Heparin Induced Thrombocytopenia – Pathophysiology, Diagnosis and Treatment: A Narrative Review

References

• Ahmed I, Majeed A, Powell R. Heparin induced thrombocytopenia: diagnosis and management update. Postgrad Med J. 2007;83(983):575–582. doi:10.1136/pgmj.2007.059188
   PubMed Web of Science ®Google Scholar
• Greinacher A, Farner B, Kroll H, Kohlmann T, Warkentin TE, Eichler P. Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis. A retrospective of 408 patients. Thromb Haemost. 2005;94(1):132–135. doi:10.1160/TH04-12-0825
   PubMed Web of Science ®Google Scholar
• Warkentin TE, Maurer BT, Aster RH. Heparin-induced thrombocytopenia associated with fondaparinux. N Engl J Med. 2007;356(25):2653–2655. doi:10.1056/NEJMc070346
   PubMed Web of Science ®Google Scholar
• Franchini M. Heparin-induced thrombocytopenia: an update. Thromb J. 2005;3:14. doi:10.1186/1477-9560-3-14
   PubMedGoogle Scholar
• Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005;106(8):2710–2715. doi:10.1182/blood-2005-04-1546
   PubMed Web of Science ®Google Scholar
• Warkentin TE, Sheppard JAI, Horsewood P, Simpson PJ, Moore JC, Kelton JG. Impact of the patient population on the risk for heparin-induced thrombocytopenia. Blood. 2000;96(5):1703–1708.
   PubMed Web of Science ®Google Scholar
• Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996;101(5):502–507. doi:10.1016/s0002-9343(96)00258-6
   PubMed Web of Science ®Google Scholar
• Pouplard C, Amiral J, Borg JY, Laporte-Simitsidis S, Delahousse B, Gruel Y. Decision analysis for use of platelet aggregation test, carbon 14- serotonin release assay, and heparin-platelet factor 4 enzyme-linked immunosorbent assay for diagnosis of heparin-induced thrombocytopenia. Am J Clin Pathol. 1999;111(5):700–706. doi:10.1093/ajcp/111.5.700
   PubMed Web of Science ®Google Scholar
• Vakil NH, Kanaan AO, Donovan JL. Heparin-induced thrombocytopenia in the pediatric population: a review of current literature. J Pediatr Pharmacol Ther. 2012;17(1):12–30. doi:10.5863/1551-6776-17.1.12
   PubMedGoogle Scholar
• Avila ML, Shah V, Brandão LR. Systematic review on heparin-induced thrombocytopenia in children: a call to action. J Thromb Haemost. 2013;11(4):660–669. PMID: 23350790. doi:10.1111/jth.12153
   PubMed Web of Science ®Google Scholar
• Takemoto CM, Streiff MB. Heparin-induced thrombocytopenia screening and management in pediatric patients. Hematology Am Soc Hematol Educ Program. 2011;2011(1):162–169. doi:10.1182/asheducation-2011.1.162
   PubMedGoogle Scholar
• Strauss R, Wehler M, Mehler K, Kreutzer D, Koebnick C, Hahn EG. Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence, transfusion requirements, and outcome. Crit Care Med. 2002;30(8):1765–1771. doi:10.1097/00003246-200208000-00015
   PubMed Web of Science ®Google Scholar
• 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. doi:10.1378/chest.126.3_suppl.311S
   PubMedGoogle Scholar
• Klenner AF, Lubenow N, Raschke R, Greinacher A. Heparin-induced thrombocytopenia in children: 12 new cases and review of the literature. Thromb Haemost. 2004;91(4):719–724. PMID: 15045133. doi:10.1160/TH03-09-0571
   PubMedGoogle Scholar
• Risch L, Huber AR, Schmugge M. Diagnosis and treatment of heparin-induced thrombocytopenia in neonates and children. Thromb Res. 2006;118(1):123–135. doi:10.1016/j.thromres.2004.12.020
   PubMedGoogle Scholar
• Vergara ACZ, Sotelo MAP, Pérez IST. Heparin - induced thrombocytopenia in pediatrics mini review. J Pediatr Care. 2019;5(3):2. doi:10.36648/2471-805X.5.3.100038
   Google Scholar
• Kadidal VV, Mayo DJ, Horne MK. Heparin-induced thrombocytopenia (HIT) due to heparin flushes: a report of three cases. J Intern Med. 1999;246(3):325–329. PMID: 10476001. doi:10.1046/j.1365-2796.1999.00527.x
   PubMedGoogle Scholar
• Reilly RF. The pathophysiology of immune-mediated heparin-induced thrombocytopenia. Semin Dial. 2003;16(1):54–60. doi:10.1046/j.1525-139x.2003.03013.x
   PubMed Web of Science ®Google Scholar
• Sato Y, Abe M, Takaki R. Platelet factor 4 blocks the binding of basic fibroblast growth factor to the receptor and inhibits the spontaneous migration of vascular endothelial cells. Biochem Biophys Res Commun. 1990;172(2):595–600. PMID: 2173572. doi:10.1016/0006-291x(90)90715-y
   PubMed Web of Science ®Google Scholar
• Arepally GM, Mayer IM. Antibodies from patients with heparin-induced thrombocytopenia stimulate monocytic cells to express tissue factor and secrete interleukin-8. Blood. 2001;98(4):1252–1254. doi:10.1182/blood.v98.4.1252
   PubMed Web of Science ®Google Scholar
• Aster RH. Heparin-induced thrombocytopenia and thrombosis. N Engl J Med. 1995;332(20):1374–1376. PMID: 7715648. doi:10.1056/NEJM199505183322011
   PubMedGoogle Scholar
• Cines DB, Tomaski A, Tannenbaum S. Immune endothelial-cell injury in heparin-associated thrombocytopenia. N Engl J Med. 1987;316(10):581–589. doi:10.1056/NEJM198703053161004
   PubMed Web of Science ®Google Scholar
• Dager WE, Dougherty JA, Nguyen PH, Militello MA, Smythe MA. Heparin-induced thrombocytopenia: treatment options and special considerations. Pharmacotherapy. 2007;27(4):564–587. doi:10.1592/phco.27.4.564
   PubMedGoogle Scholar
• Pouplard C, Iochmann S, Renard B, et al. Induction of monocyte tissue factor expression by antibodies to heparin-platelet factor 4 complexes developed in heparin-induced thrombocytopenia. Blood. 2001;97(10):3300–3302. doi:10.1182/blood.v97.10.3300
   PubMedGoogle Scholar
• Fenton JW, Ofosu FA, Brezniak DV, Hassouna HI. Thrombin and antithrombotics. Semin Thromb Hemost. 1998;24(2):87–91. PMID: 9579630. doi:10.1055/s-2007-995828
   PubMed Web of Science ®Google Scholar
• Verstraete M. Direct thrombin inhibitors: appraisal of the antithrombotic/hemorrhagic balance. Thromb Haemost. 1997;78(1):357–363.
   PubMedGoogle Scholar
• Gruel Y, Pouplard C, Nguyen P, et al.; French Heparin-Induced Thrombocytopenia Study Group. Biological and clinical features of low-molecular-weight heparin-induced thrombocytopenia. Br J Haematol. 2003;121(5):786–792. doi:10.1046/j.1365-2141.2003.04363.x
   PubMed Web of Science ®Google Scholar
• Ahmad S, Haas S, Hoppensteadt DA, et al. Differential effects of clivarin and heparin in patients undergoing Hip and knee surgery for the generation of anti-heparin-platelet factor 4 antibodies. Thromb Res. 2002;108(1):49–55. doi:10.1016/s0049-3848(02)00397-3
   PubMed Web of Science ®Google Scholar
• Warkentin TE. Heparin-induced thrombocytopenia: a clinicopathologic syndrome. Thromb Haemost. 1999;82(2):439–447. PMID: 10605735.
   PubMedGoogle Scholar
• Lubenow N, Kempf R, Eichner A, Eichler P, Carlsson LE, Greinacher A. Heparin-induced thrombocytopenia: temporal pattern of thrombocytopenia in relation to initial use or reexposure to heparin. Chest. 2002;122(1):37–42. doi:10.1378/chest.122.1.37
   PubMedGoogle Scholar
• Kelton JG. Heparin-induced thrombocytopenia: an overview. Blood Rev. 2002;16(1):77–80. doi:10.1054/blre.2001.0189
   PubMed Web of Science ®Google Scholar
• Warkentin TE, Linkins LA. Non-necrotizing heparin-induced skin lesions and the 4T’s score. J Thromb Haemost. 2010;8(7):1483–1485. doi:10.1111/j.1538-7836.2010.03880.x
   PubMed Web of Science ®Google Scholar
• Crowther MA, Cook DJ, Albert M, et al.; Canadian Critical Care Trials Group. The 4Ts scoring system for heparin-induced thrombocytopenia in medical-surgical intensive care unit patients. J Crit Care. 2010;25(2):287–293. doi:10.1016/j.jcrc.2009.12.006
   PubMed Web of Science ®Google Scholar
• Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006;4(4):759–765. doi:10.1111/j.1538-7836.2006.01787.x
   PubMed Web of Science ®Google Scholar
• Obeng EA, Harney KM, Moniz T, Arnold A, Neufeld EJ, Trenor CC. Pediatric heparin-induced thrombocytopenia: prevalence, thrombotic risk, and application of the 4Ts scoring system. J Pediatr. 2015;166(1):144–150. doi:10.1016/j.jpeds.2014.09.017
   PubMed Web of Science ®Google Scholar
• Cuker A, Arepally G, Crowther MA, et al. The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion. J Thromb Haemost. 2010;8(12):2642–2650. doi:10.1111/j.1538-7836.2010.04059.x
   PubMed Web of Science ®Google Scholar
• Cohen O, Lange K, Budnik I, et al. Application of a clinical decision rule and laboratory assays in pediatrics: adult heparin-induced thrombocytopenia. Pediatr Blood Cancer. 2022;69(11):e29929. doi:10.1002/pbc.29929
   PubMedGoogle Scholar
• Pouplard C, Leroux D, Regina S, Rollin J, Gruel Y. Effectiveness of a new immunoassay for the diagnosis of heparin-induced thrombocytopenia and improved specificity when detecting IgG antibodies. Thromb Haemost. 2010;103(1):145–150. doi:10.1160/TH09-04-0253
   PubMedGoogle Scholar
• Warkentin TE, Sheppard JA, Moore JC, Moore KM, Sigouin CS, Kelton JG. Laboratory testing for the antibodies that cause heparin-induced thrombocytopenia: how much class do we need? J Lab Clin Med. 2005;146(6):341–346. doi:10.1016/j.lab.2005.08.003
   PubMed Web of Science ®Google Scholar
• Fabris F, Luzzatto G, Soini B, et al. Risk factors for thrombosis in patients with immune mediated heparin-induced thrombocytopenia. J Intern Med. 2002;252(2):149–154. doi:10.1046/j.1365-2796.2002.01021.x
   PubMedGoogle Scholar
• Zwicker JI, Uhl L, Huang WY, Shaz BH, Bauer KA. Thrombosis and ELISA optical density values in hospitalized patients with heparin-induced thrombocytopenia. J Thromb Haemost. 2004;2(12):2133–2137. doi:10.1111/j.1538-7836.2004.01039.x
   PubMed Web of Science ®Google Scholar
• Schmugge M, Risch L, Huber AR, Benn A, Fischer JE. Heparin-induced thrombocytopenia-associated thrombosis in pediatric intensive care patients. Pediatrics. 2002;109(1):E10. doi:10.1542/peds.109.1.e10
   PubMed Web of Science ®Google Scholar
• Yuan SM. Heparin-induced Thrombocytopenia in Pediatrics Following Cardiopulmonary Bypass. J Coll Physicians Surg Pak. 2019;29(10):986–992. doi:10.29271/jcpsp.2019.10.986
   PubMed Web of Science ®Google Scholar
• Cosmi B. Current management of heparin-induced thrombocytopenia. Expert Rev Hematol. 2015;8(6):837–849. doi:10.1586/17474086.2015.1087845
   PubMed Web of Science ®Google Scholar
• Kelton JG, Arnold DM, Bates SM. Nonheparin anticoagulants for heparin-induced thrombocytopenia. N Engl J Med. 2013;368(8):737–744. doi:10.1056/NEJMct1206642
   PubMed Web of Science ®Google Scholar
• Vanholder R, Dhondt A. Recombinant Hirudin. BioDrugs. 1999;11:417–429. doi:10.2165/00063030-199911060-00006
   PubMedGoogle Scholar
• Keng TB, Chong BH. Heparin-induced thrombocytopenia and thrombosis syndrome: in vivo cross-reactivity with danaparoid and successful treatment with r-Hirudin. Br J Haematol. 2001;114(2):394–396. doi:10.1046/j.1365-2141.2001.02943.x
   PubMed Web of Science ®Google Scholar
• Murray PT, Reddy BV, Grossman EJ, et al. A prospective comparison of three argatroban treatment regimens during hemodialysis in end-stage renal disease. Kidney Int. 2004;66(6):2446–2453. doi:10.1111/j.1523-1755.2004.66022.x
   PubMed Web of Science ®Google Scholar
• Gosselin RC, Dager WE, King JH, et al. Effect of direct thrombin inhibitors, bivalirudin, lepirudin, and argatroban, on prothrombin time and INR values. Am J Clin Pathol. 2004;121(4):593–599. doi:10.1309/D79K-4YG7-8NTN-YY38
   PubMed Web of Science ®Google Scholar