Cutaneous blood-filled vesicles on idraparinux.

In the Amadeus study, 1 patients in atrial fi brillation who had an increased risk of thromboembolic stroke were randomly assigned either a vitamin K antagonist or a weekly subcutaneous injection of idraparinux—a synthetic pentasaccharide that inhibits activated factor X. The study was stopped early because of excessive bleeding in patients assigned idraparinux. We report unusual skin lesions that occurred in 15 of 56 participants assigned open-label idraparinux compared with none of 59 patients assigned warfarin at our study site. After noting skin lesions in two study patients, we did detailed skin examinations on all study participants at each follow-up visit. We saw raised, blood-fi lled vesicles 0·5–2·0 cm in diameter that were remote from the subcutaneous injection sites in 15 patients (fi gure). Most patients had two to eight lesions, usually on the arms and legs, which appeared on average 3 months (range 2–8) after starting idraparinux. From this time new lesions continued to appear, but the severity of the lesions did not increase despite ongoing medication. On fi rst appearance the lesions would be bright red, suggesting fresh blood. They would then darken before gradually resolving over 2 weeks. The lesions were not painful or itchy, and occurred spontaneously with no trauma. The skin lesions continued after onset during a median follow-up of 5 months (range 1–10). In two patients the lesions disappeared over the course of 2 weeks after temporarily stopping idraparinux, but returned within 1 month on restarting idraparinux. In all patients, new lesions stopped appearing and gradually resolved 1 week after the last injection of idraparinux at study end with no subsequent recurrence. 2 These skin lesions did not meet the study defi nition of a clinically signifi cant bleed, which included a subcutaneous haematoma of more than 25 cm² or more than 100 cm² after trauma. Patients with vesicular skin lesions were no more likely to have a clinically signifi cant bleed than were idraparinux patients with no skin lesions (four of 15 vs 15 of 43), although both groups were more likely to bleed than were patients assigned warfarin (seven of 59). We found no evidence of other systemic abnormalities in patients with skin lesions, and the platelet count remained in the normal range for all patients. These skin lesions are likely to be a specifi c adverse eff ect of idraparinux. Raised, blood-fi lled vesicles with no history of trauma are not …