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Numerous recent reports have described the use of recombinant factor VIIa (rFVIIa) in non-hemophilia bleeding Situations for achievement of hemostasis. However, its use in clinical situations other than hemophilia patients with inhibitors has been complicated by some reports of thrombotic events. rFVIIa has been used successfully to treat coagulopathic and/or bleeding neonates. The prevalence of thrombotic events in these neonates is completely unknown. This study was initiated to determine the risk of thrombotic events associated with rFVIIa use in neonates. Procedure. All published literature in non-hemophilic, non-congenital factor VII deficient neonates receiving rFVIIa was reviewed. In addition, all data submitted to the SeveN Bleep Registry, a web-based registry of rFVIIa uses in non-hemophilic children was analyzed.

X-linked neutropenia (XLN, OMIM #300299) is a rare form of severe congenital neutropenia. It was originally described in a three-generation family with five affected members that had an L270P mutation in the GTP-ase binding domain (GBD) of the Wiskott-Aldrich syndrome protein (WASP) [Devriendt et al (2001) Nature Genetics, Vol. 27, 313-317]. Here, we report and describe a large three-generation family with XLN, with 10 affected males and eight female carriers. A c.882T>C mutation was identified in the WAS gene, resulting in an I294T mutation. The infectious course is variable and mild in view of the profound neutropenia. In addition to the original description, low-normal IgA levels, low to low-normal platelet counts and reduced natural killer (NK)-cell counts also appear as consistent XLN features. However, inverted CD4/CD8 ratios were not found in this family, nor were cases identified with myelodysplastic syndrome or acute myeloid leukaemia. Female carriers exhibited a variable attenuated phenotype. Like L270P WASP, I294T WASP is constitutively active towards actin polymerization. In conclusion, this largest XLN kindred identified to date provides new independent genetic evidence that mutations disrupting the auto-inhibitory GBD of WASP are the cause of XLN. Reduced NK cells, low to low normal platelet counts and low to low-normal IgA levels are also features of XLN.