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New Concepts in Heparin-Induced Thrombocytopenia: Diagnosis and Management

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Abstract

Heparin-induced thrombocytopenia (HIT) is a clinicopathologic condition and adverse drug reaction caused by immunoglobulin G (IgG) antibodies directed against the heparin-platelet factor 4 complex. In most patients, the onset of thrombocytopenia begins while the patient is receiving heparin. In less than 5% of patients, the onset of thrombocytopenia begins several days following heparin discontinuation and has been termed “delayed-onset” HIT. This review summarizes the presentation and clinical course of published reports of delayed-onset HIT occurring in 30 patients. The diagnosis of delayed-onset HIT should be considered in all patients presenting with venous thromboembolism (VTE) and all patients with recent heparin exposure (within the past 14 days) who present with a low platelet count.

Most patients with HIT are treated with direct thrombin inhibitors and transitioned to warfarin oral anticoagulation. Administration of direct thrombin inhibitors requires close monitoring for bleeding, dose adjustments based upon coagulation monitoring and is costly. Fondaparinux, a synthetic pentasaccharide and indirect-acting factor-Xa inhibitor, has little to no cross-reactivity with the heparin-platelet factor 4 antibody in in vitro testing. This review summarizes dosing, monitoring and outcomes of preliminary reports of fondaparinux successfully administered to 13 patients with subacute HIT and 22 patients with acute HIT. While several reports have described the treatment and prophylaxis of thrombosis in patients with HIT using fondaparinux, clinical trials should be conducted and reported before fondaparinux becomes a therapy of choice for HIT.

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References

  1. Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 Suppl):311S–337S.

    CAS  PubMed  Google Scholar 

  2. Refaai MA, Van Cott EM, Laposata M. The timing of a positive test result for heparin-induced thrombocytopenia relative to the platelet count and anticoagulant therapy in 43 consecutive cases. Am J Clin Pathol 2003;119:497–504.

    PubMed  Google Scholar 

  3. Warkentin TE. New approaches to the diagnosis of heparin-induced thrombocytopenia. Chest 2005;127(2 Suppl):35S–45S.

    CAS  PubMed  Google Scholar 

  4. Kelton JG. The pathophysiology of heparin-induced thrombocytopenia: biological basis for treatment. Chest 2005:127(2 Suppl):9S–20S.

    PubMed  Google Scholar 

  5. Rice L. Heparin-induced thrombocytopenia: myths and misconceptions (that will cause trouble for you and your patient). Arch Intern Med 2004;164:1961–1964.

    Article  PubMed  Google Scholar 

  6. Warkentin TE, Kelton JG. Delayed-onset heparin-induced thrombocytopenia and thrombosis. Ann Intern Med 2001;135:502–506.

    CAS  PubMed  Google Scholar 

  7. Rice L, Attisha WK, Drexler A, Francis JL. Delayed-onset heparin-induced thrombocytopenia. Ann Intern Med 2002;136:210–215.

    PubMed  Google Scholar 

  8. Shah MR, Spencer JP. Heparin-induced thrombocytopenia occurring after discontinuation of heparin. J Am Board Fam Pract 2003;16:148–150.

    PubMed  Google Scholar 

  9. Warkentin TE, Bernstein RA. Delayed-onset heparin-induced thrombocytopenia and cerebral thrombosis after a single administration of unfractionated heparin (Letter). N Engl J Med 2003;348:1067–1069.

    Article  PubMed  Google Scholar 

  10. Smythe MA, Stephens JL, Mattson JC. Delayed-onset heparin-induced thrombocytopenia. Ann Emerg Med 2005;45:417-19.

    Article  PubMed  Google Scholar 

  11. Hassell K. The management of patients with heparin-induced thrombocytopenia who require anticoagulant therapy. Chest 2005;127(2 Suppl):1S–8S.

    CAS  PubMed  Google Scholar 

  12. Spinler SA, Dagar W. Overview of heparin-induced thrombocytopenia. Am J Health Syst Pharm 2003;60 (Suppl 5):S5–11.

    CAS  PubMed  Google Scholar 

  13. ARIXTRA (fondaparinux sodium) Inection Prescribing Information. GlaxoSmithKline, Research Triangle Park, MC; May 2005.

    Google Scholar 

  14. 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 2005;105:139–144.

    Article  CAS  PubMed  Google Scholar 

  15. Greinacher A, Alban S, Dummel V, Franz G, Mueller-Eckhardt C. 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;74(3):886–892.

    CAS  PubMed  Google Scholar 

  16. Elalamy I, Lecrubier C, Potevin F, et al. Absence of in vitro cross-reaction of pentasaccharide with the plasma heparin-dependent factor of twenty-five patients with heparin-associated thrombocytopenia. Thromb Haemost 1995;74(5):1384–1385.

    CAS  PubMed  Google Scholar 

  17. 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 1997;8(2):114–117.

    CAS  PubMed  Google Scholar 

  18. Ahmad S, Jeske WP, Walenga JM, et al. Synthetic pentasaccharides do not cause platelet activation by antiheparin-platelet factor 4 antibodies. Clin Appl Thromb Hemost 1999;5(4):259–266.

    CAS  PubMed  Google Scholar 

  19. Harenberg J, Jorg I, Fenyvesi T, Hagedorn A, Giese C, Trager I. Prophylaxsi of recurrent thromboembolism in a patient with a history of heparin-induced thrombocytopenia with thrombosis, anti-lepirudin antibodies after Bjork-Shiley aortic valve implantation using fondaparinux. J Thrombos Haemost 2003(Suppl 1): Abstract P2040.

  20. D'Amico EA, Villaca PR, Gualandro FM, Bassitt RP, Chamone DAF. Successful use of Arixtra in a patients with paroxysmal nocturnal hemoglobinuria, Budd-Chiari syndrome and heparin-induced thrombocytopenia. J Thrombos Haemost 2003;1:2452–2453.

    Google Scholar 

  21. Lian EC, Chua L, Oberstein E. Long-term use of fondaparinux in a patients with antiphospholipid antibody sudrome, heparin-induced thrombocytopenia and regractoriness to coumarin (abstract). Blood 2003;102:4206.

    Google Scholar 

  22. Bradner J, Hallisey RK, Kuter DJ. Fondaparinux in the treatment of heparin-induced thrombocytopenia (abstract). Blood 2004;104(11):Abstract 4072.

    Google Scholar 

  23. Kuo KHM, Kovacs MJ. Successful treatment of heparin induced thrombocytopenia (HIT) with fondaparinux (abstract). Blood 2003;102:1147.

    Google Scholar 

  24. Rubin N, Rubin J. Treatment of heparin-induced thrombocytopenia with thrombosis (HITT) in pregnancy with fondaparinux (abstract). Blood 2003;102:4190.

    Google Scholar 

  25. Parody R, Oliver A, Souto JC, Fontcuberta J. Fondaparinux (ARIXTRA) as an alternative anti-thrombotic prophylaxis when there is hypersensitivity to low molecular weight and unfractionated heparins. Hematologica 2003;88(110):ECR32.

    Google Scholar 

  26. Haase M, Ellomo R, Rocktaeschel J, et al. Use of fondaparinux (ARIXTRA) in a dialysis patient with symptomatic heparin-induced thrombocytopenia type II. Nephrol Dial Transplant 2005;20:444–446.

    PubMed  Google Scholar 

  27. Kovacs MJ. Successful treatment of heparin-induced thrombocytopenia (HIT) with fondaparinux. Thromb Haemost 2005;93:999–1000.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, 600 S. 43rd St., Philadelphia, PA, 19104

    Sarah A. Spinler PharmD (Professor of Clinical Pharmacy, Adjunct Professor of Pharmacy in Medicine)

  2. Department of Pharmacy Practice and Pharmacy Administration, Department of Medicine, Cardiovascular Division, University of Pennsylvania, Pennsylvania

    Sarah A. Spinler PharmD (Professor of Clinical Pharmacy, Adjunct Professor of Pharmacy in Medicine)

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  1. Sarah A. Spinler PharmD
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Correspondence to Sarah A. Spinler PharmD.

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Spinler, S.A. New Concepts in Heparin-Induced Thrombocytopenia: Diagnosis and Management. J Thromb Thrombolysis 21, 17–21 (2006). https://doi.org/10.1007/s11239-006-5571-z

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  • DOI: https://doi.org/10.1007/s11239-006-5571-z

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