Abstract
We retrospectively evaluated dosing patterns and 37-day outcomes in argatroban-treated African American (n = 52), Asian (n = 13), and Hispanic (n = 14) patients with heparin-induced thrombocytopenia (HIT). The Asians required a lesser median dose (1.0 μg/kg/min) than the other groups (1.9 μg/kg/min, each) to achieve comparable activated partial thromboplastin times (medians: 61–69 s). Durations of therapy were similar (medians: 4.0–5.5 days). New thrombosis occurred in 11 (21%) African Americans, 1 (8%) Asian, and 1 (7%) Hispanic; of these 13 patients, 9 (69%) had baseline HIT-related thrombosis. Amputation occurred in 6 (12%) African Americans and 3 (21%) Hispanics; of these nine patients, 6 (67%) had diabetes. One (2%) African American and 1 (7%) Hispanic died from thrombosis. The composite of death due to thrombosis, amputation due to ischemic complications of HIT, or new thrombosis occurred in 14 (27%) African Americans, 1 (8%) Asian, and 4 (29%) Hispanics. Two (4%) African Americans and none others (0%) had major bleeding. These findings suggest that despite argatroban anticoagulation, African Americans and Hispanics may have worse outcomes in HIT than Asians. In minority patients with adverse HIT outcomes, baseline HIT-related thrombosis or diabetes is often present.
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Jang IK, Hursting MJ (2005) When heparin promote thrombosis: review of heparin-induced thrombocytopenia. Circulation 111:2671–2683. doi:10.1161/CIRCULATIONAHA.104.518563
Warkentin TE, Greinacher A, Koster A et al (2008) Treatment and prevention of heparin-induced thrombocytopenia. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 133:340S–380S. doi:10.1378/chest.08-0677
Kelton JG (2005) The pathophysiology of heparin-induced thrombocytopenia. Biological basis for treatment. Chest 127:S9–S20. doi:10.1378/chest.127.2_suppl.9S
Hirsh J, Heddle N, Kelton JG (2004) Treatment of heparin-induced thrombocytopenia: a critical review. Arch Intern Med 164:361–369. doi:10.1001/archinte.164.4.361
Lewis BE, Wallis DE, Hursting MJ et al (2006) Effects of argatroban therapy, demographic variables, and platelet count on thrombotic risks in heparin-induced thrombocytopenia. Chest 129:1407–1416. doi:10.1378/chest.129.6.1407
Keeling D, Davidson S, Watson H (2006) The management of heparin-induced thrombocytopenia. Br J Haematol 133:259–269. doi:10.1111/j.1365-2141.2006.06018.x
Rice LR, Hursting MJ (2008) Argatroban therapy for heparin-induced thrombocytopenia. Expert Rev Clin Pharm 1:357–367. doi:10.1586/17512433.1.3.357
Lewis BE, Wallis DE, Berkowitz SD et al (2001) Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation 103:1838–1843
Lewis BE, Wallis DE, Leya F et al (2003) Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med 163:1849–1856. doi:10.1001/archinte.163.15.1849
Greinacher A, Völpel H, Janssens U et al (1999) Recombinant hirudin (lepirudin) provides safe and effective anticoagulation in patients with heparin-induced thrombocytopenia: A prospective study. Circulation 99:73–80
Greinacher A, Janssens U, Berg G et al (1999) Lepirudin (recombinant hirudin) for parenteral anticoagulation in patients with heparin-induced thrombocytopenia. Circulation 100:587–593
Lubenow N, Eichler P, Lietz T et al (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. doi:10.1111/j.1538-7836.2005.01623.x
Chong BH, Gallus AS, Cade JF et al (2001) Prospective randomized open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopenia with thrombosis. Thromb Haemost 86:1170–1175
Magnani HN, 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. Thromb Haemost 95:967–981
Oliveira GBF, Crespo EM, Becker RC et al (2008) Incidence and prognostic significance of thrombocytopenia in patients treated with prolonged heparin therapy. Arch Intern Med 168:94–102. doi:10.1001/archinternmed.2007.65
Jang IK, Baron SJ, Hursting MJ et al (2007) Heparin-induced thrombocytopenia and argatroban therapy in women. J Womens Health 16:895–901. doi:10.1089/jwh.2006.0167
Rice L, Hursting MJ, Baillie GM et al (2007) Argatroban anticoagulation in obese versus nonobese patients: implications for treating heparin-induced thrombocytopenia. J Clin Pharmacol 47:1028–1034. doi:10.1177/0091270007302951
Shapiro NL, Durr EA, Krueger CD (2006) Prolonged anticoagulation after discontinuation of argatroban and warfarin therapy in an obese patient with heparin-induced thrombocytopenia. Pharmacotherapy 26:1806–1810. doi:10.1592/phco.26.12.1806
Reichert MG, MacGregor DA, Kincaid EH et al (2003) Excessive argatroban anticoagulation for heparin-induced thrombocytopenia. Ann Pharmacother 37:652–654. doi:10.1345/aph.1C187
Dang CH, Durkalski VL, Nappi JM (2006) Evaluation of treatment with direct thrombin inhibitors in patients with heparin-induced thrombocytopenia. Pharmacotherapy 26:461–468. doi:10.1592/phco.26.4.461
Williamson DR, Boulanger I, Tardif M et al (2004) Argatroban dosing in intensive care patients with acute renal failure and liver dysfunction. Pharmacotherapy 24:409–414. doi:10.1592/phco.24.4.409.33168
Cormack GM, Kaufman LJ (2007) Severe heparin-induced thrombocytopenia: when the obvious is not obvious, a case report. J Med Case Reports 1:13. doi:10.1186/1752-1947-1-13
Dager WE, White RH (2003) Argatroban for heparin-induced thrombocytopenia in hepato-renal failure and CVVHD. Ann Pharmacother 37:1232–1236. doi:10.1345/aph.1D010
Dager WE, White RH (2001) Use of lepirudin in patients with heparin-induced thrombocytopenia and renal failure requiring hemodialysis. Ann Pharmacother 35:885–890. doi:10.1345/aph.10282
Hayashi T, Suyama Y, Kaneko M et al (2004) Heparin-induced thrombocytopenia and thrombosis in a patient with polycythemia vera. Intern Med 43:587–597. doi:10.2169/internalmedicine.43.587
Alving BM (2003) How I treat heparin-induced thrombocytopenia and thrombosis. Blood 101:31–37. doi:10.1182/blood-2002-04-1089
Fabris F, Luzzatto G, Soini B et al (2002) Risk factors for thrombosis in patients with immune mediated heparin-induced thrombocytopenia. J Intern Med 252:149–154. doi:10.1046/j.1365-2796.2002.01021.x
Greinacher A, Farner B, Kroll H et al (2005) Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis. Thromb Haemost 94:132–135
Zwicker JI, Uhl L, Huang WY et al (2004) Thrombosis and ELISA optical density values in hospitalized patients with heparin-induced thrombocytopenia. J Thromb Haemost 2:2133–2137. doi:10.1111/j.1538-7836.2004.01039.x
Hong AP, Cook DJ, Sigouin CS et al (2003) Central venous catheters and upper-extremity deep-vein thrombosis complicating immune heparin-induced thrombocytopenia. Blood 101:3049–3051. doi:10.1182/blood-2002-05-1448
Carlsson LE, Lubenow N, Blumentritt C et al (2003) Platelet receptor and clotting factor polymorphisms as genetic risk factors for thromboembolic complications in heparin-induced thrombocytopenia. Pharmacogenetics 13:253–258. doi:10.1097/00008571-200305000-00003
LaMonte MP, Brown PM, Hursting MJ (2004) Stroke in patients with heparin-induced thrombocytopenia and the effect of argatroban therapy. Crit Care Med 32:976–980. doi:10.1097/01.CCM.0000119426.34340.E2
Carlsson LE, Santoso S, Baurichter G et al (1998) Heparin-induced thrombocytopenia: new insights into the impact of the FcgammaRIIa-R-H131 polymorphism. Blood 92:1526–1531
Harris K, Nguyen P, Van Cott EM (2008) Platelet PIA2 polymorphism and the risk for thrombosis in heparin-induced thrombocytopenia. Am J Clin Pathol 129:282–286. doi:10.1309/BMW4M8NQBV0TKFRX
Sykes TCF, Fegan C, Mosquera D (2005) Thrombophila, polymorphisms, and vascular disease. J Clin Pathol Mol Pathol 53:300–306
Albert MA (2007) Inflammatory biomarkers, race/ethnicity and cardiovascular disease. Nutr Rev 65:S234–S238. doi:10.1301/nr.2007.dec.S234-S238
Mensah GA, Mokdad AH, Ford ES et al (2005) State of disparities in cardiovascular health in the United States. Circulation 111:1233–1241. doi:10.1161/01.CIR.0000158136.76824.04
Kurian AK, Cardarelli KM (2007) Racial and ethnic differences in cardiovascular disease risk factors: a systematic review. Ethn Dis 17:143–152
Swan SK, Hursting MJ (2000) The pharmacokinetics and pharmacodynamics of argatroban: effects of age, gender, and hepatic or renal dysfunction. Pharmacotherapy 20:318–329. doi:10.1592/phco.20.4.318.34881
Levine R, Hursting MJ, McCollum D (2006) Argatroban therapy in heparin-induced thrombocytopenia with hepatic dysfunction. Chest 129:1167–1175. doi:10.1378/chest.129.5.1167
Hoffman WD, Czyz Y, McCollum D et al (2008) Reduced argatroban dosing after coronary artery bypass graft surgery. Ann Pharmacother 42:309–316. doi:10.1345/aph.1K434
Jang IK, Lewis BE, Matthai WH et al (2004) Argatroban anticoagulation in conjunction with glycoprotein IIb/IIIa inhibition in patients undergoing percutaneous coronary intervention: an open-label nonrandomized pilot study. J Thromb Thrombolysis 18:31–37. doi:10.1007/s11239-004-0171-2
Cox DS, Kleiman NS, Boyle DA et al (2004) Pharmacokinetics and pharmacodynamics of argatroban in combination with a platelet glycoprotein IIb/IIIa receptor antagonist in patients undergoing percutaneous coronary intervention. J Clin Pharmacol 44:981–990. doi:10.1177/0091270004267651
Gold HK, Torres FW, Garabedien HD et al (1993) Evidence for a rebound coagulation phenomenon after cessation of a 4-hour infusion of a specific thrombin inhbitor in patients with unstable angina pectoris. J Am Coll Cardiol 21:1039–1047
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MJH received consultancy fees from GlaxoSmithKline. IKJ has received grant support from GlaxoSmithKline. The authors have full control of all primary data and agree to allow the journal to review their data, if requested.
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Hursting, M.J., Jang, IK. Dosing patterns and outcomes in African American, Asian, and Hispanic patients with heparin-induced thrombocytopenia treated with argatroban. J Thromb Thrombolysis 28, 10–15 (2009). https://doi.org/10.1007/s11239-008-0295-x
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DOI: https://doi.org/10.1007/s11239-008-0295-x