In vivo and in vitro cross-reactivity to fondaparinux in a stroke patient with IgG-PF4/heparin antibody-negative delayed-onset heparin-induced thrombocytopenia

Abstract

Introduction
Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction caused by IgG antibodies to complexes of platelet factor 4 (PF4) and heparin which can activate platelets, causing the release of prothrombotic platelet-derived microparticles that promote both arterial and venous thrombosis¹. Delayed-onset HIT is characterised by thrombocytopenia that begins or worsens several days after stopping heparin². These patients can be challenging to manage because of the very high titres of IgG antibodies to PF4/heparin complexes and higher IgG-induced heparin-dependent and heparin-independent platelet activation that causes life-threatening thrombosis and profound thrombocytopenia¹. First-line treatment of "classical" HIT includes stopping heparin and "switching" to a non-heparin anticoagulant, such as argatroban or bivalirudin^1,2. However, even in the absence of randomised trials, fondaparinux has been used worldwide to treat HIT, as the risk of HIT is thought to be negligible with this medication³. In this paper, we present a case of in vivo and in vitro cross-reactivity to fondaparinux in an ischaemic stroke patient with IgG-PF4/heparin antibody-negative delayed-onset HIT.