Journal of Thrombosis and Thrombolysis

, Volume 26, Issue 2, pp 125–131 | Cite as

Cost and occurrence of thrombocytopenia in patients receiving venous thromboembolism prophylaxis following major orthopaedic surgeries

  • Laura Elizabeth Happe
  • Eileen Marie Farrelly
  • Richard H. Stanford
  • Matt William Sarnes


Background Many factors impact the choice of anticoagulant used for venous thromboembolism prophylaxis following orthopaedic surgery. Thrombocytopenia (TCP) is an important factor from both clinical and economic perspectives, warranting assessment between the available agents. Thus, a retrospective cohort analysis was conducted to: (1) report the occurrence of TCP in a treatment and no treatment group, (2) evaluate the impact of anticoagulant choice on TCP within the treatment group, and (3) assess the clinical and economic implications of TCP in the treatment group. Methods Administrative claims from a hospital database were used to identify patients with hip replacement, knee replacement, or hip fracture surgery. The treatment group (n = 144,806) included patients receiving one of the following injectable anticoagulants post-operatively: dalteparin (n = 16,109); enoxaparin (n = 97,827); fondaparinux (n = 12,532); or unfractionated heparin (UFH) (n = 18,338). The no treatment group consisted of patients who did not receive one of the four injectable anticoagulants (n = 112,574) post-operatively. Outcomes were assessed for the hospitalization period plus 2 months post-discharge while controlling for relevant demographic and clinical characteristics. Results The occurrence of TCP was 1.0% in the no treatment group and 1.7% in the treatment group. Within the treatment group, patients who received dalteparin, enoxaparin, and UFH were significantly more likely to experience coded thrombocytopenia than those in the no treatment group. The risk of TCP among patients who received fondaparinux was not significantly different from the no treatment cohort (odds ratio [OR] = 1.15, 95% CI: 0.96–1.37, P = 0.13). Patients in the treatment group with coded TCP had 22% higher adjusted mean total healthcare costs (relative cost difference) compared to those without ($19,134 vs. $15,400, respectively, P < 0.0001), greater mean length of stay (LOS) (8.4 vs. 5.7, respectively), and a greater likelihood of experiencing a venous thromboembolic (VTE) event (6.1% vs. 2.4%, respectively). Conclusion Patients treated with fondaparinux did not have a significant increase in the risk of TCP compared to patients not on prophylaxis. In contrast, the risk was increased in those treated with enoxaparin, dalteparin, and UFH compared to the patients not on prophylaxis. Patients in the treatment group with coded TCP experienced more thrombotic events, incurred greater per patient healthcare costs, and experienced longer LOS than patients without coded TCP. Therefore, the risk of TCP should be considered when evaluating the profile of injectable anticoagulants since TCP may have important clinical and economic implications.


Thrombocytopenia Heparin Orthopaedic surgery Healthcare cost Venous thromboembolism Outcomes Incidence Anticoagulant Fondaparinux 



Funding for the study and the manuscript was provided by GlaxoSmithKline. The manuscript was reviewed by Sarah A. Spinler, PharmD, FCCP, BCPS, Philadelphia College of Pharmacy.


  1. 1.
    Warkentin TE, Roberts RS, Hirsh J, Kelton JG (2003). An improved definition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients. Arch Intern Med 163:2518–2524PubMedCrossRefGoogle Scholar
  2. 2.
    Merck Manual Online Medical Library (2006) Thrombocytopenia. Available from Accessed August 21, 2006
  3. 3.
    Eichler P, Raschke R, Lubenow N, Meyer O, Schwind P, Greinacher A (2002) The new ID-heparin/PF4 antibody test for rapid detection of heparin-induced antibodies in comparison with functional and antigenic assays. Br J Haematol 116:887–891PubMedCrossRefGoogle Scholar
  4. 4.
    Kelton JG (1999) The clinical management of heparin-induced thrombocytopenia. Semin Hematol 36(suppl 1):17–21PubMedGoogle Scholar
  5. 5.
    King DJ, Kelton JG (1984) Heparin-associated thrombocytopenia. Ann Intern Med 100:535–540PubMedGoogle Scholar
  6. 6.
    Spinler SA, Dager W (2003) Overview of heparin-induced thrombocytopenia. Am J Health Syst Pharm 60(Suppl 5):S5–11PubMedGoogle Scholar
  7. 7.
    Visentin GP (1999) Heparin-induced thrombocytopenia: molecular pathogenesis. Semin Thrombos Haemostas 82:448–456Google Scholar
  8. 8.
    Warkentin TE, Greinacher A (2004) Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 126(Suppl 3):311–337CrossRefGoogle Scholar
  9. 9.
    Martel N, Lee J, Wells PS (2005) Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood 106:2710–2715PubMedCrossRefGoogle Scholar
  10. 10.
    Geerts WH, Pineo GF, Heit JA et al (2004) Prevention of venous thromboembolism: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 126(3 Suppl):S338–400CrossRefGoogle Scholar
  11. 11.
    Efird LE, Kockler DR (2006) Fondaparinux for thromboembolic treatment and prophylaxis of heparin-induced thrombocytopenia. Ann Pharmacother 40:1383–1387PubMedCrossRefGoogle Scholar
  12. 12.
    Boon DM, Michels JJ, Stibbe J, van Vliet HH, Kappers-Klune MC (1994) Heparin-induced thrombocytopenia and antithrombotic therapy (letter). Lancet 344:1296PubMedCrossRefGoogle Scholar
  13. 13.
    Greinacher A, Eichler P, Lubenow N, Kwasng H, Luz M (2000) 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 96:846–851PubMedGoogle Scholar
  14. 14.
    Warkentin TE (2005) New approaches to the diagnosis of heparin-induced thrombocytopenia. Chest 127(2 suppl):35S–45SPubMedCrossRefGoogle Scholar
  15. 15.
    Girolami B, Prandoni P, Stefani PM et al (2003) The incidence of heparin-induced thrombocytopenia in hospitalized medical patients treated with subcutaneous unfractionated heparin: a prospective cohort study. Blood 101:2955–2959PubMedCrossRefGoogle Scholar
  16. 16.
    Warkentin TE, Greinacher A (2001) Clinical picture of heparin-induced thrombocytopenia. In: Heparin-induced thrombocytopenia, 2nd edn. Marcel Dekker Inc., New York, pp 43–86Google Scholar
  17. 17.
    Hirsh J, Heddle N, Kelton JG (2004) Treatment of heparin-induced thrombocytopenia. Arch Intern Med 164:361–369PubMedCrossRefGoogle Scholar
  18. 18.
    O’Brien JA, Caro JJ (2002) Direct medical cost of managing deep vein thrombosis according to the occurrence of complications. Pharmacoeconomics 20:603–615PubMedCrossRefGoogle Scholar
  19. 19.
    Creekmore FM, Oderda GM, Pendleton RC, Brixner DI (2006) Incidence and economic implications of heparin-induced thrombocytopenia in medical patients receiving prophylaxis for venous thromboembolism. Pharmacotherapy 26(10):1438–1445PubMedCrossRefGoogle Scholar
  20. 20.
    Bussey H, Francis JL, the Heparin Consensus Group (2004) Heparin overview and issues. Pharmacotherapy 24(8 pt 2):S103–107CrossRefGoogle Scholar
  21. 21.
    Savi P, Chong BH, Greinacher A et al (2005) Effect of fondaparinux on platelet activation in the presence of heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin. Blood 105:139–144PubMedCrossRefGoogle Scholar
  22. 22.
    Lindenauer PK, Pekow P, Wang K, Mamidi DK, Gutierrez B, Benjamin EM (2005) Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N Engl J Med 353:349–361PubMedCrossRefGoogle Scholar
  23. 23.
    Ouriel K, Kaul AF, Leonard MC (2004) Clinical and economic outcomes in thrombolytic treatment of peripheral arterial occlusive disease and deep venous thrombosis. J Vasc Surg 40:971–977PubMedCrossRefGoogle Scholar
  24. 24.
    Orrick JJ, Segal R, Johns TE, Russell W, Wang F, Yin DD (2004) Resource use and cost of care for patients hospitalized with community acquired pneumonia: impact of adherence to Infectious Diseases Society of America guidelines. Pharmacoeconomics 22:751–757PubMedCrossRefGoogle Scholar
  25. 25.
    Deyo RA, Cherkin DC, Ciol MA (1992) Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 45:613–619PubMedCrossRefGoogle Scholar
  26. 26.
    Bernardini J, Callen S, Fried L, Piraino B (2004) Inter-rater reliability and annual rescoring of the Charlson comorbidity index. Adv Perit Dial 20:125–127PubMedGoogle Scholar
  27. 27.
    Roos LL, Sharp SM, Cohen MM (1991) Comparing clinical information with claims data: some similarities and differences. J Clin Epidemiol 44(9):881–888PubMedCrossRefGoogle Scholar
  28. 28.
    Roos LL, Sharp SM, Cohen MM, Wajda A (1989) Risk adjustment in claims-based research: the search for efficient approaches. J Clin Epidemiol 42:1193–1206PubMedCrossRefGoogle Scholar
  29. 29.
    O’Connor GT, Plume SK, Olmstead EM et al (1991) A regional prospective study of in-hospital mortality associated with coronary artery bypass grafting. The Northern New England Cardiovascular Disease Study Group. JAMA 266:803–809PubMedCrossRefGoogle Scholar
  30. 30.
    Warkentin TE, Levine MN, Hirsch J et al (1995) Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 332:1330–1335PubMedCrossRefGoogle Scholar
  31. 31.
    Warkentin TE, Kelton JG (1996) A 14-year study of heparin-induced thrombocytopenia. Am J Med 101:502–507PubMedCrossRefGoogle Scholar
  32. 32.
    Frame JN (2005) The heparin-induced thrombocytopenia task force model: implementing quality improvement and economic outcome initiatives. Semin Hematol 42(Suppl 3):S28–35PubMedCrossRefGoogle Scholar
  33. 33.
    Kang SK, Wordell CJ, Senholzi C, Chambers L (2004) Cost of enoxaparin for prevention and/or treatment of thromboembolic events vs. the cost of treating heparin-induced thrombocytopenia (HIT): a cost-benefit analysis [Abstract]. Presented at ASHP 39th midyear clinical meeting and exhibits, December 5–9, 2004, Orlando, FL. Available from hppt:// Abstract MCS-18. Accessed January 19, 2007Google Scholar
  34. 34.
    Elting LS, Cantor SB, Martin CG et al (2003) Cost of chemotherapy-induced thrombocytopenia among patients with lymphoma or solid tumors. Cancer 97:1541–1550PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Laura Elizabeth Happe
    • 1
  • Eileen Marie Farrelly
    • 1
  • Richard H. Stanford
    • 2
  • Matt William Sarnes
    • 1
  1. 1.XcendaPalm HarborUSA
  2. 2.North American DivisionGlaxoSmithKline: Global Health OutcomesResearch Triangle ParkUSA

Personalised recommendations