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Highlights & Basics
- Heparin-induced thrombocytopenia (HIT) is a severe drug reaction to heparin that can lead to life- and limb-threatening venous and/or arterial thromboembolism.
- Diagnosis requires the combination of a compatible clinical picture and laboratory confirmation of the presence of heparin-dependent platelet-activating HIT antibodies.
- The 4Ts score is commonly used to determine the clinical probability of HIT.
- Neither discontinuation of heparin alone nor initiation of a vitamin K antagonist alone (e.g., warfarin) is sufficient to stop the development of thrombosis in a patient with acute HIT.
- If a patient has suspected HIT and at least an intermediate-probability 4Ts score, all sources of heparin (including low molecular weight heparin) must be discontinued and a nonheparin anticoagulant should be initiated.
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Warkentin T, Kelton J. Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med. 2001;344:1286-1292.[Abstract][Full Text]
Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018 Nov 27;2(22):3360-92.[Abstract][Full Text]
Linkins LA, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: antithrombotic therapy and prevention of thrombosis (9th ed). American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(2 Suppl):e495S-e530S.[Abstract][Full Text]
Watson H, Davidson S, Keeling D, et al. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. Br J Haematol. 2012 Dec;159(5):528-40.[Abstract][Full Text]
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2. Warkentin TE. Fondaparinux: does it cause HIT? Can it treat HIT? Expert Rev Hematol. 2010 Oct;3(5):567-81.[Abstract]
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4. Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996 Nov;101(5):502-7.[Abstract]
5. Warkentin T, Kelton J. Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med. 2001;344:1286-1292.[Abstract][Full Text]
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24. Kelton JG, Smith JW, Warkentin TE, et al. Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4. Blood. 1994;83:3232-3239.[Abstract][Full Text]
25. Chong BH, Fawaz I, Chesterman CN, et al. Heparin-induced thrombocytopenia: mechanism of interaction of the heparin-dependent antibody with platelets. Br J Haematol. 1989;73:235-240.[Abstract]
26. Warkentin TE, Sheppard JI. Generation of platelet-derived microparticles and procoagulant activity by heparin-induced thrombocytopenia IgG/serum and other IgG platelet agonists: a comparison with standard platelet agonists. Platelets. 1999;10:319-326.[Abstract]
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33. Rauova L, Poncz M, McKenzie SE, et al. Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia. Blood. 2005 Jan 1;105(1):131-8.[Abstract][Full Text]
34. Greinacher A, Alban S, Dummel V, et al. Characterization of the structural requirements for a carbohydrate based anticoagulant with a reduced risk of inducing the immunological type of heparin-associated thrombocytopenia. Thromb Haemost. 1995 Sep;74(3):886-92.[Abstract]
35. Greinacher A, Alban S, Omer-Adam MA, et al. 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. 2008;122(2):211-20.[Abstract]
36. Lo G, Juhl D, Warkentin T, et al. Evaluation of pretest clinical score (4 T's) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006 Apr;4(4):759-65.[Abstract]
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39. Cuker A, Gimotty PA, Crowther MA, et al. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood. 2012 Nov 15;120(20):4160-7.[Abstract][Full Text]
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43. Warkentin TE. Anticoagulant failure in coagulopathic patients: PTT confounding and other pitfalls. Expert Opin Drug Saf. 2014 Jan;13(1):25-43.[Abstract]
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45. Watson H, Davidson S, Keeling D, et al. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. Br J Haematol. 2012 Dec;159(5):528-40.[Abstract][Full Text]
46. Linkins LA, Bates SM, Lee AY, et al. Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study. Blood. 2015 Jul 30;126(5):597-603.[Abstract][Full Text]
47. Nagler M, Bachmann LM, Ten Cate H, et al. Diagnostic value of immunoassays for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood. 2016 Feb 4;127(5):546-57.[Abstract][Full Text]
48. Sun L, Gimotty PA, Lakshmanan S, et al. Diagnostic accuracy of rapid immunoassays for heparin-induced thrombocytopenia. A systematic review and meta-analysis. Thromb Haemost. 2016 May 2;115(5):1044-55.[Abstract]
49. Minet V, Dogné JM, Mullier F. Functional assays in the diagnosis of heparin-induced thrombocytopenia: a review. Molecules. 2017 Apr 11;22(4):E617.[Abstract][Full Text]
50. Pouplard C, Amiral J, Borg JY, et al. Decision analysis for use of platelet aggregation test, carbon 14-serotonin release assay, and heparin-platelet factor 4 enzyme-linked immunosorbent assay for diagnosis of heparin-induced thrombocytopenia. Am J Clin Pathol. 1999 May;111(5):700-6.[Abstract]
51. Raschke RA, Gallo T, Curry SC, et al. Clinical effectiveness of a Bayesian algorithm for the diagnosis and management of heparin-induced thrombocytopenia. J Thromb Haemost. 2017 Aug;15(8):1640-5.[Abstract]
52. Linkins LA. Heparin induced thrombocytopenia. BMJ. 2015 Jan 8;350:g7566.[Abstract]
53. Greinacher A, Farner B, Kroll H, et al. Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis. A retrospective analysis of 408 patients. Thromb Haemost. 2005 Jul;94(1):132-5.[Abstract]
54. Vayne C, Guéry EA, Rollin J, et al. Pathophysiology and diagnosis of drug-induced immune thrombocytopenia. J Clin Med. 2020 Jul 13;9(7):2212.[Abstract][Full Text]
55. Warkentin TE. Heparin-induced thrombocytopenia. Curr Hematol Rep. 2002 Sep;1(1):63-72.[Abstract]
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58. Srinivasan AF, Rice L, Bartholomew JR, et al. Warfarin-induced skin necrosis and venous limb gangrene in the setting of heparin-induced thrombocytopenia. Arch Intern Med. 2004 Jan 12;164(1):66-70.[Abstract][Full Text]
59. Warkentin TE, Pai M, Linkins LA. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review. Blood. 2017 Aug 31;130(9):1104-13.[Abstract][Full Text]
60. Morgan RL, Ashoorion V, Cuker A, et al. Management of heparin-induced thrombocytopenia: systematic reviews and meta-analyses. Blood Adv. 2020 Oct 27;4(20):5184-93.[Abstract][Full Text]
61. Linkins LA, Warkentin TE, Pai M, et al. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study. J Thromb Haemost. 2016 Jun;14(6):1206-10.[Abstract]
62. Casan JM, Grigoriadis G, Chan N, et al. Rivaroxaban in treatment refractory heparin-induced thrombocytopenia. BMJ Case Rep. 2016 Aug 12;2016.[Abstract]
63. Kanamoto R, Hiromatsu S, Anegawa T, et al. Use of edoxaban for the treatment of heparin-induced thrombocytopenia. Case Rep Vasc Med. 2020 Sep 7;2020:2367095.[Abstract][Full Text]
64. Chaudhary RK, Nepal C, Khanal N, et al. Management and outcome of heparin-induced thrombocytopenia in pregnancy: a systematic review. Cardiovasc Hematol Agents Med Chem. 2015;13(2):92-7.[Abstract]
65. Koster A, Selleng S. Management of intraoperative anticoagulation in patients with heparin-induced thrombocytopenia undergoing surgery. In: Warkentin TE, Greinacher A, eds. Heparin-induced thrombocytopenia. 5th ed. Boca Raton, FL: Informa Healthcare; 2013:550-72.
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