Heparin induced thrombocytopenia and up to date options of treatment – review of literature

Czech version

Authors: Juraj Sokol ¹; František Nehaj ²; Juraj Chudej ¹; Michal Mokáň ²; Marianna Kubašková ³; Martin Jozef Péč ⁴; Jana Žolková ¹; Ubica Vadelová ¹; Peter Galajda ²; Ján Staško ¹
Authors‘ workplace: Klinika hematológie a transfuziológie, Národné centrum hemostázy a trombózy, JLF UK a UN Martin, Slovenská republika ¹; I. interná klinika JLF UK a UK Martin, Slovenská republika ²; Rádiologická klinika JLF UK a UN Martin, Slovenská republika ³; JLF UK Martin, Slovenská republika ⁴
Published in: Vnitř Lék 2020; 66(8): 39-46
Category:

Overview

Heparin-induced thrombocytopenia (HIT) is a profoundly dangerous, potentially lethal, immunologically mediated adverse drug reaction to unfractionated heparin or, less commonly, to low–molecular weight heparin. Some patients with HIT develop serious thrombotic complications like limb ischemia and gangrene, while others may not develop such complications. Current laboratory diagnostic tools incur significant time delays before confirming HIT, therefore upon clinical suspicion, treatment of HIT should start immediately. In this review, the authors highlight heparin-induced thrombocytopenia’s risk factors, clinical presentation, pathophysiology, diagnostic principles, and treatment.

Keywords:

Thrombocytopenia – autoimmunity – treatment – direct oral anticoagulants

Sources

1. Fathi M. Heparin‑induced thrombocytopenia (HIT): Identification and treatment pathways. Glob Cardiol Sci Pract 2018; 2: 1–13.

2. Arnold DM, Kelton JG. Heparin induced thrombocytopenia: an iceberg rising. Mayo Clin Proc 2005; 80: 988–990.

3. WarkentinTE, Sheppard J‑AI, Heels‑Ansdell D, et al. Heparin‑induced thrombocytopenia in medical surgical critical illness. Chest 2013; 144: 848–858.

4. Kanaan AO, Al‑Homsi AS. Heparin‑induced thrombocytopenia: Pathophysiology, diagnosis, and review of pharmacotherapy. J Pharm Pract 2009; 22: 149–157.

5. Greinacher A, Levy JH. HIT happens: diagnosing and evaluating the patient with heparin‑induced thrombocytopenia. Anesth Analg 2008; 107: 356–358.

6. Salter BS, Weiner MM, Trinh MA, et al. Heparin‑Induced Thrombocytopenia: A Comprehensive Clinical Review. J Am Coll Cardiol 2016; 67: 2519–2532.

7. Battistelli S, Genovese A, Gori T. Heparin‑induced thrombocytopenia in surgical patients. Am J Surg 2010; 199: 43–51.

8. Lovecchio F. Heparin‑induced thrombocytopenia. Clin Toxicol (Phila) 2014; 52: 579–583.

9. Sachais BS, Rux AH, Cines DB, et al. Rational design and characterization of platelet factor 4 antagonists for the study of heparin‑induced thrombocytopenia. Blood 2012; 119: 5955–5962.

10. Szokol JW. Heparin‑induced thrombocytopenia. Semin Cardiothorac Vasc Anesth 2010; 14: 73–74.

11. Walenga JM, Jeske WP, Messmore HL. Mechanisms of venous and arterial thrombosis in heparin‑induced thrombocytopenia. J Thromb Thrombolysis 2000; 10: (Suppl. 1):13–20.

12. Cuker A, Cines DB. How I treat heparin‑induced thrombocytopenia. Blood 2012; 119: 2209–2218.

13. Crespo EM, Oliveira GBF, Honeycutt EF, et al. for the CATCH Registry Investigators. Evaluation and management of thrombocytopenia and suspected heparin‑induced thrombocytopenia in hospitalized patients: the Complications After Thrombocytopenia Caused by Heparin (CATCH) registry. Am Heart J 2009; 157: 651–657.

14. Kato S, Takahashi K, Ayabe K, et al. Heparin‑induced thrombocytopenia: analysis of risk factors in medical inpatients. Br J Haematol 2011; 154: 373–377.

15. Martel N, Lee J, Wells PS. Risk for heparin‑induced thrombocytopenia with unfractionated and low‑molecular‑weight heparin thromboprophylaxis: a meta‑analysis. Blood 2005; 106: 2710–2715.

16. Arepally GM, Ortel TL. Heparin‑induced thrombocytopenia. Annu Rev Med 2010; 61: 77–90.

17. Visentin GP, Malik M, Cyganiak KA, et al. Patients treated with unfractionated heparin during open heart surgery are at high risk to form antibodies reactive with heparin: platelet factor 4 complexes. J Lab Clin Med 1996; 128: 376–383.

19. Prandoni P, Siragusa S, Girolami B, et al. for the BELZONI Investigators Group. The incidence of heparin‑induced thrombocytopenia in medical patients treated with low‑molecular‑weight heparin: a prospective cohort study. Blood 2005; 106: 3049–3054.

20. Warkentin TE. Fondaparinux: does it cause HIT? Can it treat HIT? Expert Rev Hematol 2010; 3: 567–581.

21. Francis JL, Palmer GJ III, Moroose R, et al. Comparison of bovine and porcine heparin in heparin antibody formation after cardiac surgery. Ann Thorac Surg 2003; 75: 17–22.

22. Selleng K, Warkentin TE, Greinacher A. Heparin‑induced thrombocytopenia in intensive care patients. Crit Care Med 2007; 35: 1165–1176.

23. Warkentin TE. Heparin‑induced thrombocytopenia in critically ill patients. Crit Care Clin 2011; 27: 805–823.

24. Warkentin TE, Sheppard JA, Horsewood P, et al. Impact of the patient population on the risk for heparin‑induced thrombocytopenia. Blood 2000; 96: 1703–1708.

25. Warkentin TE, Sheppard JAI, Sigouin CS, et al. Gender imbalance and risk factor interactions in heparin‑induced thrombocytopenia. Blood 2006; 108: 2937–2941.

26. Arepally GM. Heparin‑induced thrombocytopenia. Blood. 2017; 129: 2864–2872.

27. Amiral J, Peynaud‑Debayle E, Wolf M, et al. Generation of antibodies to heparin‑PF4 complexes without thrombocytopenia in patients treated with unfractionated or low‑molecular‑weight heparin. Am J Hematol 1996; 52: 90–95.

28. Warkentin TE, Sheppard JA, Horsewood P, et al. Impact of the patient population on the risk for heparin‑induced thrombocytopenia. Blood 2000; 96: 1703–1708.

29. Warkentin TE, Kelton JG. Temporal aspects of heparin‑induced thrombocytopenia. N Engl J Med 2001; 344: 1286–1292.

30. Warkentin TE, Greinacher A. Heparin‑induced thrombocytopenia and cardiac surgery. Ann Thorac Surg 2003; 76: 2121–2131.

31. Cuker A, Arepally G, Crowther MA, et al. The HIT Expert Probability (HEP) Score: a novel pre‑test probability model for heparin‑induced thrombocytopenia based on broad expert opinion. J Thromb Haemost 2010; 8: 2642–2650.

32. Pouplard C, May MA, Regina S, et al. Changes in platelet count after cardiac surgery can effectively predict the development of pathogenic heparin‑dependent antibodies. Br J Haematol 2005; 128: 837–841.

33. Nuttall GA, Oliver jr. WC, Santrach PJ, et al. Patients with a history of type II heparin‑induced thrombocytopenia with thrombosis requiring cardiac surgery with cardiopulmonary bypass: a prospective observational case series. Anesth Analg 2003; 96: 344–350.

34. Lillo‑Le Louët A, Boutouyrie P, Alhenc‑Gelas M, et al. Diagnostic score for heparininduced thrombocytopenia after cardiopulmonary bypass. J Thromb Haemost 2004; 2: 1882–1888.

35. Shantsila E, Lip GYH, Chong BH. Heparin‑induced thrombocytopenia. A contemporary clinical approach to diagnosis and management. Chest 2009; 135: 1651–1664.

36. Warkentin TE, Levine MN, Hirsh J, et al. Heparin‑induced thrombocytopenia in pa‑ tients treated with low‑molecular‑weight heparin or unfractionated heparin. N Engl J Med 1995; 332: 1330–1335.

37. Ahmed I, Majeed A, Powell R. Heparin‑induced thrombocytopenia: diagnosis and management update. Postgrad Med J 2007; 83: 575–582.

38. Arepally GM, Ortel TL. Clinical practice. Heparin‑induced thrombocytopenia. N Engl J Med 2006; 355: 809–817.

39. Lo GK, Juhl D, Warkentin TE, 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; 4: 759–765.

40. Warkentin TE, Roberts RS, Hirsh J, et al. An improved definition of immune heparin‑induced thrombocytopenia in postoperative orthopedic patients. Arch Intern Med 2003; 163: 2518–2524.

41. Lazúr J. Heprínom indukovaná trombocytopénia. Interná med 2019; 19: 51–54.

42. Kubisz P, Hollý P, Staško J. Heparínom indukovaná trombocytopénia. In: Štvrtinová V et al. Venózny tromboembolizmus. Bratislava: SAP, 2018, 388 s.

43. Brieger DB, Mak KH, Kottke‑Marchant K, et al. Heparin‑induced thrombocytopenia. J Am Coll Cardiol 1998; 31: 1449–1459.

44. 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; 2: 3360–3392.

45. He Y, He H, Liu D, et al. Fondaparinux in a critically ill patient with heparin‑induced thrombocytopenia. Medicine 2018; 97: 37.

46. Linkins LA, Hu G, Warkentin TE. Systematic review of fondaparinux for heparin‑induced thrombocytopenia: When there are no randomized controlled trials. Res Pract Thromb Haemost 2018; 2: 678–683.

47. Al‑Eidan FAS, Alrawkan S, Alshammary H, et al. Comparison of argatroban and fondaparinux for the management of patients with isolated heparin‑induced thrombocytopenia. Ann Hematol 2018; 47: 12.

48. Skelley JW, Kyle JA, Roberts RA. Novel oral anticoagulants for heparin‑induced thrombocytopenia. J Thromb Thrombolysis 2016; 42: 172–178.

49. Sokol J, Nehaj F, Mokán M, et al. Nové perorálne antikoagulanciá. Martin: Osveta. 2018. s. 266.

50. Walenga JM, Prechel M, Jeske WP, et al. Rivaroxaban - an oral, direct Factor Xa inhibi‑ tor - has potential for the management of patients with heparin‑induced thrombocytopenia. Br J Haematol 2008; 143: 92–99.

51. Walenga JM, Prechel M, Hoppensteadt D, et al. Apixaban as an alternate oral anticoagulant for the management of patients with heparin‑induced thrombocytopenia. Clin Appl Thromb Hemost 2013; 19: 482–487.

52. Linkins LA, Warkentin TE, Pai M, et al. Design of the rivaroxaban for heparin‑induced thrombocytopenia study. J Thromb Thrombolysis 2014; 38: 485–492.

53. Aljabri A, Huckleberry Y, Karnes JH, et al. Cost‑effectiveness of anticoagulants for suspected heparin‑induced thrombocytopenia in the United States. Blood 2016; 128: 3043–3051.

54. Linkins LA, Warkentin TE, Pai M, et al. Abstract number 3468 Rivaroxaban for Treatment of Suspected or Confirmed Heparin‑Induced Thrombocytopenia Study. American Socie‑ ty of Hematology 57th annual meeting Orlando FL, 2016.

55. Warkentin TE, Pai M, Linkins LA. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review. Blood 2017; 130: 1104–1113.

56. Shatzel JJ, Crapster‑Pregont M, Deloughery TG. Non‑vitamin K antagonist oral anticoagulants for heparin‑induced thrombocytopenia. A systematic review of 54 reported cases. Thromb Haemost 2016; 116: 397–400.

57. Kunk P, Macik BG, Brown J. Abstract number 3547 Non‑Warfarin Oral Anticoagulants in Heparin‑Induced Thrombocytopenia. American Society of Hematology 57th annual meeting Orlando FL, 2015.

58. Ng HJ, Than H, Teo EC First experiences with the use of rivaroxaban in the treatment of heparin‑induced thrombocytopenia. Thromb Res 2015; 135: 205–207.

59. Mirdamadi A Dabigatran, a direct thrombin inhibitor, can be a life‑saving treatment in heparin‑induced thrombocytopenia. ARYA Atheroscler 2013; 9: 112–114.

60. Hantson P, Lambert C, Hermans C. Rivaroxaban for arterial thrombosis related to heparin‑induced thrombocytopenia. Blood Coagul Fibrinolysis 2015; 26: 205–206.

61. Sartori M, Favaretto E, Cini M, et al. Rivaroxaban in the Treatment of Heparin‑Induced Thrombocytopenia. J Thromb Thrombolysis 2015; 40: 392–394.

62. Larsen PB, Jørgensen M, Friis‑Hansen L, et al. Apixaban used for the management of heparin‑induced thrombocytopenia in a 72-year‑old woman with lung cancer. Clin Case Rep 2015; 3: 987–989.

63. Sharifi M, Bay C, Vajo Z, et al. New oral anticoagulants in the treatment of heparin‑induced thrombocytopenia. Thromb Res 2015; 135: 607–609.

64. Abouchakra L, Khabbaz Z, Abouassi S, et al. Rivaroxaban for treatment of heparin‑induced throm- bocytopenia after cardiac surgery: A case report. J Thorac Cardiovasc Surg 2015; 150: e19–e20.

65. Kopolovic I, Warkentin TE. Progressive thrombocytopenia after cardiac surgery in a 67-year‑old man. CMAJ 2014; 186: 929–933.

66. Sninská Z, Chudej J, Guman T, et al. Primárna imúnna trombocytopénia: princípy klasifikácie, diagnostiky a liečby. Bratislava: GlaxoSmithKline Slovensko, 2014, 57 s.

67. Majdák P, Kubík jr. J, Harmátová L. Prípad vlajúceho infikovaného trombu v. jugularis interna, septických pneumónií a heparínom indukovanej trombocytopénie. Vnitř Lék 2011; 57: 117–121.

68. Sárník S, Hofírek I. Opakovaná lokální trombolýza u poranení a trombózy axilární a pod‑ klíckové zíly. Vnitř Lék 2009; 55: 1102–1104.

69. Dulíček P, Chrobák L. Trombocytopenie indukovaná heparinem.