Efficacy and Safety of Off‐Label Use of Fondaparinux in the Management of Heparin‐Induced Thrombocytopenia with Thrombosis in an Elderly Woman

Abstract

Type II heparin‐induced thrombocytopenia (HIT) represents the most common immune‐mediated adverse drug reaction (ADR), during treatment with unfractionated heparin (UFH) or low molecular weight heparins (LMWHs). The frequency of HIT is about 2–3% in surgical divisions (e.g., Cardiac Surgery and Orthopedics) and about 0.5–1% in medical divisions (e.g., Internal Medicine). HIT can develop in 5–10 days after the beginning of heparin and it is induced by the production of antibodies targeting a molecular complex of both “self” protein, that is platelet factor 4 (PF4), and heparin. This induces platelet activation as well as increased thrombin production, that result in a higher risk of venous or arterial thrombosis. When thrombosis is identified, HIT is called HIT‐ associated thrombosis (HITT). Identification of a decrease in platelet count represents the first step in the diagnosis of HIT. However, other clinical and laboratory tests, such as 4Ts score serotonin‐release assay (SRA) and measurement of heparin/PF4 antibodies, must be also used. 4Ts score is a clinical scoring system used to estimate the pretest probability of HIT1, based on its characteristic features (Thrombocytopenia, Timing, Thrombosis) and absence of oTher explanation(s). 4Ts score (Table 1) is also used in the pharmacological management of HIT: score 3 continue heparin, score >4 change heparin to non‐heparin anticoagulants. Among non‐heparin anticoagulants, only lepirudin and argatroban, direct thrombin inhibitors (DTIs), are approved in the treatment of HIT. Another DTI, bivalirudin, is indicated in patients undergoing percutaneous coronary interventions. Danaparoid, a factor Xa inhibitor, is not currently available in Italy, but it is approved for treatment and prevention of HITT in Canada, continental Europe, Australia, New Zealand, and Japan. Finally, fondaparinux sodium, a synthetic antithrombin‐binding pentasaccharide with exclusive anti‐factor Xa activity, has shown favorable results in HIT, although in Italy it is off‐label for this indication. In this paper, we report a case of HITT during treatment with a LMWH, that was successfully treated with an off‐ label administration of fondaparinux sodium.