Discussion
We present four pediatric patients with BDs and CSVT, which required balancing the need for hemostasis in the setting of an intracranial/abdominal bleed while avoiding the propagation of CSVT. Thrombus development in patients with inherited BDs most commonly occurs due to the presence of a central venous catheter, iatrogenic development due to factor therapy, or presence of underlying prothrombotic gene mutations 9. The development of CSVT following a closed head injury is uncommon but can occur in the presence of a skull fracture or hematoma that leads to compression of the cerebral sinuses10,11.There is currently no literature addressing the presence or management of a post-traumatic CSVT in pediatric patients with inherited BDs.
Standard guidelines that direct management of thromboembolism in children with hemophilia are lacking1. Many factors should be taken into account when anticoagulating a patient with hemophilia, including the severity of bleeding and thrombosis, and the type and duration of anticoagulant therapy. When using easily reversible anticoagulants while maintaining FVIII/FIX levels >30%, anticoagulation has been found to be safe in hemophilia, with some reports recommending shorter duration of 6 to 8 weeks for provoked thrombosis while others employing the “shortest duration” necessary until thrombus resolution 1,12.
Reports of thrombus development in patients with VWD including type 3 VWD, are rare 13. VWF concentrates have been shown to contribute to thrombus development in patients with VWD14. It is possible that in our patient with type 3 VWD, VWF concentrate, along with trauma, was a contributing factor in thrombus formation. This may be supported by the fact that upon cessation of VWF concentrate, CSVT improved within 3 days, with complete resolution within a month despite no anticoagulation therapy. Notably, with administration of VWF concentrate, levels of VWF and FVIII:C should be monitored to guide treatment and avoid supratherapeutic levels that may increase the risk for thrombosis15.
FXI demonstrates properties as a procoagulant and inhibits fibrinolysis whereas deficiency has been found to provide protection against thrombus formation in animal models and humans 16,17. Moreover, inhibition of FXI has been shown to serve as effective thromboprophylaxis18. For these reasons, it is plausible that low levels of FXI in patient 3 facilitated thrombus resolution despite no anticoagulation.
While the development of CSVT in children with inherited BDs is uncommon, the management of such thrombi are based on adult experience indicating that short duration anticoagulation with concurrent factor prophylaxis may be feasible with close monitoring of factor levels and intracranial imaging 19,20. As patients 2, 3, and 4 had CSVT resolution without anticoagulation, watchful observation may be an alternative approach for managing CSVT in these patients, especially in the setting of ICH, and anticoagulation reserved for worsening clinical and/or imaging findings of CSVT. 6. Prospective studies are required to determine the risks and outcomes associated with withholding versus administering anticoagulation therapy in pediatric patients with inherited BDs and CSVT.