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Heparin-Induced Thrombocytopenia

  • Carmel A. Celestin
  • John R. Bartholomew
Part of the Biotechnology: Pharmaceutical Aspects book series (PHARMASP, volume VIII)

Abstract

Heparin-induced thrombocytopenia (HIT) is a devastating complication of either unfractionated heparin or any of the low molecular weight heparin (LMWH) preparations. This immune-mediated process generally develops within 5–14 days of administration, although it may occur more rapidly if there has been a recent exposure, or even days to weeks after either preparation has been discontinued. Although once considered necessary for the diagnosis of HIT, thrombocytopenia is no longer essential. A 50 reduction in the platelet count from pre-heparin treatment levels is now considered a more specific finding. Immediate cessation of heparin or LMWH is recommended once the diagnosis is suspected and alternative therapy with a non-heparin anticoagulant advised due to the potential for new thrombosis, amputation or even death.

Keywords

International Normalize Ratio Disseminate Intravascular Coagulation Unfractionated Heparin Activate Clotting Time Direct Thrombin Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Amin, D. M., Mant, T. G., Walker, S. M., Kerry, R., Lloyd, P., Lefevre, G., and Close, P. 1997. Effect of a 15-minute infusion of DDAVP on the pharmacokinetics and pharmacodynamics of REVASC during a four-hour intravenous infusion in healthy male volunteers. J. Thromb. Haemost. 77:127–132.Google Scholar
  2. Amiral, J., Wolf, M., Fischer, A., Boyer-Neumann, C., Vissac, A., and Meyer, D. 1996. Pathogenicity of IgA and/or IgM antibodies to heparin-PF4 complexes in patients with heparin-induced thrombocytopenia. Br. J. Haematol. 92:954–959.PubMedGoogle Scholar
  3. Amiral, J., Pouplard, C., Vissac, A. M., Walenga, J. M., Jeske, W., and Gruel, Y. 2000. Affinity purification of heparin-dependent antibodies to platelet factor 4 developed in heparin-induced thrombocytopenia: biological characteristics and effects on platelet activation. Br. J. Haematol. 109:336–341.PubMedGoogle Scholar
  4. Ancalmo, N., and Ochsner, J. 1990. Heparin, the miracle drug: a brief history of its discovery. J. La. State Med. Soc. 142:22–24.PubMedGoogle Scholar
  5. Antonijevic, N. M., Savic, N. B., Perunicic, J., Kovac, M., Mikovic, D., Stanojevic, M., Calija, B., Milosevic, R. A., Obradovic, S. D., and Vasiljevic, Z. 2006. Salvage late plasmapheresis in a patient with pulmonary embolism caused by heparin-induced thrombocytopenia primarily resistant to danaparoid sodium and lepirudin. J. Clin. Apher. 21:252–255.PubMedGoogle Scholar
  6. Arpino, P. A., Demirjian, Z., and Van Cott, E. M. 2005. Use of the chromogenic factor X assay to predict the international normalized ratio in patients transitioning from argatroban to warfarin. Pharmacotherapy 25:157–164.PubMedGoogle Scholar
  7. Barrit, D. W., and Jordan, S. C. 1960. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet 1:1309–1312.Google Scholar
  8. Bartholomew, J. R., Begelman, S. M., and Almahameed, A. 2005a. Heparin-induced thrombocytopenia: principles for early recognition and management. Cleve. Clin. J. Med. 72 (Suppl 1):S31–36.Google Scholar
  9. Bartholomew, J. R., and Hursting, M. J. 2005b. Transitioning from argatroban to warfarin in heparin-induced thrombocytopenia: an analysis of outcomes in patients with elevated international normalized ratio (INR). J. Thromb. Thrombolysis 19:183–188.Google Scholar
  10. Bauer, K. A., Eriksson, B. I., Lassen, M. R., and Turpie, A. G. 2001. Steering Committee of the Pentasaccharide in Major Knee Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N. Engl. J. Med. 345:1305–1310.PubMedGoogle Scholar
  11. Beiderlinden, M., Treschan, T. A., Gorlinger, K., and Peters, J. 2007. Argatroban anticoagulation in critically ill patients. Ann. Pharmacother. 41:749–754.PubMedGoogle Scholar
  12. Berilgen, J. E., Nguyen, P. H., Baker, K. R., and Rice, L. 2003. Bivalirudin treatment of heparin-induced thrombocytopenia [abstr]. Blood 102:537a.Google Scholar
  13. Berkowitz, S.D. 1999. Antigenic potential of bivalirudin [abstr]. Blood 94 (suppl 1):102.Google Scholar
  14. Berry, C. N., Girardot, C., Lecoffre, C., and Lunven, C. 1994. Effects of the synthetic thrombin inhibitor argatroban on fibrin- or clot-incorporated thrombin: comparison with heparin and recombinant Hirudin. Thromb. Haemost. 72:381–386.PubMedGoogle Scholar
  15. Bjork, I., Olson, S. T., and Shore, J. D. 1989. Molecular mechanisms of the accelerating effect of heparin on the reactions. between antithrombin and clottingproteinases. In Lane, D. A., and Lindhal, U. (eds.), Heparin. Clinical and biological properties clinical application, Boca Raton, Fla, CRC Press.Google Scholar
  16. Bufton, M. G., et al. 2002. Bivalirudin effect on the INR and experience with prolonged inpatient and outpatient anticoagulation with bivalirudin for treatment of leg ischemia and arterial thrombosis due to HIT-TS (abstr). Blood 100:124b.Google Scholar
  17. Buller, H. R., Davidson, B. L., Decousus, H., Gallus, A., Gent, M., Piovella, F., Prins, M. H., Raskob, G., Segers, A. E. M., Cariou, R., Leeuwenkamp, O., and Lensing, A. W. A. 2004. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann. Intern. Med. 140:867–873.PubMedGoogle Scholar
  18. Buller, H. R., Davidson, B. L., Decousus, H., Gallus, A., Gent, M., Piovella, F., Prins, M. H., Raskob, G., van den Berg-Segers, A. E. M., Cariou, R., Leeuwenkamp, O., and Lensing, A. W. A. 2003. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N. Engl. J. Med. 349:1695–1702.PubMedGoogle Scholar
  19. Campbell, K. R., Mahaffey, K. W., Lewis, B. E., Weitz, J. I., Berkowitz, S. D., Ohman, E. M., and Califf, M. 2000. Bivalirudin in patients with heparin-induced thrombocytopenia undergoing percutaneous coronary intervention. J. Invasive Cardiol. 12 (Suppl F):14F–19F.PubMedGoogle Scholar
  20. Cardenas, G. A., and Deitcher, S. R. 2005. Risk of anaphylaxis after reexposure to intravenous lepirudin in patients with current or past heparin-induced thrombocytopenia. Mayo Clin. Proc. 80:491–493.PubMedGoogle Scholar
  21. Chong, B. H., Fawaz, I., Chesterman, C. N., and Berndt, M. C. 1989. Heparin-induced thrombocytopenia: mechanism of interaction of the heparin-dependent antibody with platelets. Br. J. Haematol. 73:235–240.PubMedGoogle Scholar
  22. Chong, B. H. 2003. Heparin-induced thrombocytopenia. J. Thromb. Haemost. 1:1471–1478.PubMedGoogle Scholar
  23. Chong, B. H., Gallus, A. S., Cade, J. F., Magnani, H., Manoharan, A., Oldmeadow, M., Arthur, C., Richard, K., Gallo, J, Lloyd, J., Seshadri, P., and Chesterman, N. 2001 Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study. J. Thromb. Haemost. 86:1170–1175.Google Scholar
  24. Cimo, P. L., Moake, J. L., Weinger, R. S., Ben-Menachem, Y. B., and Khalil, K. G. 1979. Heparin-induced thrombocytopenia: association with a platelet aggregating factor and arterial thromboses. Am. J. Hematol. 6:125–133.PubMedGoogle Scholar
  25. Cosmi, B., Fredenburgh, J. C., Rischke, J., Hirsh, J., Young, E., and Weitz, J. I. 1997. Effect of nonspecific binding to plasma proteins on the antithrombin activities of unfractionated heparin, low-molecular-weight heparin, and dermatan sulfate. Circulation 95:118–124.PubMedGoogle Scholar
  26. Cruickshank, M. K., Levine, M. N., Hirsh, J., Roberts, R., and Siguenza, M. 1991. A standard heparin nomogram for the management of heparin therapy. Arch. Intern. Med. 151:333–337.PubMedGoogle Scholar
  27. Danielsson, A., and Bjork, I. 1981. Binding to antithrombin of heparin fractions with different molecular weights. Biochem. J. 193:427–433.PubMedGoogle Scholar
  28. Dyke, C. M., Koster, A., Veale, J. J., Maier, G. W., McNiff, T., and Levy, J. H. 2005. Preemptive use of bivalirudin for urgent on-pump coronary artery bypass grafting in patients with potential heparin-induced thrombocytopenia. Ann. Thorac. Surg. 80:299–303.PubMedGoogle Scholar
  29. Dyke, C. M., Smedira, N. G., Koster, A., Aronson, S., McCarthy, H. L., Kirshner, R., Lincoff, A. M., and Spiess, B. D. 2006. A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass: The EVOLUTION-ON study. J. Thorac. Cardiovasc. Surg. 131:533–539.PubMedGoogle Scholar
  30. Efird, L. E., and Kockler, D. R. 2006. Fondaparinux for thromboembolic treatment and prophylaxis of heparin-induced thrombocytopenia. Ann. Pharmacother. 40:1383–1387.PubMedGoogle Scholar
  31. Eichler, P., Raschke, R., Lubenow, N., Meyer, O., Schwind, P., and 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. 116:887–891.PubMedGoogle Scholar
  32. Eichler, P., Lubenow, N., Strobel, U., and Greinacher, A. 2004. Antibodies against lepirudin are polyspecific and recognize epitopes on bivalirudin. Blood 103:613–616.PubMedGoogle Scholar
  33. Eichler, P., Friesen, H. J., Lubenow, N., Jaeger, B., and Greinacher, A. 2000. Antihirudin antibodies in patients with heparin-induced thrombocytopenia treated with lepirudin: Incidence, effects on aPTT, and clinical relevance. Blood 96:2373–2378.PubMedGoogle Scholar
  34. Fabris, F., Luzzatto, G., Soini, B., Ramon, R., Scandellari, R., Randi, M. L., and Girolami, A. 2002. Risk factors for thrombosis in patients with immune mediated heparin-induced thrombocytopenia. J. Intern. Med. 252:149–154.PubMedGoogle Scholar
  35. Fareed, J., Walenga, J. M., Hoppensteadt, D., Huan, X., and Racanelli, A. 1988. Comparative study on the in vitro and in vivo activities of seven low-molecular-weight heparins. Haemostasis 18 (Suppl 3):3–15.PubMedGoogle Scholar
  36. Farner, B., Eichler, P., Kroll, H., and Greinacher, A. 2001. A comparison of danaparoid and lepirudin in heparin-induced thrombocytopenia. J. Thromb. Haemost. 85:950–957.Google Scholar
  37. Fausett, M. B., Vogtlander, M., Lee, R. M., Esplin, M. S., Branch, D. W., Rodgers, G. M., and Silver, R. M. 2001. Heparin-induced thrombocytopenia is rare in pregnancy. Am. J. Obstet. Gynecol. 185:148–152.PubMedGoogle Scholar
  38. Frame, J. N., Mulvey, K. P., Phares, J. C., and Anderson, M. J. 1989. Correction of severe heparin-associated thrombocytopenia with intravenous immunoglobulin. Ann. Intern. Med. 111:946–947.PubMedGoogle Scholar
  39. Ganzer, D., Gutezeit, A., and Mayer, G. 1999. Potentials risks in drug prevention of thrombosis—low-molecular-weight heparin versus standard heparin. Z. Orthop. Ihre. Grenzgeb. 137:457–461.PubMedGoogle Scholar
  40. Geerts, W. H., Pineo, G. F., Heit, J. A., Bergqvist, D., Lassen, M. R., Colwell, C. W., and Ray, J. G. 2004. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126 (Suppl 3):338S–400S.Google Scholar
  41. Girolami, B., Prandoni, P., Stefani, P. M., Tanduo, C., Sabbion, P., Eichler, P., Ramon, R., Baggio, G., Fabris, F., and Girolami, A. 2003. The incidence of heparin-induced thrombocytopenia in hospitalized medical patients treated with subcutaneous unfractionated heparin: a prospective cohort study. Blood 101:2955–2959.PubMedGoogle Scholar
  42. Gosselin, R. C., Dager, W. E., King, J. H., Janatpour, K., Mahackian, K., Larkin, E. C., and Owings, E. T. 2004. Effect of direct thrombin inhibitors, bivalirudin, lepirudin, and argatroban, on prothrombin time and INR values. Am. J. Clin. Pathol. 121:593–599.PubMedGoogle Scholar
  43. Greinacher, A., Gopinadhan, M., Gunther, J. U., Omer-Adam, M. A., Strobel, U., Warkentin, T. E., Papastravou, G. Weitschies, W., and Helm, C. A. 2006. Close approximation of two platelet factor 4 tetramers by charge neutralization forms the antigens recognized by HIT antibodies. Arterioscler. Thromb. Vasc. Biol. 26:2386–2393.Google Scholar
  44. Greinacher, A., Eichler, P., Lubenow, N., Kwasny, H., and 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 96:846–851.PubMedGoogle Scholar
  45. Greinacher, A., Farner, B., Kroll, H., Kohlmann, T., Warkentin, T. E., and Eichler, P. 2005. Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis. A retrospective analysis of 408 patients. J. Thromb. Haemost. 94:132–135.Google Scholar
  46. Greinacher, A., Eichler, P., Albrecht, D., Strobel, U., Potzsch, B., and Eriksson, B. I. 2003a. Antihirudin antibodies following low-dose subcutaneous treatment with desirudin for thrombosis prophylaxis after hip-replacement surgery: incidence and clinical relevance. Blood 101:2617–2619.Google Scholar
  47. Greinacher, A., Lubenow, N., and Eichler, P. 2003b. Anaphylactic and anaphylactoid reactions associated with lepirudin in patients with heparin-induced thrombocytopenia. Circulation 108:2062–2065.Google Scholar
  48. Greinacher, A., and Warkentin, T. E. 2004. Treatment of heparin-induced thrombocytopenia: an overview. In Heparin-induced thrombocytopenia, 3rd edition. Marcel Dekker Inc, Basel, pp. 355–370.Google Scholar
  49. Herbert, J.-M., Petitou, M., and Lormeau, J.-C. 1997. SR90107A/Org31540, a novel anti-factor Xa antithrombotic agent. Cardiovasc. Drug Ref. 15:1–26.Google Scholar
  50. Hirsh, J., and Levine, M. N. 1992. Low molecular weight heparin. Blood 79:1–17.PubMedGoogle Scholar
  51. Hirsh, J., van Aken, W. G., Gallus, A. S., Dollery, C. T., Cade, J. F., and Yung, W. L. 1976. Heparin kinetics in venous thrombosis and pulmonary embolism. Circulation 53:691–695.PubMedGoogle Scholar
  52. Hirsh, J. 1991. Heparin. N. Engl. J. Med. 324:1565–1574.PubMedGoogle Scholar
  53. Hirsh, J., and Raschke, R. 2004a. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126(Suppl 3):188S–203S.Google Scholar
  54. Hirsh, J., Heddle, N., and Kelton, J. G. 2004b. Treatment of heparin-induced thrombocytopenia: a critical review. Arch. Intern. Med. 164:361–369.Google Scholar
  55. Ibbotson, S. H., Grant, P. J., Kerry, R., Findlay, V. S., and Prentice, C. R. 1991. The influence of infusions of 1-desamino-8-D-arginine vasopressin (DDAVP) in vivo on the anticoagulant effect of recombinant hirudin (CGP39393) in vitro. J. Thromb. Haemost. 65:64–66.Google Scholar
  56. Irani, M. S., White, H. J. Jr., Sexon, R. G. 1995. Reversal of hirudin-induced bleeding diathesis by prothrombin complex concentrate. Am. J. Cardiol. 75(5):422–423.PubMedGoogle Scholar
  57. Irvin, W., Sica, D., Gehr, T., McAllister, A., Rogge, M., Charenkavanich, S., and Adelman, B. 1999. Pharmacodynamics (PD) and kinetics (PK) of bivalirudin (BIV) in renal failure (RF) and hemodialysis (HD) [abstr]. Clin. Pharmacol. Ther. 65:202.Google Scholar
  58. Kaplan, K. L., and Francis, C. W. 2002. Direct thrombin inhibitors. Semin. Hematol. 39:187–196.PubMedGoogle Scholar
  59. Kappers-Klunne, M. C., Boon, D. M., Hop, W. C., Michiels, J. J., Stibbe, J., van der Zwaan, C., Koudstaal, P. J., and van Vliet, H. H. D. M. 1997. Heparin-induced thrombocytopenia and thrombosis: a prospective analysis of the incidence in patients with heart and cerebrovascular diseases. Br. J. Haematol. 96:442–446.PubMedGoogle Scholar
  60. Kearon, C., Ginsberg, J. S., Julian, J. A., Douketis, J., Solymoss, S., Ockelford, P., Jackson, S., Turpie, A. G., MacKinnon, B., Hirsh, J., and Gent, M. 2006. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA 296:935–942.PubMedGoogle Scholar
  61. Kearon, C., Johnston, M., Moffat, K., McGinnis, J., and Ginsberg, J. S. 1998. Effect of warfarin on activated partial thromboplastin time in patients receiving heparin. Arch. Intern. Med. 158:1140–1143.PubMedGoogle Scholar
  62. Klenner, A. F., Lubenow, N., Raschke, R., and Greinacher, A. 2004. Heparin-induced thrombocytopenia in children: 12 new cases and review of the literature. J. Thromb. Haemost. 91:719–724.Google Scholar
  63. Koster, A., Dyke, C. M., Aldea, G., Smedira, N. G., McCarthy, H. L., Aronson, S., Hetzer, R., Avery, E., Spiess, B., and Lincoff, A. M. 2007. Bivalirudin during cardiopulmonary bypass in patients with previous or acute heparin-induced thrombocytopenia and heparin antibodies: results of the CHOOSE-ON trial. Ann. Thorac. Surg. 83:572–577.PubMedGoogle Scholar
  64. Levy, J. H., and Hursting, M. J. 2007. Heparin-induced thrombocytopenia, a prothrombotic disease. Hematol. Oncol. Clin. North Am. 21:65–88.PubMedGoogle Scholar
  65. Lewis, B. E., Wallis, D. E., Berkowitz, S. D., Matthai, W. H., Fareed, J., Walenga, J. M., and Bartholomew, J. 2001. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation 103:1838–1843.PubMedGoogle Scholar
  66. Lewis, B. E., Wallis, D. E., Leya, F., Hursting, M. J., and Kelton, J. G. 2003. Argatroban-915 Investigators. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch. Intern. Med. 163:1849–1856.Google Scholar
  67. Lindhoff-Last, E., Nakov, R., Misselwitz, F., Breddin, H. K., and Bauersachs, R. 2002. Incidence and clinical relevance of heparin-induced antibodies in patients with deep vein thrombosis treated with unfractionated or low-molecular-weight heparin. Br. J. Haematol. 118:1137–1142.PubMedGoogle Scholar
  68. Linkins, L. A., and Weitz, J. I. 2005. Pharmacology and clinical potential of direct thrombin inhibitors. Curr. Pharm. Des. 11:3877–3884.PubMedGoogle Scholar
  69. Lo, G. K., Juhl, D., Warkentin, T. E., Sigouin, C. S., Eichler, P., and Greinacher, A. 2006. Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J. Thromb. Haemost. 4:759–765.PubMedGoogle Scholar
  70. Lubenow, N., Kempf, R., Eichner, A., Eichler, P., Carlsson, L. E., and Greinacher, A. 2002. Heparin-induced thrombocytopenia: temporal pattern of thrombocytopenia in relation to initial use or reexposure to heparin. Chest 122:37–42.PubMedGoogle Scholar
  71. Lubenow, N., Eichler, P., Lietz, T., and Greinacher, A, Hit Investigators Group. 2005. 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. 3:2428–2436.PubMedGoogle Scholar
  72. Luster, A. D. 1998. Chemokines—chemotactic cytokines that mediate inflammation. N. Engl. J. Med. 338:436–445.PubMedGoogle Scholar
  73. Magnani, H. N., and Gallus, A. 2006. Heparin-induced thrombocytopenia (HIT). A report of 1,478 clinical outcomes of patients treated with danaparoid (Orgaran) from 1982 to mid-2004. J. Thromb. Haemost. 95:967–981.Google Scholar
  74. Mahaffey, K. W., Lewis, B. E., Wildermann, N. M., Berkowitz, S. D., Oliverio, R. M., Turco, M. A., Shalev, Y., Ver Lee, P., Traverse, J. H., Rodriguez, A. R., Ohman, E. M., Harrington, R. A., and Califf, R. M. 2003. The anticoagulant therapy with bivalirudin to assist in the performance of percutaneous coronary intervention in patients with heparin-induced thrombocytopenia (ATBAT) study: main results. J. Invasive Cardiol. 15:611–616.PubMedGoogle Scholar
  75. Mahlfeld, K., Franke, J., Schaeper, O., Kayser, R., and Grasshoff, H. 2002. Heparin-induced thrombocytopenia as a complication of postoperative prevention of thromboembolism with unfractionated heparin/low molecular weight heparin after hip and knee prosthesis implantation. Unfallchirurg 105:327–331.PubMedGoogle Scholar
  76. Makhoul, R. G., McCann, R. L., Austin, E. H., Greenberg, C. S., and Lowe, J. E. 1987. Management of patients with heparin-associated thrombocytopenia and thrombosis requiring cardiac surgery. Ann. Thorac. Surg. 43:617–621.PubMedGoogle Scholar
  77. Marx, A., Huhle, G., Hoffmann, U., Wang, L. C., Schule, B., Jani, L., and Harenberg, J. 1999. Heparin-induced thrombocytopenia after elective hip joint replacement with postoperative prevention of thromboembolism with low-molecular-weight heparin. Z. Orthop. Ihre. Grenzgeb. 137:536–539.PubMedGoogle Scholar
  78. Merry, A. F., Raudkivi, P. J., Middleton, N. G., McDougall, J. M., Nand, P., Mills, B. P., Webber, B. J., Frampton, C. M., and White, H. D. 2004. Bivalirudin versus heparin and protamine in off-pump coronary artery bypass surgery. Ann. Thorac. Surg. 77:925–931; discussion 931.PubMedGoogle Scholar
  79. Mon, C., Moreno, G., Ortiz, M., Diaz, R., Herrero, J. C., Oliet, A., Rodriguez, I., Ortega, O., Gallar, P., and Vigil, A. 2006. Treatment of hirudin overdosage in a dialysis patient with heparin-induced thrombocytopenia with mixed hemodialysis and hemofiltration treatment. Clin. Nephrol. 66:302–305.PubMedGoogle Scholar
  80. Newman, P. M., Swanson, R. L., and Chong, B. H. 1998. Heparin-induced thrombocytopenia: IgG binding to PF4-heparin complexes in the fluid phase and cross-reactivity with low molecular weight heparin and heparinoid. J. Thromb. Haemost. 80:292–297.Google Scholar
  81. Olinger, G. N., Hussey, C. V., Olive, J. A., and Malik, M. I. 1984. Cardiopulmonary bypass for patients with previously documented heparin-induced platelet aggregation. J. Thorac. Cardiovasc. Surg. 87:673–677.PubMedGoogle Scholar
  82. Opatrny, L., and Warner, M. N. 2004. Risk of thrombosis in patients with malignancy and heparin-induced thrombocytopenia. Am. J. Hematol. 76:240–244.PubMedGoogle Scholar
  83. Oppenheim, J. J., Zachariae, C. O., Mukaida, N., and Matsushima, K. 1991. Properties of the novel proinflammatory supergene “intercrine” cytokine family. Annu. Rev. Immunol. 9:617–648.PubMedGoogle Scholar
  84. Potzsch, B., Klovekorn, W. P., and Madlener, K. 2000. Use of heparin during cardiopulmonary bypass in patients with a history of heparin-induced thrombocytopenia. N. Engl. J. Med. 343:515.PubMedGoogle Scholar
  85. Pouplard, C., May, M. A., Regina, S., Marchand, M., Fusciardi, J., and Gruel, Y. 2005. Changes in platelet count after cardiac surgery can effectively predict the development of pathogenic heparin-dependent antibodies. Br. J. Haematol. 128:837–841.PubMedGoogle Scholar
  86. Prandoni, P., Siragusa, S., Girolami, B., and Fabris, F., BELZONI Investigators Group. 2005. The incidence of heparin-induced thrombocytopenia in medical patients treated with low-molecular-weight heparin: a prospective cohort study. Blood 106:3049–3054.PubMedGoogle Scholar
  87. Ramirez, L. M., Carman, T. L., Begelman, S. M., AlMahameed, A., Joseph, D., Kashyap, V., White, D. A., Andersen-Harris, K., and Bartholomew, J. R. 2005. Bivalirudin in patients with clinically suspected HIT or history of HIT [abstr]. Blood 106:269a.Google Scholar
  88. Raschke, R. A., Reilly, B. M., Guidry, J. R., Fontana, J. R., and Srinivas, S. 1993. The weight-based heparin dosing nomogram compared with a “standard care” nomogram. A randomized controlled trial. Ann. Intern. Med. 119:874–881.Google Scholar
  89. Reed, M. D. and Bell, D. 2002. Clinical pharmacology of bivalirudin. Pharmacotherapy 22(6 Pt 2):105S–111S.Google Scholar
  90. Rhodes, G. R., Dixon, R. H., and Silver, D. 1973. Heparin induced thrombocytopenia with thrombotic and hemorrhagic manifestations. Surg. Gynecol. Obstet. 136:409–416.PubMedGoogle Scholar
  91. Rhodes, G. R., Dixon, R. H., and Silver, D. 1977. Heparin induced thrombocytopenia: eight cases with thrombotic-hemorrhagic complications. Ann. Surg. 186:752–758.PubMedGoogle Scholar
  92. Robinson, J. A., and Lewis, B. E. 1999. Plasmapheresis in the management of heparin-induced thrombocytopenia. Semin. Hematol. 36(Suppl 1):29–32.PubMedGoogle Scholar
  93. Robson, R. 2000. The use of bivalirudin in patients with renal impairment. J. Invasive Cardiol. 12 (Suppl F):33F–36F.PubMedGoogle Scholar
  94. Robson, R., White, H., Aylward, P., and Frampton, C. 2002. Bivalirudin pharmacokinetics and pharmacodynamics: effect of renal function, dose, and gender. Clin. Pharmacol. Ther. 71:433–439.PubMedGoogle Scholar
  95. Rollins, B. J. 1997. Chemokines. Blood 90:909–928.PubMedGoogle Scholar
  96. Ross, B. P., and Toth, I. 2005 Gastrointestinal absorption of heparin by lipidization or coadministration with penetration enhancers. Current Drug Delivery. 2:277–287.PubMedGoogle Scholar
  97. Savi, P., Chong, B. H., Greinacher, A., Gruel, Y., Kelton, J. G., Warkentin, T. E., Eichler, P., Meuleman, D., Petitou, M., Herault, J.-P., Cariou, R., and Herbert, J.-M. 2005. Effect of fondaparinux on platelet activation in the presence of heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin. Blood 105:139–144.PubMedGoogle Scholar
  98. Sciulli, T. M. and Mauro, V. F. 2002. Pharmacology and clinical use of bivalirudin. Ann. Pharmacother. 36:1028–1041.Google Scholar
  99. Selleng, S., Lubenow, N., Wollert, H. G., Mullejans, B., and Greinacher, A. 2001. Emergency cardiopulmonary bypass in a bilaterally nephrectomized patient with a history of heparin-induced thrombocytopenia: successful reexposure to heparin. Ann. Thorac. Surg. 71:1041–1042.PubMedGoogle Scholar
  100. Sheridan, D., Carter, C., and Kelton, J. G. 1986. A diagnostic test for heparin-induced thrombocytopenia. Blood 67:27–30.PubMedGoogle Scholar
  101. Sheth, S. B., DiCicco, R. A., Hursting, M. J., Montague, T., and Jorkasky, D. K. 2001. Interpreting the International Normalized Ratio (INR) in individuals receiving argatroban and warfarin. J. Thromb. Haemost. 85:435–440.Google Scholar
  102. Shuster, T. A., Silliman, W. R., Coats, R. D., Mureebe, L., and Silver, D. 2003. Heparin-induced thrombocytopenia: twenty-nine years later. J. Vasc. Surg. 38:1316–1322.PubMedGoogle Scholar
  103. Smedira, N. G., Dyke, C. M., Koster, A., Jurmann, M., Bhatia, D. S., Hu, T., McCarthy, H. L., Lincoff, A. M., Spiess, B. D., and Aronson, S. 2006. Anticoagulation with bivalirudin for off-pump coronary artery bypass grafting: the results of the EVOLUTION-OFF study. J. Thorac. Cardiovasc. Surg. 131:686–692.PubMedGoogle Scholar
  104. Smythe, M. A., Stephens, J. L., Koerber, J. M., and Mattson, J. C. 2005. A comparison of lepirudin and argatroban outcomes. Clin. Appl. Thromb. Hemost. 11:371–374.PubMedGoogle Scholar
  105. Spinler, S. A. 2006. New concepts in heparin-induced thrombocytopenia: diagnosis and management. J. Thromb. Thrombolysis 21:17–21.PubMedGoogle Scholar
  106. Srinivasan, A. F., Rice, L., Bartholomew, J. R., Rangaswamy, C., La Perna, L., Thompson, J. E., Murphy, S., and Baker, K. R. 2004. Warfarin-induced skin necrosis and venous limb gangrene in the setting of heparin-induced thrombocytopenia. Arch. Intern. Med. 164:66–70.PubMedGoogle Scholar
  107. Trask, A. S., Gosselin, R. C., Diaz, J. A., and Dager, W. E. 2004. Warfarin initiation and monitoring with clotting factors II, VII, and X. Ann. Pharmacother. 38:251–256.PubMedGoogle Scholar
  108. Turpie, A. G., Bauer, K. A., Eriksson, B. I., and Lassen, M. R., PENTATHALON 2000 Study Steering Committee. 2002. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet 359:1721–1726.Google Scholar
  109. Walenga, J. M., Jeske, W. P., Prechel, M. M., Bacher, P., and Bakhos, M. 2004. Decreased prevalence of heparin-induced thrombocytopenia with low-molecular-weight heparin and related drugs. Semin. Thromb. Hemost. 30 (Suppl 1):69–80.PubMedGoogle Scholar
  110. Wallis, D. E., Workman, D. L., Lewis, B. E., Steen, L., Pifarre, R., and Moran, J. F. 1999 Failure of early heparin cessation as treatment for heparin-induced thrombocytopenia. Am. J. Med. 106:629–635.PubMedGoogle Scholar
  111. Warkentin, T. E., Hayward, C. P., Boshkov, L. K., Santos, A. V., Sheppard, J. A., Bode, A. P., and Kelton J. G. 1994. Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia. Blood 84:3691–3699.PubMedGoogle Scholar
  112. Warkentin, T. E. and Kelton, J. G. 2001. Temporal aspects of heparin-induced thrombocytopenia. N. Engl. J. Med. 344:1286–1292.PubMedGoogle Scholar
  113. Warkentin, T. E. and Greinacher, A. 2004. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126(Suppl 3):311S–337S.PubMedGoogle Scholar
  114. Warkentin, T. E., Sheppard, J. A., Horsewood, P., Simpson, P. J., Moore, J. C., and Kelton, J. G. 2000. Impact of the patient population on the risk for heparin-induced thrombocytopenia. Blood 96:1703–1708.PubMedGoogle Scholar
  115. Warkentin, T. E., Levine, M. N., Hirsh, J., Horsewood, P., Roberts, R. S., Gent, M., and Kelton, J. G. 1995. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N. Engl. J. Med. 332:1330–1335.PubMedGoogle Scholar
  116. Warkentin, T. E. and Kelton, J. G. 1996. A 14-year study of heparin-induced thrombocytopenia. Am. J. Med. 101:502–507.PubMedGoogle Scholar
  117. Warkentin, T. E. 1999. Heparin-induced thrombocytopenia: a clinicopathologic syndrome. J. Thromb. Haemost. 82:439–447.Google Scholar
  118. Warkentin, T. E. 2003a. Heparin-induced thrombocytopenia: pathogenesis and management. Br. J. Haematol. 121:535–555.Google Scholar
  119. Warkentin, T. E. and Heddle, N. M. 2003b. Laboratory diagnosis of immune heparin-induced thrombocytopenia. Curr. Hematol. Rep. 2:148–157.Google Scholar
  120. Warkentin, T. E. 2005a. New approaches to the diagnosis of heparin-induced thrombocytopenia. Chest 127(Suppl 2):35S–45S.Google Scholar
  121. Warkentin, T. E., Cook, R. J., Marder, V. J., Sheppard, J. A., Moore, J. C., Eriksson, B. I., Greinacher, A., and Kelton, J. G. 2005b. Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin. Blood 106:3791–3796.Google Scholar
  122. Warkentin, T. E., Greinacher, A., Craven, S., Dewar, L., Sheppard, J. A., and Ofosu, F. A. 2005c. Differences in the clinically effective molar concentrations of four direct thrombin inhibitors explain their variable prothrombin time prolongation. J. Thromb. Haemost. 94:958–964.Google Scholar
  123. Warkentin, T. E., Maurer, B. T., and Aster, R. H. 2007. Heparin-induced thrombocytopenia associated with fondaparinux. N. Engl. J. Med. 356:2653–2655.PubMedGoogle Scholar
  124. Weisman, R. E. and Tobin, R. W. 1958. Arterial embolism occurring during systemic heparin therapy. Arch. Surg. 76:219–225; discussion 225–227.Google Scholar
  125. Winder, A., Shoenfeld, Y., Hochman, R., Keren, G., Levy, Y., and Eldor, A. 1998. High-dose intravenous gamma-globulins for heparin-induced thrombocytopenia: a prompt response. J. Clin. Immunol. 18:330–334.PubMedGoogle Scholar
  126. Yeh, R. W. and Jang, I. K. 2006. Argatroban: update. Am. Heart J. 151:1131–1138.PubMedGoogle Scholar
  127. Young, E., Cosmi, B., Weitz, J., and Hirsh, J. 1993. Comparison of the non-specific binding of unfractionated heparin and low molecular weight heparin (Enoxaparin) to plasma proteins. J. Thromb. Haemost. 70:625–630.Google Scholar
  128. Yusuf, S., Mehta, S. R., Chrolavicius, S., Afzal, R., Pogue, J., Granger, C. B., Budaj, A, Peters, R. J., Bassand, J. P., Wallentin, L., Joyner, C., and Fox, K. A. 2006a. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA 295:1519–1530.Google Scholar
  129. Yusuf, S., Mehta, S. R., Chrolavicius, S., Afzal, R., Pogue, J., Granger, C. B., Budaj, A, Peters, R. J., Bassand, J. P., Wallentin, L., Joyner, C., and Fox, K. A. 2006b. Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators, Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N. Engl. J. Med. 354:1464–1476.Google Scholar

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© American Association of Pharmaceutical Scientists 2008

Authors and Affiliations

  • Carmel A. Celestin
  • John R. Bartholomew

There are no affiliations available

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