Hereditary Factor X (FX) Deficiency (FXD) leads to bleeds. Therapy is based on treating (episodic) or avoiding (prophylaxis) bleeds with procoagulants.

We aimed to evaluate the efficacy/effectiveness and safety of prophylaxis against bleeds in people with FXD (PwFXD) compared to exclusive episodic treatment or prophylaxis with a different procoagulant.

We performed a systematic review based on a database-specific strategic search. Two reviewers blindly selected the publications according to the research question. In addition, prophylaxis-referenced citations from all the included publications and from the excluded reviews published since 2014 were evaluated for eligibility. Efficiency was evaluated as bleeding- related outcomes. Quality and risk of bias were assessed using the Joanna Briggs Institute checklists. (CRD42024535021).

Sixteen publications involving 76 PwFXD on prophylaxis were included, comprising quasi-experimental (3 [19%]/35 PwFXD [46%]), cohort (2 [12%]/21 PwFXD [27%]), and case reports (11 [69%]/20 PwFXD [26%]). Interventional prophylactic procoagulants were prothrombin complex concentrate (9 publications), plasma-derived FX (6 publications), and plasma-derived factor IX (1 publication). Individual annualized bleeding rates (iABR) ranged from 0 to 2.2 (n=13 publications). Thirty PwFXD with zero bleed were reported. Among controls, all 16 publications reported bleeding, with iABR ranging from 2.4 to 136.8 (6 publications). Two PwFXD had zero bleed. Only 2 (18%) case reports met high-quality criteria; no cohort or quasi-experimental study had high-quality.

Most publications and authors formed a connected citation network, indicating collaborative efforts and shared research focus in FXD prophylaxis. Prophylaxis in PwFXD was described as more effective than episodic treatment. However, best designed studies based on well-defined outcomes are required to certify this evidence.