Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopenia with thrombosis: a clinical outcome study. Thromb. Haemost. 86(5), 1170-1175 (2001).
91. Fugate S, Chiappe J. Standardizing the management of heparin-induced thrombocytopenia. Am. J. Health Syst. Pharm. 65(4), 334-339 (2008). (Pubitemid 351294843)
92. McIntyre KM, Warkentin TE. Legal aspects of heparin-induced thrombocytopenia. In: Heparin-Induced Thrombocytopenia (3rd Edition). Warkentin TE, Greinacher A (Eds). Marcel Dekker, NY, USA 573-585 (2004).
93. US FDA Drug Bulletin 12, 4-5 (1982).