Pediatric severe factor XI deficiency: A multicenter study

Abstract

Background Factor XI (FXI) deficiency is a rare autosomal recessive bleeding disorder. Only scarce publications address its clinical features in children. The increased prevalence of FXI deficiency in Israel enabled data collection for this large multicenter cohort study. Objective Some hemostatic challenges may be unique or more common in children, such as bleeding in the neonatal period or trauma‐related injury. The current study was designed to explore the potential impact of these differences in children with severe FXI deficiency. Methods Medical files of all children with FXI level under 15% followed at five tertiary centers were evaluated. The retrieved data comprised demographic and clinical characteristics, including bleeding episodes, surgical interventions, treatment strategies, as well as laboratory features. Results Sixty children, whose median age at diagnosis was 4.2 years and their median FXI level was 4%, were included. Three children experienced triggered intracranial hemorrhage (ICH) and two children had major bleeds. No bleeding complications occurred in surgeries in which hemostatic treatment consisting mostly of tranexamic acid or fresh frozen plasma was applied (n = 45). In contrast, excessive bleeding was noted in 25% of surgical procedures performed without hemostatic preparation (p = .002). Conclusion This study's findings confirm the generally favorable outcome of this rare bleeding disorder, with no spontaneous bleeds or cases of perinatal ICH. Nonetheless, proper diagnosis and adequate hemostasis in the surgical setting are imperative. Unlike previous studies in adults, our pediatric study suggests an association between the severity of FXI deficiency and bleeding tendency.

Cerebral sinus venous thrombosis in children with inherited bleeding disorders: A case series

“…23 A large multicenter cohort study reported that in children with severe FXI deficiency and ICH, plasma infusion is the mainstay of therapy, and recombinant FVII may be considered for patients with levels <1% due to risk of FXI inhibitor development. 22,23 FXI levels >30% are considered hemostatic, especially in patients undergoing surgery. 23 While the development of CSVT in children with inherited BDs is uncommon, the management of such thrombi are based on adult experiences, indicating that short-duration anticoagulation with concurrent factor prophylaxis may be feasible with close monitoring of factor levels and intracranial imaging.…”

“…22,23 FXI levels >30% are considered hemostatic, especially in patients undergoing surgery. 23 While the development of CSVT in children with inherited BDs is uncommon, the management of such thrombi are based on adult experiences, indicating that short-duration anticoagulation with concurrent factor prophylaxis may be feasible with close monitoring of factor levels and intracranial imaging. 5,24 Pediatric studies in CSVT following trauma with ICH indicate that anticoagulation therapy may be safe with close monitoring and without worsening of ICH, although as mentioned in pediatric CHEST guidelines, withholding anticoagulation therapy with watchful waiting and imaging surveillance is an appropriate alternative in certain cases, as thrombi can resolve spontaneously due to physiologic processes including fibrinolysis.…”

“…Patients with FXI deficiency present a variable phenotype, with bleeding seen mainly post‐surgery/trauma, and severe bleeds such as ICH being extremely rare 23 . A large multicenter cohort study reported that in children with severe FXI deficiency and ICH, plasma infusion is the mainstay of therapy, and recombinant FVII may be considered for patients with levels <1% due to risk of FXI inhibitor development 22,23 . FXI levels >30% are considered hemostatic, especially in patients undergoing surgery 23 …”