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Blood, 14 May 2009, Vol. 113, No. 20, pp. 4970-4976. Prepublished online as a Blood First Edition Paper on December 23, 2008; DOI 10.1182/blood-2008-08-173062. This Article Full Text (PDF) All Versions of this Article: blood-2008-08-173062v1 113/20/4970    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Greinacher, A. Articles by Warkentin, T. E. Search for Related Content PubMed PubMed Citation Articles by Greinacher, A. Articles by Warkentin, T. E. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 8, 2008 Accepted December 4, 2008 The temporal profile of the anti-PF4/heparin immune response Andreas Greinacher*, Thomas Kohlmann, Ulrike Strobel, Jo-Ann I. Sheppard, and Theodore E. Warkentin Institut fur Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt Universitat, Greifswald, Germany Insitut fur Community Medicine, Ernst-Moritz-Arndt Universitat, Greifswald, Germany Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada * Corresponding author; email: greinach{at}uni-greifswald.de. The immune response in heparin-induced thrombocytopenia (HIT) is puzzling: heparin-naive patients can develop IgG antibodies and clinical HIT as early as day 5, and evidence for an even more rapid ("anamnestic") response upon heparin reexposure is lacking. We assessed daily serum samples by anti-PF4/heparin enzyme-immunoassay (EIA) in patients receiving heparin thromboprophylaxis, and followed patients during prolonged outpatient low-molecular-weight heparin (LMWH) thromboprophylaxis. Of 435 patients, 56.1% showed an increase in EIA optical density (OD) of 15%, with >90% starting between days 4-14. After reaching maximum reactivity by days 10-12, ODs declined despite heparin continuation, including in two patients with clinical HIT. Individual IgG/A/M classes showed identical time of onset (median, day 6). Most (58.7%) antibody-positive patients developed all three Ig classes; only 11.3% lacked IgG response. IgG/A/M increase usually occurred simultaneously (±1d) with no general tendency for IgM precedence. Consistent with the transient immune response, none of the IgG-EIA-positive (OD >0.5) patients at discharge developed clinically-evident thrombosis during extended LMWH-thromboprophylaxis. The rapid onset of the anti-PF4/heparin immune response, its transience, and the simultaneous appearance of antibodies of different classes with no IgM precedence suggest short-term activation of B-cells that have previously undergone Ig class switching even without previous pharmacologic heparin exposure. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Nothing typical about HIT Gowthami M. Arepally Blood 2009 113: 4825-4826. [Full Text] [PDF] This article has been cited by other articles: G. M. Arepally Nothing typical about HIT Blood, May 14, 2009; 113(20): 4825 - 4826. [Full Text] [PDF]

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