Peak and baseline concentrations of fondaparinux during prophylactic therapy. Results of a prospective investigation under "real life" clinical practice conditions

Fondaparinux is widely approved for prophylaxis and Treatment of venous thromboembolic events (VTE). However, its longer halflife time compared to heparins limits its periprocedural use. Aim: To investigate 3h peak and 24h baseline concentrations of fondaparinux when administered for prophylaxis (1 x 2.5 mg qd). Secondary outcome measures: incidences of VTE, bleedings, HIT, allergic skin reactions, 30 days mortality. Patients, methods: Between 02/2010 and 03/2011, 3h peak and 24h baseline levels of fondaparinux were measured with a chromogenic anti-FXa method in 75 consecutive patients. Medical data were obtained from patients' records. Results: The 5% and 95% percentile of the 3h peak level were 0.20 μg/ml and 0.83 μg/ml (median: 0.53 μg/ml), and of the 24h baseline level 0.08 μg/ml and 0.53 μg/ml (median 0.21 μg/ml), respectively. An inverse correlation was found between fondaparinux levels and GFRs (rho=-0.617 (3h); rho=-0.648 (24h); p=0.01). Shorter (≤5 days) or longer (≥8 days) duration of prior fondaparinux exposure showed no significantly different 3h peak/24h baseline levels (p>0.6). One progressive thrombosis occurred but no major bleedings, HIT, allergic skin reactions or fatalities. Conclusions: After fondaparinux exposure, >75% of the patients still had relevant prophylactic 24h baseline levels. This did not coincide with a high rate of bleeding events. Due to the low patient number in this study undergoing surgery or interventions, it remains to be investigated whether or at which concentrations the bleeding risk is increased when baseline levels are within prophylactic ranges.