From the Guidelines
Fondaparinux can be used as an alternative anticoagulant for patients with heparin-induced thrombocytopenia (HIT), with a weight-based dosing regimen of 5 mg daily for patients weighing less than 50 kg, 7.5 mg daily for those 50-100 kg, and 10 mg daily for those over 100 kg, administered subcutaneously. Fondaparinux (Arixtra) is a synthetic pentasaccharide that selectively inhibits Factor Xa without binding to platelet factor 4 (PF4), which is the target of the antibodies that cause HIT 1. The use of fondaparinux in HIT is supported by several studies, including a retrospective study that compared 133 patients treated with fondaparinux with matched control patients using a propensity score, showing that the efficacy and safety of fondaparinux was comparable to that of argatroban or danaparoid administered to patients in the control group 1. Additionally, a German registry of 195 HIT patients showed that nearly half of them were treated with fondaparinux without complication or death, while 11.7% of cases treated with an approved anticoagulant had complications 1.
The advantages of using fondaparinux in HIT include its minimal cross-reactivity with heparin-PF4 antibodies, ease of administration, and lower cost compared to other anticoagulants such as danaparoid or argatroban 1. However, fondaparinux is not FDA-approved specifically for HIT, and its use in this setting is off-label. Renal function should be assessed before initiating therapy as fondaparinux is contraindicated in severe renal impairment (creatinine clearance <30 mL/min) 1. Unlike direct thrombin inhibitors, fondaparinux does not require routine monitoring of coagulation parameters.
Some studies have reported cases of possible fondaparinux-induced HIT, but the quality of the evidence for this is low, and experts dispute its existence 1. The use of fondaparinux in HIT is also supported by the American Society of Hematology guidelines, which provide weak conditional support for its use as an alternative anticoagulant in cases with confirmed or suspected HIT 1. Overall, fondaparinux can be a useful alternative anticoagulant for patients with HIT, particularly in stable patients with normal renal function.
From the FDA Drug Label
Occurrences of thrombocytopenia with thrombosis that manifested similar to heparin-induced thrombocytopenia have been reported with the use of fondaparinux sodium in postmarketing experience [see Adverse Reactions (6.5)]. The FDA drug label does not answer the question.
From the Research
Fondaparinux for Heparin-Induced Thrombocytopenia
- Fondaparinux has been used as an alternative anticoagulant in patients with heparin-induced thrombocytopenia (HIT) 2, 3, 4, 5, 6
- Studies have shown that fondaparinux is effective in preventing thromboembolic events and promoting platelet count recovery in patients with HIT 2, 3, 4, 6
- Fondaparinux has been used in patients with severe renal impairment, and its safety and efficacy in this population have been reported 2, 4
Efficacy and Safety of Fondaparinux
- A retrospective study found that fondaparinux was associated with a lower risk of thrombosis and bleeding compared to direct thrombin inhibitors (DTIs) 3
- Another study found that fondaparinux had similar effectiveness and safety as argatroban and danaparoid in patients with suspected HIT 6
- Fondaparinux has been shown to be safe and effective in postoperative cardiac surgery patients with HIT 4
Dosage and Administration
- Fondaparinux can be used at prophylactic or therapeutic doses in patients with HIT 5, 6
- The choice of dose should be individualized based on the patient's renal function and other clinical factors 2, 4
- Daily monitoring of platelet count and anti-Xa activity is recommended when using fondaparinux in patients with HIT 4