Case of Heparin Allergy and Preventive Administration of Fondaparinux in Pregnancy – Case Study

Case Description

ET was diagnosed in the patient at the age of 20. At that time, she started antiplatelet therapy with ticlopidine. Nine years later, she became pregnant for the first time and took acetylsalicylic acid (ASA) during the pregnancy. However, fetal death was diagnosed at 28 weeks of pregnancy. A year later, she experienced her first episode of PE without any proven cause, which led to the initiation of interferon in combination with ASA.

At the age of 30, she became pregnant again and was treated with low-molecular-weight heparin (nadroparin) and ASA, but had an early miscarriage, and three months later had another episode of PE. Shortly thereafter, she resumed nadroparin, but developed local urticaria, generalized itching, cough, and dysphagia within minutes after injection administration. A month later, she received the same LMWH again, exhibiting the same symptoms after the first dose. The symptoms were relieved with antihistamines and betamethasone.

She then underwent an allergy examination. Skin prick and intradermal tests for heparin, nadroparin, bemiparin, reviparin, dalteparin, and fondaparinux were performed. An IgE-mediated allergy to unfractionated heparin and all LMWHs except fondaparinux was identified. No adverse reaction was observed during the subcutaneous trial of fondaparinux at a dose of 2.5 mg.

At the age of 34, she became pregnant again. Warfarin prophylaxis was immediately discontinued, and fondaparinux was initiated at 2.5 mg once daily in combination with ASA at 100 mg daily. In the second trimester, ASA was stopped due to the detection of multiple amniochorionic detachments, with more favorable ultrasound results at 32 weeks of gestation. No allergic reaction or significant bleeding occurred during fondaparinux administration.

The pregnancy was terminated by planned cesarean section at 36 weeks, and fondaparinux was stopped 24 hours before the procedure. The patient delivered a healthy girl, with an uncomplicated postnatal course for the child. Fondaparinux was re-administered 12 hours after the procedure and continued once daily for 40 days postpartum.

Conclusion

Fondaparinux is a synthetic pentasaccharide with very low cross-reactivity with UFH or LMWH. It is generally well-tolerated in patients with hypersensitivity to heparin-based treatments. Although not recommended during pregnancy, fondaparinux provided effective prophylaxis in this pregnant woman with allergies to UFH and LMWH. However, risks associated with fondaparinux crossing the placenta should not be overlooked. The authors also recommend excluding cross-reactivity in patients with Type I or IV hypersensitivity before initiating fondaparinux.

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Source: Buonomo A., Nucera E., De Carolis S. et al. A case of heparin allergy with good tolerability to fondaparinux during pregnancy. J Investig Allergol Clin Immunol 2015; 25 (3): 229−231.