{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:19:36Z","timestamp":1787242776337,"version":"build-2736575974"},"reference-count":40,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Heparin-induced thrombocytopenia, or HIT, can present in many ways, ranging from common\u2014isolated thrombocytopenia, venous thromboembolism, acute limb ischemia\u2014to less common but specific presentations\u2014necrotizing skin lesions at heparin injection sites, post-bolus acute systemic reactions, and adrenal hemorrhagic necrosis (secondary to adrenal vein thrombosis). Many patients with HIT have mild or moderate thrombocytopenia: the median platelet count nadir is 60 \u00d7 109\/L, and ranges from 15 to 150 \u00d7 109\/L in 90% of patients, most of whom evince a 50% or greater fall in the platelet count. HIT that begins after stopping heparin (\u201cdelayed-onset HIT\u201d) is increasingly recognized. Factors influencing risk of HIT include type of heparin (unfractionated heparin &gt; low-molecular-weight heparin), type of patient (surgical &gt; medical), and gender (female &gt; male). Since timely diagnosis and treatment of HIT may reduce the risk of adverse outcomes, this review focuses on those clinical circumstances that should prompt the clinician to \u201cthink of HIT.\u201d Coumarin anticoagulants such as warfarin are ineffective in acute HIT and can even be deleterious by predisposing to micro-thrombosis via protein C depletion (venous limb gangrene and skin necrosis syndromes). Thus, it is important to avoid or postpone coumarin while managing HIT hypercoagulability, focusing on agents that inhibit thrombin directly (lepirudin, argatroban) or that inhibit its generation (danaparoid, ?fondaparinux). Post-marketing experience suggests that standard dosing of lepirudin is too high; current recommendations are to avoid the initial lepirudin bolus and to begin with lower infusion rates, even in patients without overt renal dysfunction.<\/jats:p>","DOI":"10.1182\/asheducation-2006.1.408","type":"journal-article","created":{"date-parts":[[2006,11,22]],"date-time":"2006-11-22T18:14:02Z","timestamp":1164219242000},"page":"408-414","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":71,"title":["Think of HIT"],"prefix":"10.1182","volume":"2006","author":[{"given":"Theodore E.","family":"Warkentin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2019111704254129700_R1","unstructured":"Warkentin TE. Coumarin-induced skin necrosis and venous limb gangrene. In: Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2006:1663\u20131671."},{"key":"2019111704254129700_R2","doi-asserted-by":"crossref","unstructured":"Warkentin TE. Management of heparin-induced thrombocytopenia: a critical comparison of lepirudin and argatroban. Thromb Res. 2003;110:73\u201382.","DOI":"10.1016\/S0049-3848(03)00336-0"},{"key":"2019111704254129700_R3","doi-asserted-by":"crossref","unstructured":"Warkentin TE, Elevathil LJ, Hayward CPM, Johnston MA, Russett JI, Kelton JG. The pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia. Ann Intern Med. 1997;127:804\u2013812.","DOI":"10.7326\/0003-4819-127-9-199711010-00005"},{"key":"2019111704254129700_R4","doi-asserted-by":"crossref","unstructured":"Warkentin TE. An overview of the heparin-induced thrombocytopenia syndrome. Semin Thromb Hemost. 2004;30:273\u2013283.","DOI":"10.1055\/s-2004-831039"},{"key":"2019111704254129700_R5","doi-asserted-by":"crossref","unstructured":"Lee DH, Warkentin TE. Frequency of heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A, eds. Heparin-Induced Thrombocytopenia, 3rd ed. New York: Marcel Dekker; 2004;107\u2013148.","DOI":"10.1201\/9780824758844"},{"key":"2019111704254129700_R6","doi-asserted-by":"crossref","unstructured":"Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005;106:2710\u20132715.","DOI":"10.1182\/blood-2005-04-1546"},{"key":"2019111704254129700_R7","doi-asserted-by":"crossref","unstructured":"Warkentin TE, Sheppard JI, Sigouin CS, Kohlmann T, Eichler P, Greinacher A. Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood. 2006 Jul 20; [Epub ahead of print].","DOI":"10.1182\/blood-2005-11-012450"},{"key":"2019111704254129700_R8","doi-asserted-by":"crossref","unstructured":"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\u2013337S.","DOI":"10.1378\/chest.126.3_suppl.311S"},{"key":"2019111704254129700_R9","doi-asserted-by":"crossref","unstructured":"Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T\u2019s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006;4:759\u2013765.","DOI":"10.1111\/j.1538-7836.2006.01787.x"},{"key":"2019111704254129700_R10","doi-asserted-by":"crossref","unstructured":"Warkentin TE, Roberts RS, Hirsh J, Kelton JG. An improved definition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients. Arch Intern Med. 2003;163:2518\u20132524.","DOI":"10.1001\/archinte.163.20.2518"},{"key":"2019111704254129700_R11","doi-asserted-by":"crossref","unstructured":"Pouplard C, May MA, Regina S, Marchand M, Fusciardi J, Gruel Y. Changes in platelet count after cardiac surgery can effectively predict the development of pathogenic heparin-dependent antibodies. Br J Haematol. 2005;128:837\u2013841.","DOI":"10.1111\/j.1365-2141.2005.05381.x"},{"key":"2019111704254129700_R12","doi-asserted-by":"crossref","unstructured":"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 analysis of 408 patients. Thromb Haemost. 2005;94:132\u2013135.","DOI":"10.1160\/TH04-12-0825"},{"key":"2019111704254129700_R13","unstructured":"Warkentin TE. Clinical presentation of heparin-induced thrombocytopenia. Semin Hematol. 1998;35(Suppl. 5):9\u201316."},{"key":"2019111704254129700_R14","doi-asserted-by":"crossref","unstructured":"Brinker AD, Beitz J. Spontaneous reports of thrombocytopenia in association with quinine: clinical attributes and timing related to regulatory action. Am J Hematol. 2002;70:313\u2013317.","DOI":"10.1002\/ajh.10148"},{"key":"2019111704254129700_R15","doi-asserted-by":"crossref","unstructured":"Warkentin TE. Clinical picture of heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A, eds. Heparin-Induced Thrombocytopenia, 3rd ed. New York: Marcel Dekker; 2004:53\u2013106.","DOI":"10.1201\/9780824758844"},{"key":"2019111704254129700_R16","doi-asserted-by":"crossref","unstructured":"Warkentin TE, Roberts RS, Hirsh J, Kelton JG. Heparin-induced skin lesions and other unusual sequelae of the heparin-induced thrombocytopenia syndrome: a nested cohort study. Chest. 2005;127:1857\u20131861.","DOI":"10.1378\/chest.127.5.1857"},{"key":"2019111704254129700_R17","doi-asserted-by":"crossref","unstructured":"Mims MP, Manian P, Rice L. Acute cardiorespiratory collapse from heparin: a consequence of heparin-induced thrombocytopenia. Eur J Haematol. 2004;72:366\u2013369.","DOI":"10.1111\/j.1600-0609.2004.00224.x"},{"key":"2019111704254129700_R18","unstructured":"Warkentin TE. Heparin-induced thrombocytopenia. Curr Hematol Rep. 2002;1:63\u201372."},{"key":"2019111704254129700_R19","doi-asserted-by":"crossref","unstructured":"Warkentin TE, Bernstein RA. Delayed-onset heparin-induced thrombocytopenia and cerebral thrombosis after a single administration of unfractionated heparin. N Engl J Med. 2003;348:1067\u20131069.","DOI":"10.1056\/NEJM200303133481120"},{"key":"2019111704254129700_R20","doi-asserted-by":"crossref","unstructured":"Warkentin TE, Kelton JG. Delayed-onset heparin-induced thrombocytopenia and thrombosis. Ann Intern Med. 2001;135:502\u2013506.","DOI":"10.7326\/0003-4819-135-7-200110020-00009"},{"key":"2019111704254129700_R21","doi-asserted-by":"crossref","unstructured":"Rice L, Attisha WK, Drexler A, Francis JL. Delayed-onset heparin-induced thrombocytopenia. Ann Intern Med. 2002;136:210\u2013215.","DOI":"10.7326\/0003-4819-136-3-200202050-00009"},{"key":"2019111704254129700_R22","doi-asserted-by":"crossref","unstructured":"Rauova L, Zhai L, Kowalska MA, Arepally GM, Cines DB, Poncz M. Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications. Blood. 2006;107:2346\u20132353.","DOI":"10.1182\/blood-2005-08-3122"},{"key":"2019111704254129700_R23","doi-asserted-by":"crossref","unstructured":"Warkentin TE, Jay RM, Makris M, Kelton JG. Platelet-activating anti-platelet factor 4\/polyanion antibodies without preceding heparin therapy: a transient autoimmune disorder resembling heparin-induced thrombocytopenia (\u201cspontaneous HIT\u201d) [abstract]. Blood. 2006; in press.","DOI":"10.1182\/blood.V108.11.1047.1047"},{"key":"2019111704254129700_R24","doi-asserted-by":"crossref","unstructured":"Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996;101:502\u2013507.","DOI":"10.1016\/S0002-9343(96)00258-6"},{"key":"2019111704254129700_R25","doi-asserted-by":"crossref","unstructured":"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;2:2133\u20132137.","DOI":"10.1111\/j.1538-7836.2004.01039.x"},{"key":"2019111704254129700_R26","doi-asserted-by":"crossref","unstructured":"Napolitano L, Warkentin TE, AlMahameed A, Nasraway SA. Heparin-induced thrombocytopenia in the critical care setting. Crit Care Med. 2006; in press.","DOI":"10.1097\/01.CCM.0000248723.18068.90"},{"key":"2019111704254129700_R27","doi-asserted-by":"crossref","unstructured":"Levine RL, McCollum D, Hursting MJ. How frequently is venous thromboembolism in heparin-treated patients associated with heparin-induced thrombocytopenia? Chest. 2006;130:681\u2013687.","DOI":"10.1378\/chest.130.3.681"},{"key":"2019111704254129700_R28","doi-asserted-by":"crossref","unstructured":"Francis JL, Drexler A, Walker J, Duncan MK, Ahmad S. Heparin-platelet factor 4 antibodies are common among recently hospitalized patients with acute coronary syndromes presenting to the emergency department [abstract]. J Thromb Haemost.2005;P1514.","DOI":"10.1182\/blood.V104.11.2067.2067"},{"key":"2019111704254129700_R29","doi-asserted-by":"crossref","unstructured":"Yusuf S, Mehta SR, Chrolavicius S, et al; Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006;354:1464\u20131476.","DOI":"10.1056\/NEJMoa055443"},{"key":"2019111704254129700_R30","doi-asserted-by":"crossref","unstructured":"Warkentin TE, Cook RJ, Marder VJ, et al. Anti-platelet factor 4\/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin. Blood. 2005;106:3791\u20133796.","DOI":"10.1182\/blood-2005-05-1938"},{"key":"2019111704254129700_R31","doi-asserted-by":"crossref","unstructured":"Warkentin TE. Should vitamin K be administered when HIT is diagnosed after administration of coumarin? J Thromb Haemost. 2006;4:894\u2013896.","DOI":"10.1111\/j.1538-7836.2006.01875.x"},{"key":"2019111704254129700_R32","doi-asserted-by":"crossref","unstructured":"Lubenow N, Eichler P, Lietz T, Greinacher A, HIT Investigators Group. Lepirudin in patients with heparin-induced thrombocytopenia\u2014results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3. J Thromb Haemost. 2005;3:2428\u20132436.","DOI":"10.1111\/j.1538-7836.2005.01623.x"},{"key":"2019111704254129700_R33","doi-asserted-by":"crossref","unstructured":"Hacquard M, de Maistre E, Lecompte T. Lepirudin: is the approved dosing schedule too high? J Thromb Haemost. 2005;3:2593\u20132596.","DOI":"10.1111\/j.1538-7836.2005.01620.x"},{"key":"2019111704254129700_R34","doi-asserted-by":"crossref","unstructured":"Tardy B, Lecompte T, Boelhen F, et al. Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin. Blood.2006;108:1492\u20131496 [Epub 2006 May 11]","DOI":"10.1182\/blood-2006-02-001057"},{"key":"2019111704254129700_R35","doi-asserted-by":"crossref","unstructured":"Kodityal S, Nguyen PH, Kodityal A, Sherer J, Hursting MJ, Rice L. Argatroban for suspected heparin-induced thrombocytopenia: contemporary experience at a large teaching hospital. J Intensive Care Med. 2006;21:86\u201392.","DOI":"10.1177\/0885066605284590"},{"key":"2019111704254129700_R36","doi-asserted-by":"crossref","unstructured":"Warkentin TE, Greinacher A, Craven S, Dewar L, Sheppard JI, Ofosu FA. Differences in the clinically effective molar concentrations of four direct thrombin inhibitors explain their variable prothrombin time prolongation. Thromb Haemost. 2005;94:958\u2013964.","DOI":"10.1160\/TH05-03-0154"},{"key":"2019111704254129700_R37","doi-asserted-by":"crossref","unstructured":"Lewis BE, Wallis DE, Hursting MJ, Levine RL, Leya F. Effects of argatroban therapy, demographic variables, and platelet count on thrombotic risks in heparin-induced thrombocytopenia. Chest. 2006;129:1407\u20131416.","DOI":"10.1378\/chest.129.6.1407"},{"key":"2019111704254129700_R38","doi-asserted-by":"crossref","unstructured":"Lubenow N, Warkentin TE, Greinacher A, et al. Results of a systematic evaluation of treatment outcomes for heparin-induced thrombocytopenia in patients receiving danaparoid, ancrod, and\/or coumarin explain the rapid shift in clinical practice during the 1990s. Thromb Res. 2006;117:507\u2013515.","DOI":"10.1016\/j.thromres.2005.04.011"},{"key":"2019111704254129700_R39","doi-asserted-by":"crossref","unstructured":"Warkentin TE, Sheppard JI, 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;146:341\u2013346.","DOI":"10.1016\/j.lab.2005.08.003"},{"key":"2019111704254129700_R40","doi-asserted-by":"crossref","unstructured":"Juhl D, Eichler P, Lubenow N, Strobel U, Wessel A, Greinacher A. Incidence and clinical significance of anti-PF4\/heparin antibodies of the IgG, IgM, and IgA class in 755 consecutive patients samples referred for diagnostic testing for heparin-induced thrombocytopenia. Eur J Haematol. 2006;76:420\u2013426.","DOI":"10.1111\/j.1600-0609.2005.00621.x"}],"container-title":["Hematology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2006\/1\/408\/1091551\/408_414ash.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2006\/1\/408\/1091551\/408_414ash.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T21:24:59Z","timestamp":1628112299000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/hematology\/article\/2006\/1\/408\/19776\/Think-of-HIT"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1,1]]}},"URL":"https:\/\/doi.org\/10.1182\/asheducation-2006.1.408","relation":{},"ISSN":["1520-4391","1520-4383"],"issn-type":[{"value":"1520-4391","type":"print"},{"value":"1520-4383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1,1]]}}}