Nephrotic syndrome (NS) is a pathological state of the glomerular filtration barrier associated with an increased venous and arterial thrombotic risk. Current guidelines suggest heparin-based or vitamin K antagonist (VKA) regimens for thromboprophylaxis in such patients. Although widely prescribed for other indications, direct oral anticoagulants (DOACs) are not recommended in NS because of limited pharmacological and safety reports. This study aimed to compare DOACs and VKAs for thromboprophylaxis in NS, specifically regarding thrombotic events (TEs) and bleeding events (BEs).

We conducted a retrospective monocentric analysis of recorded NS episodes that required prophylactic anticoagulation between January 2006 and December 2023. We included 133 NS episodes of which 51 were treated with DOACs and 82 with VKAs. The primary endpoint was a composite endpoint, including thrombosis occurrence and major or clinically significant BEs during thromboprophylaxis. The secondary endpoints consisted of relevant features potentially involved when each primary endpoint was considered independently.

Patient characteristics, underlying NS etiology, personal thrombotic and bleeding risk factors, and biological parameters were globally similar in both groups. The primary endpoint appeared similar in both groups ( = 0.481). The secondary endpoints were mostly hypothesis-generating because of the low TE ( = 2) and BE ( = 7) occurrences.

This study provides reassuring clinical data on DOAC use in NS thromboprophylaxis compared with VKAs, the recommended therapy, and calls for confirmation in randomized controlled trials (RCTs) and larger pharmacological studies.