H eparin-induced thrombocytopenia (HIT) is a prothrombotic adverse reaction to heparin characterised by platelet-activating antibodies (almost exclusively IgG) that recognise and bind to platelet factor 4 (PF4)-heparin complexes. While antibody formation is common (up to 50% in the setting of cardiac surgery), only a small proportion of patients (0.2-3.0%) develop HIT (ie, thrombocytopenia and/or thrombosis). 1 Thrombosis can be arterial, venous or microvascular. Incidence of HIT varies depending on clinical setting (higher in surgical than medical, rarely in paediatric or obstetric), type of heparin (unfractionated heparin has higher rates than low molecular weight heparin), and dose (therapeutic v prophylactic). 2 PF4 tetramers (cationic) and heparin (anionic) associate by charge and hence certain molar concentrations (1:1 molar ratio) facilitate charge neutralisation, conformational change in PF4-exposing pathogenic epitopes, antibody binding and PF4-heparin-IgG complex formation. 3 PF4 can also bind to other polyanions, including glycosaminoglycans and chondroitin sulfate, and such interactions may play a role in the increasingly reported entity known as spontaneous HIT syndrome; that is, patients with clinical and laboratory features of HIT without exposure to heparin.Thrombocytopenia and thrombosis in HIT result from the binding of PF4-heparin-IgG complex to FcγRIIa receptors on the platelet surface. Subsequent cross-linking of the receptors leads to intense platelet activation, release of platelet granule content and procoagulant microparticles, thrombin generation, and activation of endothelial cells, neutrophils and monocytes. 4HIT is a clinicopathological entity and therefore requires integration of clinical and laboratory results. Accurate diagnosis is important and consultation with an appropriate specialist is recommended as delay in diagnosis and appropriate anticoagulant treatment is associated with an initial 6% daily risk of thromboembolism as well as amputation and death. 5
MethodsAustralian and New Zealand experts in the field of thrombosis and haemostasis who regularly diagnose and treat HIT syndrome were invited to a consensus statement development panel. This group, the Thrombosis and Haemostasis Society of Australia and New Zealand (THANZ) HIT Writing Group, represents THANZ members and received formal endorsement from the THANZ President. A comprehensive literature review, using common online databases, was undertaken for each subsection by at least two authors. Major computerised databases such as Cochrane, MEDLINE and EMBASE were utilised. These searches were further supplemented with review of reference lists and professional society information available from internet sources. A draft for each subsection, collated by its two authors after extensive literature review, was submitted to the lead author (JJ). Following this comprehensive review of the literature, a face-to-face meeting was held over 2 days to discuss specific questions and finalise a draft of the consensus statement. Durin...