Fondaparinux Failure in Heparin-Induced Thrombocytopenia With Acute Limb Ischemia: A Case Report and Literature Review

Heparin-induced thrombocytopenia (HIT), a prothrombotic disorder caused by heparin-dependent antibodies, is often treated with fondaparinux, generally yielding positive outcomes. A 69-year-old male with a history of stage IIIb small cell lung cancer developed severe HIT (platelet count nadir, 11 × 10⁹/L) after receiving heparin for stroke prophylaxis, complicated by deep vein thrombosis (DVT) and acute limb ischemia (ALI). Despite treatment with fondaparinux, thrombocytopenia secondary to HIT persisted, and his arterial thrombosis progressed, leading to urgent angioplasty and thrombectomy. This clinical course raised concerns for autoimmune HIT (aHIT) refractory to fondaparinux or potential fondaparinux cross-reactivity. The patient was transitioned to argatroban postoperatively, resulting in rapid platelet recovery and clinical improvement. Our case highlights the limitations of fondaparinux in select HIT cases, particularly when aHIT is suspected, and underscores the need for vigilance in monitoring for treatment failure. This report adds to emerging data on alternative anticoagulation strategies for refractory HIT, including the potential role of direct thrombin inhibitors in severe cases.