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.