Autoimmune heparin-induced thrombocytopenia.
J Thromb Haemost. 2017 Aug 28;:
Authors: Greinacher A, Selleng K, Warkentin TE
Abstract
Autoimmune heparin-induced thrombocytopenia (aHIT) indicates patients with anti-PF4/polyanion antibodies that are able to activate platelets strongly even in the absence of heparin (heparin-independent platelet activation). Nevertheless, as seen with serum obtained from patients with otherwise typical HIT, serum-induced platelet activation is inhibited at high heparin concentrations (10-100 IU/mL heparin). Further, upon serial dilution, aHIT serum will usually exhibit heparin-dependent platelet activation. Clinical syndromes associated with aHIT include: delayed-onset HIT, persisting HIT, spontaneous HIT, fondaparinux-associated HIT, heparin "flush"-induced HIT, and severe HIT (platelet count <20×10(9) /L) with associated disseminated intravascular coagulation (DIC). Recent studies implicate anti-PF4 antibodies that are able to bridge two PF4 tetramers even in the absence of heparin, likely facilitated by non-heparin platelet-associated polyanions (chondroitin sulfate, polyphosphates); nascent PF4-aHIT-IgG complexes recruit additional heparin-dependent HIT antibodies, leading to formation of large multimolecular immune complexes and marked platelet activation. aHIT can persist for several weeks, and serial fibrin d-dimers and fibrinogen levels, rather than the platelet count, may be helpful to monitor treatment response. Although standard anticoagulant therapy for HIT ought to be effective, published experience indicates frequent failure of partial thromplastin time (PTT)-adjusted anticoagulants (argatroban, bivalirudin), probably due to underdosing in the setting of HIT-associated DIC, known as "PTT confounding." Thus, non-PTT-adjusted therapies such as danaparoid and fondaparinux or even direct oral anticoagulants, such as rivaroxaban or apixaban, are suggested therapies, especially for long-term management of persisting HIT. In addition, emerging data indicate that high-dose intravenous gammaglobulin can interrupt HIT antibody-induced platelet activation, leading to rapid platelet count recovery. This article is protected by copyright. All rights reserved.
PMID: 28846826 [PubMed - as supplied by publisher]