, Volume 25, Issue 11, pp 949–961 | Cite as

Strategies for the Management of Suspected Heparin-Induced Thrombocytopenia

A Cost-Effectiveness Analysis
  • Amanda R. Patrick
  • Wolfgang C. Winkelmayer
  • Jerry Avorn
  • Michael A. Fischer
Original Research Article


Background: Heparin-induced thrombocytopenia (HIT) is a rare but serious complication of heparin therapy. The diagnosis of HIT is difficult because its signs are non-specific and the heparin-platelet factor 4 (PF4) antibody test used to confirm the diagnosis is imprecise. Drugs used to treat HIT are costly and may carry an increased risk of bleeding.

Objective: To evaluate the cost effectiveness, from a societal perspective, of four treatment approaches for patients with suspected HIT within a US critical care setting.

Methods: A decision-tree was constructed for the management of a hypothetical cohort of critical care patients with possible evidence of HIT.

The management strategies were: (i) no antibody testing, continue heparin (No Test and Wait); (ii) antibody testing, continue heparin while test results pending (Test and Wait); (iii) antibody testing and switch to a direct thrombin inhibitor (DTI) while test results pending (Test and Switch); and (iv) no antibody testing but switch to a DTI (No Test and Switch). We used argatroban as the DTI in our analysis.

The outcomes were direct medical costs ($US; 2004 values), QALYs and incremental cost-effectiveness ratios (ICERs).

Results: Assuming an HIT prevalence of 3%, relative to less costly strategies, ordering an antibody test and switching patients to argatroban if the result was positive (Test and Wait) had an ICER of $US163 396/QALY. Pre-emptive switching to argatroban without antibody testing (No Test and Switch) was the most effective strategy but had an ICER of >$US1 million/QALY relative to the Test and Switch option. These results were highly sensitive to HIT prevalence among patients presenting with thrombocytopenia.

Assuming a willingness to pay of $US50 000 per QALY, the Test and Wait strategy became cost effective when the prior probability of HIT was 8%. At a prior probability of 12%, Test and Switch was cost effective, and at probabilities of HIT in the 60–75% range, No Test and Switch was cost effective. In two-way analysis, the probability of developing a thrombotic event was a key driver of treatment choice at specific HIT probabilities.

Conclusions: Testing for HIT in all typical critical care patients with thrombocytopenia is unlikely to represent a cost-effective management strategy. With increasing probability of HIT, strategies that include testing and a more rapid switch to a DTI appear more desirable. Accurate clinical judgment of the prior probability of HIT has a critical influence on the cost-effective management of HIT.


  1. 1.
    Warkentin TE. Heparin-induced thrombocytopenia: pathogenesis and management. Br J Haematol 2003; 121 (4): 535–555PubMedCrossRefGoogle Scholar
  2. 2.
    Warkentin TE. New approaches to the diagnosis of heparin-induced thrombocytopenia. Chest 2005; 127 (2): 35S–45SPubMedCrossRefGoogle Scholar
  3. 3.
    Verma AK, Levine M, Shalansky S J, et al. Frequency of heparin-induced thrombocytopenia in critical care patients. Pharmacotherapy 2003; 23 (6): 745–753PubMedCrossRefGoogle Scholar
  4. 4.
    Crowther MA, Cook DJ, Meade MO, et al. Thrombocytopenia in medical-surgical critically ill patients: prevalence, incidence, and risk factors. J Crit Care 2005; 20 (4): 348–353PubMedCrossRefGoogle Scholar
  5. 5.
    Warkentin TE, Greinacher A. Heparin-induced thrombo-cytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (3 Suppl.): 311S–371SPubMedCrossRefGoogle Scholar
  6. 6.
    Call JT, Deliargyris EN, Sane DC. Direct thrombin inhibitors in the treatment of immune-mediated heparin-induced thrombocytopenia. Semin Thromb Hemost 2004; 30 (3): 297–314PubMedCrossRefGoogle Scholar
  7. 7.
    Thomson Corporation. Drug Topics Red book. Montvale (NJ): Thomson PDR, 2004: vGoogle Scholar
  8. 8.
    Gold MR, Siegel JE Russell LB, Weinstein MC. Cost-effectiveness in health and medicine. New York: Oxford University Press, 1996Google Scholar
  9. 9.
    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 1995; 332 (20): 1330–1335PubMedCrossRefGoogle Scholar
  10. 10.
    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 (20): 2518–2524PubMedCrossRefGoogle Scholar
  11. 11.
    Greinacher A, Eichler P, Lubenow N, et al. 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 (3): 846–851PubMedGoogle Scholar
  12. 12.
    Lewis BE, Wallis DE, Berkowitz SD, et al. Argatroban antico-agulant therapy in patients with heparin-induced thrombocytopenia. Circulation 2001; 103 (14): 1838–1843PubMedCrossRefGoogle Scholar
  13. 13.
    Lewis BE, Wallis DE, Leya F, et al. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med 2003; 163 (15): 1849–1856PubMedCrossRefGoogle Scholar
  14. 14.
    Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med 1996; 101 (5): 502–507PubMedCrossRefGoogle Scholar
  15. 15.
    Wallis DE, Workman DL, Lewis BE, et al. Failure of early heparin cessation as treatment for heparin-induced thrombocytopenia. Am J Med 1999; 106 (6): 629–635PubMedCrossRefGoogle Scholar
  16. 16.
    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; 94 (1): 132–135PubMedGoogle Scholar
  17. 17.
    Petersen JL, Mahaffey KW, Hasselblad V, et al. Efficacy and bleeding complications among patients randomized to enox-aparin or unfractionated heparin for antithrombin therapy in non-ST-Segment elevation acute coronary syndromes: a systematic overview. JAMA 2004; 292 (1): 89–96PubMedCrossRefGoogle Scholar
  18. 18.
    Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. Am J Med 1993; 95 (3): 315–328PubMedCrossRefGoogle Scholar
  19. 19.
    Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial. Circulation 1999; 100 (15): 1593–1601PubMedCrossRefGoogle Scholar
  20. 20.
    Levine MN, Raskob G, Landefeld S, et al. Hemorrhagic complications of anticoagulant treatment. Chest 1995; 108 (4 Suppl.): 276S–290SPubMedCrossRefGoogle Scholar
  21. 21.
    Juergens CP, Semsarian C, Keech AC, et al. Hemorrhagic complications of intravenous heparin use. Am J Cardiol 1997; 80 (2): 150–154PubMedCrossRefGoogle Scholar
  22. 22.
    Raschke RA, Reilly BM, Guidry JR, et al. The weight-based heparin dosing nomogram compared with a “standard care” nomogram: a randomized controlled trial. Ann Intern Med 1993; 11 (9): 874–881Google Scholar
  23. 23.
    Mismetti P, Laporte-Simitsidis S, Tardy B, et al. Prevention of venous mromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 2000; 83 (1): 14–19PubMedGoogle Scholar
  24. 24.
    Levine MN, Raskob G, Beyth RJ, et al. Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (3 Suppl.): 287S–310SPubMedCrossRefGoogle Scholar
  25. 25.
    Moledina M, Chakir M, Gandhi PJ. A synopsis of the clinical uses of argatroban. J Thromb Haemost 2001; 12 (2): 141–149Google Scholar
  26. 26.
    Warkentin TE. Platelet count monitoring and laboratory testing for heparin-induced thrombocytopenia. Arch Pathol Lab Med 2002; 126 (11): 1415–1423PubMedGoogle Scholar
  27. 27.
    Menzin J, Colditz GA, Regan MM, et al. Cost-effectiveness of enoxaparin vs low-dose warfarin in the prevention of deep-vein thrombosis after total hip replacement surgery. Arch Intern Med 1995; 155 (7): 757–764PubMedCrossRefGoogle Scholar
  28. 28.
    Devlin JW, Petitta A, Shepard AD, et al. Cost-effectiveness of enoxaparin versus low-dose heparin for prophylaxis against venous thrombosis after major trauma. Pharmacotherapy 1998; 18 (6): 1335–1342PubMedGoogle Scholar
  29. 29.
    Gould MK, Dembitzer AD, Sanders GD, et al. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis: a cost-effectiveness analysis. Ann Intern Med 1999; 130 (10): 789–799PubMedGoogle Scholar
  30. 30.
    O’Brien JA, Patrick AR, Caro J. Estimates of direct medical costs for microvascular and macrovascular complications resulting from type 2 diabetes mellitus in the United States in 2000. Clin Ther 2003; 25 (3): 1017–1038PubMedCrossRefGoogle Scholar
  31. 31.
    O’Brien JA, Caro JJ. Direct medical cost of managing deep vein thrombosis according to the occurrence of complications. Pharmacoeconomics 2002; 20 (9): 603–615PubMedCrossRefGoogle Scholar
  32. 32.
    Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular-weight heparin vs warfarin for prophylaxis of deep vein thrombosis after hip or knee implantation. An economic perspective. Arch Intern Med 1997; 157 (3): 298–303PubMedCrossRefGoogle Scholar
  33. 33.
    Fryback DG, Dasbach EJ, Klein R, et al. The Beaver Dam Health Outcomes Study: initial catalog of health-state quality factors. Med Decis Making 1993; 13 (2): 89–102PubMedCrossRefGoogle Scholar
  34. 34.
    Hunink MG, Wong JB, Donaldson MC, et al. Revascularization for femoropopliteal disease. A decision and cost-effectiveness analysis. JAMA 1995; 274 (2): 165–171PubMedCrossRefGoogle Scholar
  35. 35.
    Clarke P, Gray A, Holman R. Estimating utility values for health states of type 2 diabetic patients using the EQ-5D (UKPDS 62). Med Decis Making 2002; 22 (4): 340–349PubMedGoogle Scholar
  36. 36.
    Sculpher M, Michaels J, McKenna M, et al. A cost-utility analysis of laser-assisted angioplasty for peripheral arterial occlusions. Int J Technol Assess Health Care 1996; 12 (1): 104–125PubMedCrossRefGoogle Scholar
  37. 37.
    Eckman MH, Greenfield S, Mac key WC, et al. Foot infections in diabetic patients: decision and cost-effectiveness analyses. JAMA 1995; 273 (9): 712–720PubMedCrossRefGoogle Scholar
  38. 38.
    Brothers TE, Cox MH, Robison JG, et al. Prospective decision analysis modeling indicates that clinical decisions in vascular surgery often fail to maximize patient expected utility. J Surg Res 2004; 120 (2): 278–287PubMedCrossRefGoogle Scholar
  39. 39.
    CEA Registry. Catalog of Preference Scores. Vol 2004 [online]. Available from URL: [Accessed 2007 Sep 24]Google Scholar
  40. 40.
    Tengs TO, Yu M, Luistro E. Health-related quality of life after stroke a comprehensive review. Stroke 2001; 32 (4): 964–972PubMedCrossRefGoogle Scholar
  41. 41.
    Arias E. United States life tables, 2002. National Vital Statistics Reports; vol 53 no 6. Hyattsville (MD): National Center for Health Statistics, 2004Google Scholar
  42. 42.
    Center on the Evaluation of Value and Risk in Health. The cost-effectiveness analysis registry. Boston: Tufts-New England Medical Center, ICRHPS [online]. Available from URL: [Accessed 2007 Oct 25]Google Scholar
  43. 43.
    Laupacis A, Feeny D, Detsky AS, et al. How attractive does a new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. CMAJ 1992; 146 (4): 473–481PubMedGoogle Scholar
  44. 44.
    Winkelmayer WC, Weinstein MC, Mittleman MA, et al. Health economic evaluations: the special case of end-stage renal disease treatment. Med Decis Making 2002; 22 (5): 417–430PubMedGoogle Scholar
  45. 45.
    Warkentin TE, Aird WC, Rand JH. Platelet-endothelial interactions: sepsis, HIT, and antiphospholipid syndrome. Hematology (Am See Hematol Educ Program) 2003: 497–519Google Scholar
  46. 46.
    Jang IK, Brown DF, Giugliano RP, et al. A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with novastan and TPA (MINT) study. J Am Coll Cardiol 1999; 33 (7): 1879–1885PubMedCrossRefGoogle Scholar
  47. 47.
    Hirahara T, Kubo N, Ohmura N, et al. Prospective randomized study of argatroban versus heparin anticoagulation therapy after percutaneous coronary intervention for acute myocardial infarction [in Japanese]. J Cardiol 2004; 44 (2): 47–52PubMedGoogle Scholar
  48. 48.
    Fanikos J, Stapinski C, Koo S, et al. Medication errors associated with anticoagulant therapy in the hospital. Am J Cardiol 2004; 94 (4): 532–535PubMedCrossRefGoogle Scholar
  49. 49.
    Lube now 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 (HIT) [abstract]. Blood 2002; 100: 502aGoogle Scholar
  50. 50.
    Lube now N, Eichler P, Lietz T, et al. Lepirudin in patients with heparin-induced thrombocytopenia: results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3. J Thromb Haemost 2005; 3 (11): 2428–2436CrossRefGoogle Scholar
  51. 51.
    Warkentin TW. Thrombotic end point for assessing argatroban therapy for heparin-induced thrombocytopenia: learning from secondary analyses of prospective studies. Chest 2006; 129 (6): 1396–1398PubMedCrossRefGoogle Scholar
  52. 52.
    Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006; 354 (4): 353–365PubMedCrossRefGoogle Scholar
  53. 53.
    Parody R, Oliver A, Souto JC, et al. Fondaparinux (ARIXTRA) as an alternative anti-thrombotic prophylaxis when there is hypersensitivity to low molecular weight and unfractionated heparins. Haematologica 2003; 88 (11): ECR32PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Amanda R. Patrick
    • 1
  • Wolfgang C. Winkelmayer
    • 1
  • Jerry Avorn
    • 1
  • Michael A. Fischer
    • 1
  1. 1.Division of Pharmacoepidemiology and PharmacoeconomicsBrigham and Women’s HospitalBostonUSA

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