Background: Thrombotic events in congenital factor (F)XIII deficiency are extremely rare. To our knowledge, we describe the first case of severe congenital FXIII deficiency associated with recurrent venous thrombotic events.

Key clinician question: How to deal with anticoagulation treatment in patients with severe FXIII deficiency?

Clinical approach: The patient was treated with rivaroxaban and plasma-derived FXIII substitution therapy as prophylaxis without bleeding complications. We aimed at FXIII trough levels of 50% during the loading doses of rivaroxaban, then 30% during the maintenance dose of rivaroxaban, and finally 20% during the long-term use of prophylactic dose of rivaroxaban.

Conclusion: Treatment of thrombotic events with rivaroxaban in patients with severe bleeding disorders seems to be safe, requiring an adaptation of the intensity of the replacement therapy.