Successful treatment of heparin induced thrombocytopenia (HIT) with fondaparinux

Thromb Haemost 2005; 93: 999-1000 Heparin is a mainstay in the treatment and prevention of venous and arterial thromboembolism (1). However, its use is associated with a serious and potentially fatal immunological drug reaction termed heparin-induced thrombocytopenia (HIT) (2, 3). Current treatment of HIT includes the discontinuation of heparin and often the commencement of alternate anticoagulant therapy (1–4). Fondaparinux is a novel synthetic heparin pentasaccharide capable of inhibiting factor Xa via the action of antithrombin but is devoid of anti-IIa (thrombin) activity (5–7). Although the drug is identical in structure to the pentasaccharide domain found on unfractionated heparin (UH), it is too small to be recognized by the majority of heparin-reactive antibodies (8). We report the successful use of fondaparinux in the treatment of five patients with HIT. Five patients with heparin-induced thrombocytopenia and thrombosis were treated with fondaparinux at our institution. All five patients fulfill the diagnostic criteria of HIT as defined by Warkentin (4). The diagnosis of HIT in all patients was serologically confirmed by the platelet factor 4 complex enzyme linked immunosorbant assay (PF4 ELISA) method from GTI diagnostics (GTI, Waukesha, WI) run according to the manufacturer’s specifications. The time of onset of thrombocytopenia was defined as the interval between the initial dose of heparin and a > 50% decrease in platelet count or the onset of thrombosis.The initial platelet count was defined as the platelet count obtained immediately prior to the initial dose of heparin. In all cases, unfractionated heparin (UH) or low molecular weight heparin (LMWH) was discontinued and patients were treated with daily subcutaneous injections of 7.5 mg fondaparinux as soon as the diagnosis of HIT was made. Oral anticoagulation with warfarin was initiated when the platelet count was > 100x109/L. Fondaparinux was discontinued when the International Normalized Ratio (INR) was ≥ 2.0 for two consecutive days. The time to platelet count recovery was defined as number of days until the platelet count was at least 150x109/L while the patient was on fondaparinux. All patients were followed for 3 months for major bleeding, recurrent venous thromboembolism and survival. The Table summarizes the characteristics and clinical course of 5 patients with HIT treated with fondaparinux. The platelet count of all patients before heparin administration was normal. The average time of thrombocytopenia was 7 days (5 to 10 days) after the commencement of UH anticoagulation. The mean platelet count nadir was 43x109/L (5x109/L to 79x109/L). All 5 patients developed one or more thrombotic complications. Three patients were initially treated with dalteparin once the diagnosis of thrombosis was made but before the diagnosis of HIT was confirmed. None had renal impairment at the time of therapy.All patients responded with the platelet count normalizing between 2 and 9 days after initiation of fondaparinux treatment. There were no episodes of major bleeding or recurrent thrombosis during three months follow-up. One patient died from her underlying malignancy 5 weeks after the diagnosis of HIT was made. To our knowledge this is the first successful report of fondaparinux for the treatment of HIT complicated by active thrombo-